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Zhang, Xianwen, Yuhan Li, Yingyi Cao, Ying Wu i Gong Cheng. "The Role of Noncoding RNA in the Transmission and Pathogenicity of Flaviviruses". Viruses 16, nr 2 (2.02.2024): 242. http://dx.doi.org/10.3390/v16020242.
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Noncoding RNAs (ncRNAs) constitute a class of RNA molecules that lack protein-coding capacity. ncRNAs frequently modulate gene expression through specific interactions with target proteins or messenger RNAs, thereby playing integral roles in a wide array of cellular processes. The Flavivirus genus comprises several significant members, such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV), which have caused global outbreaks, resulting in high morbidity and mortality in human populations. The life cycle of arthropod-borne flaviviruses encompasses their transmission between hematophagous insect vectors and mammalian hosts. During this process, a complex three-way interplay occurs among the pathogen, vector, and host, with ncRNAs exerting a critical regulatory influence. ncRNAs not only constitute a crucial regulatory mechanism that has emerged from the coevolution of viruses and their hosts but also hold potential as antiviral targets for controlling flavivirus epidemics. This review introduces the biogenesis of flavivirus-derived ncRNAs and summarizes the regulatory roles of ncRNAs in viral replication, vector-mediated viral transmission, antiviral innate immunity, and viral pathogenicity. A profound comprehension of the interplay between ncRNAs and flaviviruses will help formulate efficacious prophylactic and therapeutic strategies against flavivirus-related diseases.
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Habarugira, Gervais, Jasmin Moran, Jessica J. Harrison, Sally R. Isberg, Jody Hobson-Peters, Roy A. Hall i Helle Bielefeldt-Ohmann. "Evidence of Infection with Zoonotic Mosquito-Borne Flaviviruses in Saltwater Crocodiles (Crocodylus porosus) in Northern Australia". Viruses 14, nr 5 (21.05.2022): 1106. http://dx.doi.org/10.3390/v14051106.
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The risk of flavivirus infections among the crocodilian species was not recognised until West Nile virus (WNV) was introduced into the Americas. The first outbreaks caused death and substantial economic losses in the alligator farming industry. Several other WNV disease episodes have been reported in crocodilians in other parts of the world, including Australia and Africa. Considering that WNV shares vectors with other flaviviruses, crocodilians are highly likely to also be exposed to flaviviruses other than WNV. A serological survey for flaviviral infections was conducted on saltwater crocodiles (Crocodylus porosus) at farms in the Northern Territory, Australia. Five hundred serum samples, collected from three crocodile farms, were screened using a pan-flavivirus-specific blocking ELISA. The screening revealed that 26% (n = 130/500) of the animals had antibodies to flaviviruses. Of these, 31.5% had neutralising antibodies to WNVKUN (Kunjin strain), while 1.5% had neutralising antibodies to another important flavivirus pathogen, Murray Valley encephalitis virus (MVEV). Of the other flaviviruses tested for, Fitzroy River virus (FRV) was the most frequent (58.5%) in which virus neutralising antibodies were detected. Our data indicate that farmed crocodiles in the Northern Territory are exposed to a range of potentially zoonotic flaviviruses, in addition to WNVKUN. While these flaviviruses do not cause any known diseases in crocodiles, there is a need to investigate whether infected saltwater crocodiles can develop a viremia to sustain the transmission cycle or farmed crocodilians can be used as sentinels to monitor the dynamics of arboviral infections in tropical areas.
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Göertz, G. P., J. J. Fros, P. Miesen, C. B. F. Vogels, M. L. van der Bent, C. Geertsema, C. J. M. Koenraadt, R. P. van Rij, M. M. van Oers i G. P. Pijlman. "Noncoding Subgenomic Flavivirus RNA Is Processed by the Mosquito RNA Interference Machinery and Determines West Nile Virus Transmission by Culex pipiens Mosquitoes". Journal of Virology 90, nr 22 (31.08.2016): 10145–59. http://dx.doi.org/10.1128/jvi.00930-16.
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ABSTRACT Flaviviruses, such as Zika virus, yellow fever virus, dengue virus, and West Nile virus (WNV), are a serious concern for human health. Flaviviruses produce an abundant noncoding subgenomic flavivirus RNA (sfRNA) in infected cells. sfRNA results from stalling of the host 5′-3′ exoribonuclease XRN1/Pacman on conserved RNA structures in the 3′ untranslated region (UTR) of the viral genomic RNA. sfRNA production is conserved in insect-specific, mosquito-borne, and tick-borne flaviviruses and flaviviruses with no known vector, suggesting a pivotal role for sfRNA in the flavivirus life cycle. Here, we investigated the function of sfRNA during WNV infection of Culex pipiens mosquitoes and evaluated its role in determining vector competence. An sfRNA1-deficient WNV was generated that displayed growth kinetics similar to those of wild-type WNV in both RNA interference (RNAi)-competent and -compromised mosquito cell lines. Small-RNA deep sequencing of WNV-infected mosquitoes indicated an active small interfering RNA (siRNA)-based antiviral response for both the wild-type and sfRNA1-deficient viruses. Additionally, we provide the first evidence that sfRNA is an RNAi substrate in vivo . Two reproducible small-RNA hot spots within the 3′ UTR/sfRNA of the wild-type virus mapped to RNA stem-loops SL-III and 3′ SL, which stick out of the three-dimensional (3D) sfRNA structure model. Importantly, we demonstrate that sfRNA-deficient WNV displays significantly decreased infection and transmission rates in vivo when administered via the blood meal. Finally, we show that transmission and infection rates are not affected by sfRNA after intrathoracic injection, thereby identifying sfRNA as a key driver to overcome the mosquito midgut infection barrier. This is the first report to describe a key biological function of sfRNA for flavivirus infection of the arthropod vector, providing an explanation for the strict conservation of sfRNA production. IMPORTANCE Understanding the flavivirus transmission cycle is important to identify novel targets to interfere with disease and to aid development of virus control strategies. Flaviviruses produce an abundant noncoding viral RNA called sfRNA in both arthropod and mammalian cells. To evaluate the role of sfRNA in flavivirus transmission, we infected mosquitoes with the flavivirus West Nile virus and an sfRNA-deficient mutant West Nile virus. We demonstrate that sfRNA determines the infection and transmission rates of West Nile virus in Culex pipiens mosquitoes. Comparison of infection via the blood meal versus intrathoracic injection, which bypasses the midgut, revealed that sfRNA is important to overcome the mosquito midgut barrier. We also show that sfRNA is processed by the antiviral RNA interference machinery in mosquitoes. This is the first report to describe a pivotal biological function of sfRNA in arthropods. The results explain why sfRNA production is evolutionarily conserved.
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Cook, Shelley, Shannon N. Bennett, Edward C. Holmes, Reine De Chesse, Gregory Moureau i Xavier de Lamballerie. "Isolation of a new strain of the flavivirus cell fusing agent virus in a natural mosquito population from Puerto Rico". Journal of General Virology 87, nr 4 (1.04.2006): 735–48. http://dx.doi.org/10.1099/vir.0.81475-0.
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The genus Flavivirus contains approximately 70 single-stranded, positive-sense RNA viruses that are mosquito-borne, tick-borne or have no known vector. Two discoveries support previous suggestions of the existence of a large number of unsampled flaviviruses: (i) a new flavivirus, Kamiti River virus, was recently isolated from Kenyan mosquitoes, and (ii) sequences with high similarity to those of flaviviruses have been found integrated into the genome of Aedes mosquitoes, suggesting a past infection with a virus (or viruses) that has yet to be discovered. These sequences were related most closely to a flavivirus that infects insects alone, cell fusing agent virus (CFAV). CFAV was originally isolated in the laboratory from an Aedes aegypti cell line. To date, this virus had not been found in the wild. In the present study, over 40 isolates of a novel strain of CFAV were discovered from mature mosquitoes sampled from the wild in Puerto Rico. The viral strain was present in a range of mosquito species, including Aedes aegypti, Aedes albopictus and Culex sp., from numerous locations across the island and, importantly, in mosquitoes of both sexes, suggesting vertical transmission. Here, results from viral screening, and cell culture and molecular identification of the infected mosquitoes are presented. Experimental-infection tests were also conducted by using the original CFAV strain and a highly efficient reverse-transcription mechanism has been documented, in which initiation of copying occurs at the 3′ terminus of either the genomic RNA or the intermediate of replication, potentially elucidating the mechanism by which flaviviral sequences may have integrated into mosquito genomes.
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Vasilakis, Nikos, i Scott C. Weaver. "Flavivirus transmission focusing on Zika". Current Opinion in Virology 22 (luty 2017): 30–35. http://dx.doi.org/10.1016/j.coviro.2016.11.007.
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Wang, Hong-Jiang, Xiao-Feng Li, Long Liu, Yan-Peng Xu, Qing Ye, Yong-Qiang Deng, Xing-Yao Huang i in. "The Emerging Duck Flavivirus Is Not Pathogenic for Primates and Is Highly Sensitive to Mammalian Interferon Antiviral Signaling". Journal of Virology 90, nr 14 (4.05.2016): 6538–48. http://dx.doi.org/10.1128/jvi.00197-16.
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ABSTRACTFlaviviruses pose a significant threat to both animals and humans. Recently, a novel flavivirus, duck Tembusu virus (DTMUV), was identified to be the causative agent of a serious duck viral disease in Asia. Its rapid spread, expanding host range, and uncertain transmission routes have raised substantial concerns regarding its potential threats to nonavian hosts, including humans. Here, we demonstrate that DTMUV is not pathogenic for nonhuman primates and is highly sensitive to mammal type I interferon (IFN) signaling.In vitroassays demonstrated that DTMUV infected and replicated efficiently in various mammalian cell lines. Further tests in mice demonstrated high neurovirulence and the age-dependent neuroinvasiveness of the virus. In particular, the inoculation of DTMUV into rhesus monkeys did not result in either viremia or apparent clinical symptoms, although DTMUV-specific humoral immune responses were detected. Furthermore, we revealed that although avian IFN failed to inhibit DTMUV in avian cells, DTMUV was more sensitive to the antiviral effects of type I interferon than other known human-pathogenic flaviviruses. Knockout of the type I IFN receptor in mice caused apparent viremia, viscerotropic disease, and mortality, indicating a vital role of IFN signaling in protection against DTMUV infection. Collectively, we provide direct experimental evidence that this novel avian-origin DTMUV possesses a limited capability to establish infection in immunocompetent primates due to its decreased antagonistic activity in the mammal IFN system. Furthermore, our findings highlight the potential risk of DTMUV infection in immunocompromised individuals and warrant studies on the cross-species transmission and pathogenesis of this novel flavivirus.IMPORTANCEMosquito-borne flaviviruses comprise a large group of pathogenic and nonpathogenic members. The pathogenic flaviviruses include dengue, West Nile, and Japanese encephalitis viruses, and the nonpathogenic flaviviruses normally persist in a natural cycle and rarely cause disease in humans. A novel flavivirus, DTMUV (also known as duck egg drop syndrome flavivirus [DEDSV]) was identified in 2012 in ducks and then rapidly spread to several Asian countries. This new flavivirus was then shown to infect multiple avian species, resulting in neurological symptoms with unknown routes of transmission. There is public concern regarding its potential transmission from birds to humans and other nonavian hosts. Our present study shows that the mammalian IFN system can efficiently eliminate DTMUV infection and that the emergence of severe DTMUV-associated disease in mammals, especially humans, is unlikely. Currently, DTMUV infection mostly affects avian species.
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Göertz, Giel P., Joyce W. M. van Bree, Anwar Hiralal, Bas M. Fernhout, Carmen Steffens, Sjef Boeren, Tessa M. Visser i in. "Subgenomic flavivirus RNA binds the mosquito DEAD/H-box helicase ME31B and determines Zika virus transmission by Aedes aegypti". Proceedings of the National Academy of Sciences 116, nr 38 (5.09.2019): 19136–44. http://dx.doi.org/10.1073/pnas.1905617116.
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Zika virus (ZIKV) is an arthropod-borne flavivirus predominantly transmitted by Aedes aegypti mosquitoes and poses a global human health threat. All flaviviruses, including those that exclusively replicate in mosquitoes, produce a highly abundant, noncoding subgenomic flavivirus RNA (sfRNA) in infected cells, which implies an important function of sfRNA during mosquito infection. Currently, the role of sfRNA in flavivirus transmission by mosquitoes is not well understood. Here, we demonstrate that an sfRNA-deficient ZIKV (ZIKVΔSF1) replicates similar to wild-type ZIKV in mosquito cell culture but is severely attenuated in transmission by Ae. aegypti after an infectious blood meal, with 5% saliva-positive mosquitoes for ZIKVΔSF1 vs. 31% for ZIKV. Furthermore, viral titers in the mosquito saliva were lower for ZIKVΔSF1 as compared to ZIKV. Comparison of mosquito infection via infectious blood meals and intrathoracic injections showed that sfRNA is important for ZIKV to overcome the mosquito midgut barrier and to promote virus accumulation in the saliva. Next-generation sequencing of infected mosquitoes showed that viral small-interfering RNAs were elevated upon ZIKVΔSF1 as compared to ZIKV infection. RNA-affinity purification followed by mass spectrometry analysis uncovered that sfRNA specifically interacts with a specific set of Ae. aegypti proteins that are normally associated with RNA turnover and protein translation. The DEAD/H-box helicase ME31B showed the highest affinity for sfRNA and displayed antiviral activity against ZIKV in Ae. aegypti cells. Based on these results, we present a mechanistic model in which sfRNA sequesters ME31B to promote flavivirus replication and virion production to facilitate transmission by mosquitoes.
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AYADI, T., A. HAMMOUDA, A. POUX, T. BOULINIER, S. LECOLLINET i S. SELMI. "Evidence of exposure of laughing doves (Spilopelia senegalensis) to West Nile and Usutu viruses in southern Tunisian oases". Epidemiology and Infection 145, nr 13 (14.08.2017): 2808–16. http://dx.doi.org/10.1017/s0950268817001789.
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SUMMARYIt has previously been suggested that southern Tunisian oases may be suitable areas for the circulation of flaviviruses. In order to anticipate and prevent possible epidemiological spread of flaviviruses in humans and domestic animals, the ecology of their transmission in the oasis system needs to be better understood. Thus, the aim of this study was to assess the seroprevalence of anti-flavivirus antibodies in the laughing dove (Spilopelia senegalensis), an abundant resident bird in Tunisian oases. Anti-flavivirus antibodies were detected in 17% of sampled doves. Ten per cent of the total tested doves were West Nile virus (WNV) seropositive and 4% were Usutu virus (USUV) seropositive, which provides the first evidence of USUV circulation in Tunisian birds. We also found that the occurrence probability of anti-flavivirus antibodies in dove plasma increased with decreasing distance to coast, suggesting that doves inhabiting coastal oases were more exposed to flaviviruses compared with those inhabiting inland oases. We also found significantly higher antibody occurrence probability in adult doves compared with young doves, which underlines the effect of exposure time. Overall, our results suggest that the laughing dove may be used for WNV and USUV surveillance in southern Tunisia. They also stress the need for investigations combining data on birds and mosquitoes to better understand the ecological factors governing the circulation of flaviviruses in this area.
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Williams, Richard A. J., Hillary A. Criollo Valencia, Irene López Márquez, Fernando González González, Francisco Llorente, Miguel Ángel Jiménez-Clavero, Núria Busquets, Marta Mateo Barrientos, Gustavo Ortiz-Díez i Tania Ayllón Santiago. "West Nile Virus Seroprevalence in Wild Birds and Equines in Madrid Province, Spain". Veterinary Sciences 11, nr 6 (7.06.2024): 259. http://dx.doi.org/10.3390/vetsci11060259.
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West Nile virus (WNV) is a re-emerging flavivirus, primarily circulating among avian hosts and mosquito vectors, causing periodic outbreaks in humans and horses, often leading to neuroinvasive disease and mortality. Spain has reported several outbreaks, most notably in 2020 with seventy-seven human cases and eight fatalities. WNV has been serologically detected in horses in the Community of Madrid, but to our knowledge, it has never been reported from wild birds in this region. To estimate the seroprevalence of WNV in wild birds and horses in the Community of Madrid, 159 wild birds at a wildlife rescue center and 25 privately owned equines were sampled. Serum from thirteen birds (8.2%) and one equine (4.0%) tested positive with a WNV competitive enzyme-linked immunosorbent assay (cELISA) designed for WNV antibody detection but sensitive to cross-reacting antibodies to other flaviviruses. Virus-neutralization test (VNT) confirmed WNV antibodies in four bird samples (2.5%), and antibodies to undetermined flavivirus in four additional samples. One equine sample (4.0%) tested positive for WNV by VNT, although this horse previously resided in a WN-endemic area. ELISA-positive birds included both migratory and resident species, juveniles and adults. Two seropositive juvenile birds suggest local flavivirus transmission within the Community of Madrid, while WNV seropositive adult birds may have been infected outside Madrid. The potential circulation of flaviviruses, including WNV, in birds in the Madrid Community raises concerns, although further surveillance of mosquitoes, wild birds, and horses in Madrid is necessary to establish the extent of transmission and the principal species involved.
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Reyes-Ruiz, José Manuel, Juan Fidel Osuna-Ramos, Luis Adrián De Jesús-González, Selvin Noé Palacios-Rápalo, Carlos Daniel Cordero-Rivera, Carlos Noe Farfan-Morales, Arianna Mahely Hurtado-Monzón i in. "The Regulation of Flavivirus Infection by Hijacking Exosome-Mediated Cell–Cell Communication: New Insights on Virus–Host Interactions". Viruses 12, nr 7 (16.07.2020): 765. http://dx.doi.org/10.3390/v12070765.
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The arthropod-borne flaviviruses are important human pathogens, and a deeper understanding of the virus–host cell interaction is required to identify cellular targets that can be used as therapeutic candidates. It is well reported that the flaviviruses hijack several cellular functions, such as exosome-mediated cell communication during infection, which is modulated by the delivery of the exosomal cargo of pro- or antiviral molecules to the receiving host cells. Therefore, to study the role of exosomes during flavivirus infections is essential, not only to understand its relevance in virus–host interaction, but also to identify molecular factors that may contribute to the development of new strategies to block these viral infections. This review explores the implications of exosomes in flavivirus dissemination and transmission from the vector to human host cells, as well as their involvement in the host immune response. The hypothesis about exosomes as a transplacental infection route of ZIKV and the paradox effect or the dual role of exosomes released during flavivirus infection are also discussed here. Although several studies have been performed in order to identify and characterize cellular and viral molecules released in exosomes, it is not clear how all of these components participate in viral pathogenesis. Further studies will determine the balance between protective and harmful exosomes secreted by flavivirus infected cells, the characteristics and components that distinguish them both, and how they could be a factor that determines the infection outcome.
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Delfin-Riela, Triana, Martín Rossotti, Romina Alvez-Rosado, Carmen Leizagoyen i Gualberto González-Sapienza. "Highly Sensitive Detection of Zika Virus Nonstructural Protein 1 in Serum Samples by a Two-Site Nanobody ELISA". Biomolecules 10, nr 12 (9.12.2020): 1652. http://dx.doi.org/10.3390/biom10121652.
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The Zika virus was introduced in Brazil in 2015 and, shortly after, spread all over the Americas. Nowadays, it remains present in more than 80 countries and represents a major threat due to some singularities among other flaviviruses. Due to its easy transmission, high percentage of silent cases, the severity of its associated complications, and the lack of prophylactic methods and effective treatments, it is essential to develop reliable and rapid diagnostic tests for early containment of the infection. Nonstructural protein 1 (NS1), a glycoprotein involved in all flavivirus infections, is secreted since the beginning of the infection into the blood stream and has proven to be a valuable biomarker for the early diagnosis of other flaviviral infections. Here, we describe the development of a highly sensitive nanobody ELISA for the detection of the NS1 protein in serum samples. Nanobodies were selected from a library generated from a llama immunized with Zika NS1 (ZVNS1) by a two-step high-throughput screening geared to identify the most sensitive and specific nanobody pairs. The assay was performed with a sub-ng/mL detection limit in the sera and showed excellent reproducibility and accuracy when validated with serum samples spiked with 0.80, 1.60, or 3.10 ng/mL of ZVNS1. Furthermore, the specificity of the developed ELISA was demonstrated using a panel of flavivirus’ NS1 proteins; this is of extreme relevance in countries endemic for more than one flavivirus. Considering that the nanobody sequences are provided, the assay can be reproduced in any laboratory at low cost, which may help to strengthen the diagnostic capacity of the disease even in low-resource countries.
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Peinado, Stephen A., Matthew T. Aliota, Bradley J. Blitvich i Lyric C. Bartholomay. "Biology and Transmission Dynamics of Aedes flavivirus". Journal of Medical Entomology 59, nr 2 (22.01.2022): 659–66. http://dx.doi.org/10.1093/jme/tjab197.
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Abstract Aedes albopictus (Skuse) and Aedes aegypti (Linnaeus) (Diptera: Culicidae) mosquitoes transmit pathogenic arthropod-borne viruses, including dengue, chikungunya, and Zika viruses, with significant global health consequences. Both Ae. albopictus and Ae. aegypti also are susceptible to Aedes flavivirus (AEFV), an insect-specific flavivirus (ISF) first isolated in Japan from Ae. albopictus and Ae. flavopictus. ISFs infect only insect hosts and evidence suggests that they are maintained by vertical transmission. In some cases, ISFs interfere with pathogenic flavivirus infection, and may have potential use in disease control. We explored the host range of AEFV in 4 genera of mosquitoes after intrathoracic injection and observed greater than 95% prevalence in the species of Aedes and Toxorhynchites tested. Anopheles and Culex species were less permissive to infection. Vertical transmission studies revealed 100% transovarial transmission and a filial infection rate of 100% for AEFV in a persistently-infected colony of Ae. albopictus. Horizontal transmission potential was assessed for adult and larval mosquitoes following per os exposures and in venereal transmission experiments. No mosquitoes tested positive for AEFV infection after blood feeding, and infection with AEFV after sucrose feeding was rare. Similarly, 2% of adult mosquitoes tested positive for AEFV after feeding on infected cells in culture as larvae. Venereal transmission of AEFV was most frequently observed from infected males to uninfected females as compared with transmission from infected females to uninfected males. These results reveal new information on the infection potential of AEFV in mosquitoes and expand our understanding of both vertical and horizontal transmission of ISFs.
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Noden, Bruce H., Milka Musuuo, Larai Aku-Akai, Berta van der Colf, Israel Chipare i Rob Wilkinson. "Risk assessment of flavivirus transmission in Namibia". Acta Tropica 137 (wrzesień 2014): 123–29. http://dx.doi.org/10.1016/j.actatropica.2014.05.010.
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Troupin, Andrea, Crystal Grippin i Tonya M. Colpitts. "Flavivirus Pathogenesis in the Mosquito Transmission Vector". Current Clinical Microbiology Reports 4, nr 3 (13.07.2017): 115–23. http://dx.doi.org/10.1007/s40588-017-0066-6.
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Whelan, Jillian N., Nicholas A. Parenti, Joshua Hatterschide, David M. Renner, Yize Li, Hanako M. Reyes, Beihua Dong, Erick R. Perez, Robert H. Silverman i Susan R. Weiss. "Zika virus employs the host antiviral RNase L protein to support replication factory assembly". Proceedings of the National Academy of Sciences 118, nr 22 (24.05.2021): e2101713118. http://dx.doi.org/10.1073/pnas.2101713118.
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Infection with the flavivirus Zika virus (ZIKV) can result in tissue tropism, disease outcome, and route of transmission distinct from those of other flaviviruses; therefore, we aimed to identify host machinery that exclusively promotes the ZIKV replication cycle, which can inform on differences at the organismal level. We previously reported that deletion of the host antiviral ribonuclease L (RNase L) protein decreases ZIKV production. Canonical RNase L catalytic activity typically restricts viral infection, including that of the flavivirus dengue virus (DENV), suggesting an unconventional, proviral RNase L function during ZIKV infection. In this study, we reveal that an inactive form of RNase L supports assembly of ZIKV replication factories (RFs) to enhance infectious virus production. Compared with the densely concentrated ZIKV RFs generated with RNase L present, deletion of RNase L induced broader subcellular distribution of ZIKV replication intermediate double-stranded RNA (dsRNA) and NS3 protease, two constituents of ZIKV RFs. An inactive form of RNase L was sufficient to contain ZIKV genome and dsRNA within a smaller RF area, which subsequently increased infectious ZIKV release from the cell. Inactive RNase L can interact with cytoskeleton, and flaviviruses remodel cytoskeleton to construct RFs. Thus, we used the microtubule-stabilization drug paclitaxel to demonstrate that ZIKV repurposes RNase L to facilitate the cytoskeleton rearrangements required for proper generation of RFs. During infection with flaviviruses DENV or West Nile Kunjin virus, inactive RNase L did not improve virus production, suggesting that a proviral RNase L role is not a general feature of all flavivirus infections.
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Sakkas, Hercules, Petros Bozidis, Xenofon Giannakopoulos, Nikolaos Sofikitis i Chrissanthy Papadopoulou. "An Update on Sexual Transmission of Zika Virus". Pathogens 7, nr 3 (3.08.2018): 66. http://dx.doi.org/10.3390/pathogens7030066.
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Zika virus (ZIKV) is a single-stranded RNA virus belonging to the arthropod-borne flaviviruses (arboviruses) which are mainly transmitted by blood-sucking mosquitoes of the genus Aedes. ZIKV infection has been known to be rather asymptomatic or presented as febrile self-limited disease; however, during the last decade the manifestation of ZIKV infection has been associated with a variety of neuroimmunological disorders including Guillain–Barré syndrome, microcephaly and other central nervous system abnormalities. More recently, there is accumulating evidence about sexual transmission of ZIKV, a trait that has never been observed in any other mosquito-borne flavivirus before. This article reviews the latest information regarding the latter and emerging role of ZIKV, focusing on the consequences of ZIKV infection on the male reproductive system and the epidemiology of human-to-human sexual transmission.
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Goërtz, G. P., J. J. Fros, P. Miesen, C. B. Vogels, C. Geertsema, C. J. Koenraadt, R. P. van Rij, M. M. van Oers i G. P. Pijlman. "Non-coding RNA determines flavivirus transmission by mosquitoes". International Journal of Infectious Diseases 53 (grudzień 2016): 162. http://dx.doi.org/10.1016/j.ijid.2016.11.395.
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Porier, Danielle L., Sarah N. Wilson, Dawn I. Auguste, Andrew Leber, Sheryl Coutermarsh-Ott, Irving C. Allen, Clayton C. Caswell i in. "Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine". Vaccines 9, nr 10 (7.10.2021): 1142. http://dx.doi.org/10.3390/vaccines9101142.
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Vaccination remains critical for viral disease outbreak prevention and control, but conventional vaccine development typically involves trade-offs between safety and immunogenicity. We used a recently discovered insect-specific flavivirus as a vector in order to develop an exceptionally safe, flavivirus vaccine candidate with single-dose efficacy. To evaluate the safety and efficacy of this platform, we created a chimeric Zika virus (ZIKV) vaccine candidate, designated Aripo/Zika virus (ARPV/ZIKV). ZIKV has caused immense economic and public health impacts throughout the Americas and remains a significant public health threat. ARPV/ZIKV vaccination showed exceptional safety due to ARPV/ZIKV’s inherent vertebrate host-restriction. ARPV/ZIKV showed no evidence of replication or translation in vitro and showed no hematological, histological or pathogenic effects in vivo. A single-dose immunization with ARPV/ZIKV induced rapid and robust neutralizing antibody and cellular responses, which offered complete protection against ZIKV-induced morbidity, mortality and in utero transmission in immune-competent and -compromised murine models. Splenocytes derived from vaccinated mice demonstrated significant CD4+ and CD8+ responses and significant cytokine production post-antigen exposure. Altogether, our results further support that chimeric insect-specific flaviviruses are a promising strategy to restrict flavivirus emergence via vaccine development.
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Chevalier, Véronique, Maud Marsot, Sophie Molia, Harena Rasamoelina, René Rakotondravao, Miguel Pedrono, Steeve Lowenski, Benoit Durand, Sylvie Lecollinet i Cécile Beck. "Serological Evidence of West Nile and Usutu Viruses Circulation in Domestic and Wild Birds in Wetlands of Mali and Madagascar in 2008". International Journal of Environmental Research and Public Health 17, nr 6 (18.03.2020): 1998. http://dx.doi.org/10.3390/ijerph17061998.
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The geographical distribution and impact on animal and human health of both West Nile and Usutu viruses, two flaviviruses of the Japanese encephalitis complex, have been increasing during the past two decades. Both viruses circulate in Europe and Africa within a natural cycle between wild birds and mosquitoes, mainly from the Culex genus. We retrospectively analyzed sera from domestic and wild birds sampled in 2008 in two wetlands, namely the Inner Niger Delta, Mali, and the Lake Alaotra area, Madagascar. Sera were first tested using a commercial ID Screen West Nile Competition Multi-species ELISA kit. Then, positive sera and sera with insufficient volume for testing with ELISA were tested with a Microneutralization Test. In Mali, the observed seroprevalence in domestic birds was 28.5% [24.5; 32.8] 95%CI, 3.1 % [1.8; 5.2] 95%CI, 6.2% [3.4; 10.2] 95%CI and 9.8 % [7.3; 12.8] 95%CI, for West Nile virus (WNV), Usutu virus (USUV), undetermined flavivirus, and WNV/USUV respectively. Regarding domestic birds of Madagascar, the observed seroprevalence was 4.4 % [2.1; 7.9]95%CI for WNV, 0.9% [0.1; 3.1] 95%CI for USUV, 1.3% [0.5; 2.8] 95%CI for undetermined flavivirus, and null for WNV/USUV. Among the 150 wild birds sampled in Madagascar, two fulvous whistling-ducks (Dendrocygna bicolor) were positive for WNV and two for an undetermined flavivirus. One white-faced whistling-duck (Dendrocygna viduata) and one Hottentot teal (Spatula hottentota) were tested positive for USUV. African and European wetlands are linked by wild bird migrations. This first detection of USUV—as well as the confirmed circulation of WNV in domestic birds of two wetlands of Mali and Madagascar—emphasizes the need to improve the surveillance, knowledge of epidemiological patterns, and phylogenetic characteristics of flavivirus in Africa, particularly in areas prone to sustained, intense flavivirus transmission such as wetlands.
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Colmant, Agathe M. G., Jody Hobson-Peters, Teun A. P. Slijkerman, Jessica J. Harrison, Gorben P. Pijlman, Monique M. van Oers, Peter Simmonds, Roy A. Hall i Jelke J. Fros. "Insect-Specific Flavivirus Replication in Mammalian Cells Is Inhibited by Physiological Temperature and the Zinc-Finger Antiviral Protein". Viruses 13, nr 4 (29.03.2021): 573. http://dx.doi.org/10.3390/v13040573.
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The genus Flavivirus contains pathogenic vertebrate-infecting flaviviruses (VIFs) and insect-specific flaviviruses (ISF). ISF transmission to vertebrates is inhibited at multiple stages of the cellular infection cycle, via yet to be elucidated specific antiviral responses. The zinc-finger antiviral protein (ZAP) in vertebrate cells can bind CpG dinucleotides in viral RNA, limiting virus replication. Interestingly, the genomes of ISFs contain more CpG dinucleotides compared to VIFs. In this study, we investigated whether ZAP prevents two recently discovered lineage II ISFs, Binjari (BinJV) and Hidden Valley viruses (HVV) from replicating in vertebrate cells. BinJV protein and dsRNA replication intermediates were readily observed in human ZAP knockout cells when cultured at 34 °C. In ZAP-expressing cells, inhibition of the interferon response via interferon response factors 3/7 did not improve BinJV protein expression, whereas treatment with kinase inhibitor C16, known to reduce ZAP’s antiviral function, did. Importantly, at 34 °C, both BinJV and HVV successfully completed the infection cycle in human ZAP knockout cells evident from infectious progeny virus in the cell culture supernatant. Therefore, we identify vertebrate ZAP as an important barrier that protects vertebrate cells from ISF infection. This provides new insights into flavivirus evolution and the mechanisms associated with host switching.
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Bournez, Laure, Gérald Umhang, Eva Faure, Jean-Marc Boucher, Franck Boué, Elsa Jourdain, Mathieu Sarasa i in. "Exposure of Wild Ungulates to the Usutu and Tick-Borne Encephalitis Viruses in France in 2009–2014: Evidence of Undetected Flavivirus Circulation a Decade Ago". Viruses 12, nr 1 (19.12.2019): 10. http://dx.doi.org/10.3390/v12010010.
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Flaviviruses have become increasingly important pathogens in Europe over the past few decades. A better understanding of the spatiotemporal distribution of flaviviruses in France is needed to better define risk areas and to gain knowledge of the dynamics of virus transmission cycles. Serum samples from 1014 wild boar and 758 roe deer from 16 departments (administrative units) in France collected from 2009 to 2014 were screened for flavivirus antibodies using a competitive ELISA (cELISA) technique. Serum samples found to be positive or doubtful by cELISA were then tested for antibodies directed against West Nile virus (WNV), Usutu virus (USUV), Bagaza virus (BAGV), and tick-borne encephalitis/Louping ill viruses (TBEV/LIV) by microsphere immunoassays (except BAGV) and micro-neutralization tests. USUV antibodies were detected only in southeastern and southwestern areas. TBEV/LIV antibodies were detected in serum samples from eastern, southwestern and northern departments. The results indicate continuous circulation of USUV in southern France from 2009 to 2014, which was unnoticed by the French monitoring system for bird mortality. The findings also confirm wider distribution of TBEV in the eastern part of the country than of human clinical cases. However, further studies are needed to determine the tick-borne flavivirus responsible for the seroconversion in southwestern and northern France.
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Nava, Jose Angel Regla, Ying-Ting Wang, Camila R. Fontes-Garfias, Thasneem Syed, Andrew Gonzalez, Karla Viramontes, Kristen M. Valentine i in. "Zika virus evolution in the presence of dengue virus-elicited cross-reactive immunity". Journal of Immunology 204, nr 1_Supplement (1.05.2020): 249.7. http://dx.doi.org/10.4049/jimmunol.204.supp.249.7.
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Abstract Zika virus (ZIKV), belongs to Flavivirus, causes neurological disorders including Guillain Barré syndrome and fetal microcephaly, and is responsible for widespread epidemics in countries where other flaviviruses, such as dengue (DENV), and yellow fever viruses, are endemic. However, how the cross-reactive, pre-existing immunity impacts the evolution of flaviviruses is poorly understood. To mimic the natural transmission cycle of ZIKV between vertebrate (human) hosts with pre-existing flavivirus immunity and invertebrate hosts (mosquito), ZIKV was subjected to 10 alternating cycles of passaging between DENV-immune mice and mosquito cells. We identified two mutations in the passaged ZIKV strains- one in the NS2B gene (I39V), both after passage in DENV-naïve and DENV-immune mice, and a mutation in the E gene (T470M), only after passage in DENV-immune mice. These mutations increase ZIKV virulence and pathogenesis in non-pregnant and pregnant Ifnar1−/− mice and abrogate cross-protection mediated by the pre-existing DENV immunity. In addition, ZIKV strain with the I39V mutation was more virulent than the parental ZIKV strain in human fetal neural progenitor cells (NPCs), and ZIKV variants in position 39 of the NS2B protein were observed in recent clinical isolates of ZIKV. Our data thus identify a mutational hotspot in the ZIKV NS2B protein and a mutation in the ZIKV E protein that arose as a consequence of the pre-existing immune pressure. Our results uncover the evolutionary strategies by which ZIKV can become pathogenic in both DENV-naïve and DENV-immune populations. Mechanistic studies of evolution in the presence and absence of cross-reactive immunity will benefit the development of safe and efficient flavivirus vaccines.
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Chapagain, Subash, Prince Pal Singh, Khanh Le, David Safronetz, Heidi Wood i Uladzimir Karniychuk. "Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues". PLOS Neglected Tropical Diseases 16, nr 7 (29.07.2022): e0010656. http://dx.doi.org/10.1371/journal.pntd.0010656.
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Japanese encephalitis virus (JEV) is the emerging and geographically expanding flavivirus and the major causative agent of encephalitis in humans in Asia. There are risks of JEV introduction into the Americas given a large population of amplifying hosts—pigs and wild boars, and insect vectors—Culex mosquitoes. There are emerging concerns about vector-free ways of flavivirus transmission, for example sexual and transplacental Zika virus transmissions, which may change flavivirus epidemiology and expand the geographical range to territories with no insect vectors. It is unknown whether JEV has tropism in the female lower reproductive tract and the potential for sexual transmission in humans. While clinical outcomes of transplacental JEV infection are described in humans and pigs, cellular targets and tissue tropism in the upper reproductive tract are also unknown. Here, we studied JEV infection phenotypes and host transcriptional responses in human reproductive epithelial cells. We found that JEV caused persistent infection and cytopathology in the vaginal epithelium, endometrial epithelium, and trophoblast. Human vaginal epithelial cells infected with JEV had altered transcriptional responses associated with inflammation and disruption of epithelial barrier function. Also, using pigs—the native amplifying host for JEV, we confirmed JEV tropism in the female lower and upper reproductive tracts. We discovered that JEV persists in the vaginal mucosa for at least 28 days and pigs shed the virus in vaginal secretions. We also found JEV persistence in the endometrium and placenta with transplacental and fetal infections. Altogether, we discovered that JEV targets the vaginal epithelium and has the potential for sexual transmission in humans. We also contributed to a better understanding of JEV pathogenesis during transplacental infection. Further studies are needed to better understand the interactions of JEV with reproductive tissues, how persistent infection affects female reproductive functions, and the risks for non-vector transmission.
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Zepeda, Omar, Daniel O. Espinoza, Evelin Martinez, Kaitlyn A. Cross, Sylvia Becker-Dreps, Aravinda M. de Silva, Natalie M. Bowman i in. "Antibody Immunity to Zika Virus among Young Children in a Flavivirus-Endemic Area in Nicaragua". Viruses 15, nr 3 (21.03.2023): 796. http://dx.doi.org/10.3390/v15030796.
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Objective: To understand the dynamics of Zika virus (ZIKV)-specific antibody immunity in children born to mothers in a flavivirus-endemic region during and after the emergence of ZIKV in the Americas. Methods: We performed serologic testing for ZIKV cross-reactive and type-specific IgG in two longitudinal cohorts, which enrolled pregnant women and their children (PW1 and PW2) after the beginning of the ZIKV epidemic in Nicaragua. Quarterly samples from children over their first two years of life and maternal blood samples at birth and at the end of the two-year follow-up period were studied. Results: Most mothers in this dengue-endemic area were flavivirus-immune at enrollment. ZIKV-specific IgG (anti-ZIKV EDIII IgG) was detected in 82 of 102 (80.4%) mothers in cohort PW1 and 89 of 134 (66.4%) mothers in cohort PW2, consistent with extensive transmission observed in Nicaragua during 2016. ZIKV-reactive IgG decayed to undetectable levels by 6–9 months in infants, whereas these antibodies were maintained in mothers at the year two time point. Interestingly, a greater contribution to ZIKV immunity by IgG3 was observed in babies born soon after ZIKV transmission. Finally, 43 of 343 (13%) children exhibited persistent or increasing ZIKV-reactive IgG at ≥9 months, with 10 of 30 (33%) tested demonstrating serologic evidence of incident dengue infection. Conclusions: These data inform our understanding of protective and pathogenic immunity to potential flavivirus infections in early life in areas where multiple flaviviruses co-circulate, particularly considering the immune interactions between ZIKV and dengue and the future possibility of ZIKV vaccination in women of childbearing potential. This study also shows the benefits of cord blood sampling for serologic surveillance of infectious diseases in resource-limited settings.
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Nguyen-Tien, Thang, Anh Ngoc Bui, Jiaxin Ling, Son Tran-Hai, Long Pham-Thanh, Vuong Nghia Bui, Tung Duy Dao i in. "The Distribution and Composition of Vector Abundance in Hanoi City, Vietnam: Association with Livestock Keeping and Flavivirus Detection". Viruses 13, nr 11 (16.11.2021): 2291. http://dx.doi.org/10.3390/v13112291.
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Background: Dengue virus and Japanese encephalitis virus are two common flaviviruses that are spread widely by Aedes and Culex mosquitoes. Livestock keeping is vital for cities; however, it can pose the risk of increasing the mosquito population. Our study explored how livestock keeping in and around a large city is associated with the presence of mosquitoes and the risk of them spreading flaviviruses. Methods: An entomological study was conducted in 6 districts with 233 households with livestock, and 280 households without livestock, in Hanoi city. BG-Sentinel traps and CDC light traps were used to collect mosquitoes close to animal farms and human habitats. Adult mosquitoes were counted, identified to species level, and grouped into 385 pools, which were screened for flaviviruses using a pan-flavivirus qPCR protocol and sequencing. Results: A total of 12,861 adult mosquitoes were collected at the 513 households, with 5 different genera collected, of which the Culex genus was the most abundant. Our study found that there was a positive association between livestock keeping and the size of the mosquito population—most predominantly between pig rearing and Culex species (p < 0.001). One pool of Cx. tritaeniorhynchus, collected in a peri-urban district, was found to be positive for Japanese encephalitis virus. Conclusions: The risk of flavivirus transmission in urban areas of Hanoi city due to the spread of Culex and Aedes mosquitoes could be facilitated by livestock keeping.
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Kushwaha, Nikhal, Vipin Kesharwani i Pankaj Kumar Jaiswal. "A GLOBAL CONCERN ON ZIKA VIRUS: TRANSMISSION, DIAGNOSIS, PREVENTION, AND TREATMENT". Journal of Drug Delivery and Therapeutics 8, nr 5 (11.09.2018): 136–40. http://dx.doi.org/10.22270/jddt.v8i5.1972.
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Zika virus is a mosquito-transmitted flavivirus belongs to family Flaviviridae which becomes the focus of an ongoing pandemic and public health emergency all around the world. Zika virus has two lineages African and Asian. Mosquito-borne flavivirus is thought to replicate initially in dendritic cell and then spread to lymph nodes and then to the bloodstream. Zika virus was initially recognized in Uganda in 1947 in Monkeys through a method that observed yellow fever. It was later distinguished in people in 1952 in Uganda and the United Republic of Tanzania. The explosions of the zika virus disease have been recorded in Africa, The Americas, Asia, and The Pacific. Gillian-Berre syndrome and congenital malformation (microcephaly) suspected to be linked with Zika virus. The virus can only be confirmed through laboratory test on blood or other body fluids, such as urine, saliva or semen. No specific antiviral treatment for Zika virus disease exists. Treatment is aimed at relieving symptoms with rest, fluid and medications. WHO/PAHO encourages the countries to establish and maintain Zika Virus infections, detection, clinical management and community assurances strategies to reduce transmission of the virus. The future of Zika Virus spreading to other parts of the world is still unknown.
Keywords: Zika Virus, flavivirus, Mosquito, Vaccine, Treatment, Microcephaly, WHO/PAHO.
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Shivaprasad, Shwetha, i Peter Sarnow. "Cross-species microRNA transmission modulates flavivirus growth in mosquitoes". Trends in Parasitology 38, nr 5 (maj 2022): 349–50. http://dx.doi.org/10.1016/j.pt.2022.02.007.
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Vanegas, Hernan, Fredman González, Yaoska Reyes, Edwing Centeno, Jayrintzina Palacios, Omar Zepeda, Marie Hagbom i in. "Zika RNA and Flavivirus-Like Antigens in the Sperm Cells of Symptomatic and Asymptomatic Subjects". Viruses 13, nr 2 (21.01.2021): 152. http://dx.doi.org/10.3390/v13020152.
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Zika virus (ZIKV) RNA has been found to remain in human semen for up to one year after infection, but the presence of Flavivirus antigens in the different compartments of semen has been largely unexplored. Following the introduction of ZIKV in Nicaragua (2016), a prospective study of patients with clinical symptoms consistent with ZIKV was conducted in León to investigate virus shedding in different fluids. ZIKV infection was confirmed in 16 male subjects (≥18 years of age) by RT-qPCR in either blood, saliva or urine. Of these, three provided semen samples at 7, 14, 21, 28, 60 and 180 days postsymptom onset (DPSO) for Flavivirus antigens and RNA studies. These cases were compared with 19 asymptomatic controls. Flavivirus antigens were examined by immunofluorescence (IF) using the 4G2 Mabs, and confocal microscopy was used to explore fluorescence patterns. The three (100%) symptomatic subjects and 3 (16%) of the 19 asymptomatic subjects had Flavivirus antigens and viral RNA in the spermatozoa fraction. The percentage of IF Flavivirus-positive spermatozoa cells ranged from 1.9% to 25% in specimens from symptomatic subjects, as compared with 0.8% to 3.8% in specimens from asymptomatic controls. A marked IF-pattern in the cytoplasmic droplets and tail of the spermatozoa was observed. The sperm concentrations (45 × 106/mL vs. 63.5 × 106/mL, p = 0.041) and the total motility percentage (54% vs. 75%, p = 0.009) were significantly lower in specimens from ZIKV-positive than in those of ZIKV-negative. In conclusion, this study demonstrated the presence of Flavivirus antigens and RNA within a time frame of 28 DPSO in sperm cells of symptomatic and asymptomatic subjects during the ZIKV epidemic. These findings have implications for public health, in terms of nonarthropod-born, silent transmission facilitated by sperm cells and potential transmission from asymptomatic males to pregnant women, with consequences to the fetus.
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Ogola, Edwin O., Armanda D. S. Bastos, Gilbert Rotich, Anne Kopp, Inga Slothouwer, Dorcus C. A. Omoga, Rosemary Sang, Baldwyn Torto, Sandra Junglen i David P. Tchouassi. "Analyses of Mosquito Species Composition, Blood-Feeding Habits and Infection with Insect-Specific Flaviviruses in Two Arid, Pastoralist-Dominated Counties in Kenya". Pathogens 12, nr 7 (24.07.2023): 967. http://dx.doi.org/10.3390/pathogens12070967.
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Insect-specific flaviviruses (ISFs), although not known to be pathogenic to humans and animals, can modulate the transmission of arboviruses by mosquitoes. In this study, we screened 6665 host-seeking, gravid and blood-fed mosquitoes for infection with flaviviruses and assessed the vertebrate hosts of the blood-fed mosquitoes sampled in Baringo and Kajiado counties; both dryland ecosystem counties in the Kenyan Rift Valley. Sequence fragments of two ISFs were detected. Cuacua virus (CuCuV) was found in three blood-fed Mansonia (Ma.) africana. The genome was sequenced by next-generation sequencing (NGS), confirming 95.8% nucleotide sequence identity to CuCuV detected in Mansonia sp. in Mozambique. Sequence fragments of a potential novel ISF showing nucleotide identity of 72% to Aedes flavivirus virus were detected in individual blood-fed Aedes aegypti, Anopheles gambiae s.l., Ma. africana and Culex (Cx.) univittatus, all having fed on human blood. Blood-meal analysis revealed that the collected mosquitoes fed on diverse hosts, primarily humans and livestock, with a minor representation of wild mammals, amphibians and birds. The potential impact of the detected ISFs on arbovirus transmission requires further research.
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Roldán, Julieta S., Alejandro Cassola i Daniela S. Castillo. "Development of a novel NS1 competitive enzyme-linked immunosorbent assay for the early detection of Zika virus infection". PLOS ONE 16, nr 8 (17.08.2021): e0256220. http://dx.doi.org/10.1371/journal.pone.0256220.
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Zika virus (ZIKV) is a flavivirus that has emerged as a global health threat after the 2015 outbreak in the Americas, where devastating congenital defects were documented. There are currently no vaccines to prevent ZIKV infections nor commercially available clinical diagnostic tests demonstrated to identify ZIKV without cross-reactive interference of related flaviviruses. Early diagnosis is critical when treating symptomatic patients and in preventing ZIKV transmission. In this context, the development of sensitive and accurate diagnostic methods are urgently needed for the detection of ZIKV acute infection. The aim of this study consisted of obtaining monoclonal antibodies (mAbs) against denatured monomeric ZIKV Nonstructural protein 1 (ZNS1), a useful diagnostic marker for flavivirus early detection, in order to develop a highly specific and sensitive ZNS1 indirect competitive ELISA (icELISA). The production of hybridomas secreting ZNS1 mAbs was carried out through immunizations with denatured monomeric ZNS1. We selected 1F5 and 6E2 hybridoma clones, which recognized the heat-denatured ZNS1 hexameric form by indirect ELISA. Cross-reaction studies indicated that these mAbs specifically bind to a ZNS1 linear epitope, and that they do not cross-react with the NS1 protein from other related flaviviruses. The 1F5 mAb enabled the development of a sensitive and reproducible icELISA to detect and quantify small amounts of ZNS1 disease marker in heat-denatured human sera. Here, we establish a reliable 1F5 based-icELISA that constitutes a promising diagnostic tool for control strategies and the prevention of ZIKV propagation.
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Samuel, Glady Hazitha, Michael R. Wiley, Atif Badawi, Zach N. Adelman i Kevin M. Myles. "Yellow fever virus capsid protein is a potent suppressor of RNA silencing that binds double-stranded RNA". Proceedings of the National Academy of Sciences 113, nr 48 (14.11.2016): 13863–68. http://dx.doi.org/10.1073/pnas.1600544113.
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Mosquito-borne flaviviruses, including yellow fever virus (YFV), Zika virus (ZIKV), and West Nile virus (WNV), profoundly affect human health. The successful transmission of these viruses to a human host depends on the pathogen’s ability to overcome a potentially sterilizing immune response in the vector mosquito. Similar to other invertebrate animals and plants, the mosquito’s RNA silencing pathway comprises its primary antiviral defense. Although a diverse range of plant and insect viruses has been found to encode suppressors of RNA silencing, the mechanisms by which flaviviruses antagonize antiviral small RNA pathways in disease vectors are unknown. Here we describe a viral suppressor of RNA silencing (VSR) encoded by the prototype flavivirus, YFV. We show that the YFV capsid (YFC) protein inhibits RNA silencing in the mosquitoAedes aegyptiby interfering with Dicer. This VSR activity appears to be broadly conserved in the C proteins of other medically important flaviviruses, including that of ZIKV. These results suggest that a molecular “arms race” between vector and pathogen underlies the continued existence of flaviviruses in nature.
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Grubaugh, Nathan D., Claudia Rückert, Philip M. Armstrong, Angela Bransfield, John F. Anderson, Gregory D. Ebel i Doug E. Brackney. "Transmission bottlenecks and RNAi collectively influence tick-borne flavivirus evolution". Virus Evolution 2, nr 2 (lipiec 2016): vew033. http://dx.doi.org/10.1093/ve/vew033.
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Masmejan, Sophie, Didier Musso, Manon Vouga, Leo Pomar, Pradip Dashraath, Milos Stojanov, Alice Panchaud i David Baud. "Zika Virus". Pathogens 9, nr 11 (28.10.2020): 898. http://dx.doi.org/10.3390/pathogens9110898.
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Zika virus (ZIKV), a neurotropic single-stranded RNA flavivirus, remains an important cause of congenital infection, fetal microcephaly, and Guillain-Barré syndrome in populations where ZIKV has adapted to a nexus involving the Aedes mosquitoes and humans. To date, outbreaks of ZIKV have occurred in Africa, Southeast Asia, the Pacific islands, the Americas, and the Caribbean. Emerging evidence, however, suggests that the virus also has the potential to cause infections in Europe, where autochtonous transmission of the virus has been identified. This review focuses on evolving ZIKV epidemiology, modes of transmission and host-virus interactions. The clinical manifestations, diagnostic issues relating to cross-reactivity to the dengue flavivirus and concerns surrounding ZIKV infection in pregnancy are discussed. In the last section, current challenges in treatment and prevention are outlined.
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Tan, Terence T. T., Raghavan Bhuvanakantham, Jun Li, Josephine Howe i Mah-Lee Ng. "Tyrosine 78 of premembrane protein is essential for assembly of West Nile virus". Journal of General Virology 90, nr 5 (1.05.2009): 1081–92. http://dx.doi.org/10.1099/vir.0.007872-0.
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Flavivirus premembrane (prM) protein plays an important role in conformational folding of the envelope (E) protein and protects it against premature fusion in acidic vesicles of the Golgi network. Currently, molecular determinants on the prM protein ectodomain which mediate critical steps during the flavivirus assembly process are poorly characterized. In this study, bioinformatics analysis and alanine scanning mutagenesis showed that the amino acid triplet valine 76, tyrosine 78 and glycine 79 is absolutely conserved among flavivirus prM ectodomains. Triple mutations engineered at these residues in prM ectodomain of West Nile virus (WNV) completely abrogated virus infectivity. Site-directed mutagenesis of prM protein revealed that tyrosine 78 of the amino acid triplet was required for virus infectivity and secretion. The mutation did not affect folding, post-translational modifications and trafficking of the prM and E proteins. Ultrastructural studies using transmission electron microscopy confirmed that virus particle formation was blocked by tyrosine 78 mutation. Specificity of assembly defect conferred by tyrosine 78 mutation was demonstrated by positive and negative trans complementation studies. Collectively, these results defined tyrosine 78 as a novel critical determinant present on prM protein ectodomain that is required for flavivirus assembly. Molecular dissection of prM protein function provides the crucial knowledge much needed in the elucidation of flavivirus particle formation.
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Bekal, Sadia, Leslie L. Domier, Biruk Gonfa, Nancy K. McCoppin, Kris N. Lambert i Kaustubh Bhalerao. "A novel flavivirus in the soybean cyst nematode". Journal of General Virology 95, nr 6 (1.06.2014): 1272–80. http://dx.doi.org/10.1099/vir.0.060889-0.
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Heterodera glycines, the soybean cyst nematode (SCN), is a subterranean root pathogen that causes the most damaging disease of soybean in the USA. A novel nematode virus genome, soybean cyst nematode virus 5 (SbCNV-5), was identified in RNA sequencing data from SCN eggs and second-stage juveniles. The SbCNV-5 RNA-dependent RNA polymerase and RNA helicase domains had homology to pestiviruses in the family Flaviviridae, suggesting that SbCNV-5 is a positive-polarity ssRNA virus. SbCNV-5 RNA was present in all nematode developmental stages, indicating a transovarial mode of transmission, but is also potentially sexually transmitted via the male. SbCNV-5 was common in SCN laboratory cultures and in nematode populations isolated from the field. Transmission electron microscopy of sections from a female SCN showed virus particles budding from the endoplasmic reticulum and in endosomes. The size of the viral genome was 19 191 nt, which makes it much larger than other known pestiviruses. Additionally, the presence of a methyltransferase in the SbCNV-5 genome is atypical for a pestivirus. When cDNA sequences were mapped to the genome of SbCNV-5, a disproportionate number aligned to the 3′ NTR, suggesting that SbCNV-5 produces a subgenomic RNA, which was confirmed by RNA blot analysis. As subgenomic RNAs and methyltransferases do not occur in pestiviruses, we conclude that SbCNV-5 is a new flavivirus infecting SCNs.
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Koh, Cassandra, Annabelle Henrion-Lacritick, Lionel Frangeul i Maria-Carla Saleh. "Interactions of the Insect-Specific Palm Creek Virus with Zika and Chikungunya Viruses in Aedes Mosquitoes". Microorganisms 9, nr 8 (3.08.2021): 1652. http://dx.doi.org/10.3390/microorganisms9081652.
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Palm Creek virus (PCV) is an insect-specific flavivirus that can interfere with the replication of mosquito-borne flaviviruses in Culex mosquitoes, thereby potentially reducing disease transmission. We examined whether PCV could interfere with arbovirus replication in Aedes (Ae.) aegypti and Ae. albopictus mosquitoes, major vectors for many prominent mosquito-borne viral diseases. We infected laboratory colonies of Ae. aegypti and Ae. albopictus with PCV to evaluate infection dynamics. PCV infection was found to persist to at least 21 days post-infection and could be detected in the midguts and ovaries. We then assayed for PCV–arbovirus interference by orally challenging PCV-infected mosquitoes with Zika and chikungunya viruses. For both arboviruses, PCV infection had no effect on infection and transmission rates, indicating limited potential as a method of intervention for Aedes-transmitted arboviruses. We also explored the hypothesis that PCV–arbovirus interference is mediated by the small interfering RNA pathway in silico. Our findings indicate that RNA interference is unlikely to underlie the mechanism of arbovirus inhibition and emphasise the need for empirical examination of individual pairs of insect-specific viruses and arboviruses to fully understand their impact on arbovirus transmission.
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Saivish, Marielena Vogel, Vivaldo Gomes da Costa, Gabriela de Lima Menezes, Roosevelt Alves da Silva, Gislaine Celestino Dutra da Silva, Marcos Lázaro Moreli, Livia Sacchetto, Carolina Colombelli Pacca, Nikos Vasilakis i Maurício Lacerda Nogueira. "Rocio Virus: An Updated View on an Elusive Flavivirus". Viruses 13, nr 11 (16.11.2021): 2293. http://dx.doi.org/10.3390/v13112293.
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Rocio virus (ROCV) is a mosquito-borne flavivirus and human pathogen. The virus is indigenous to Brazil and was first detected in 1975 in the Sao Paulo State, and over a period of two years was responsible for several epidemics of meningoencephalitis in coastal communities leading to over 100 deaths. The vast majority of ROCV infections are believed to be subclinical and clinical manifestations can range from uncomplicated fever to fatal meningoencephalitis. Birds are the natural reservoir and amplification hosts and ROCV is maintained in nature in a mosquito-bird-mosquito transmission cycle, primarily involving Psorophora ferox mosquitoes. While ROCV has remained mostly undetected since 1976, in 2011 it re-emerged in Goiás State causing a limited outbreak. Control of ROCV outbreaks depends on sustainable vector control measures and public education. To date there is no specific treatment or licensed vaccine available. Here we provide an overview of the ecology, transmission cycles, epidemiology, pathogenesis, and treatment options, aiming to improve our ability to understand, predict, and ideally avert further ROCV emergence.
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Li, Xuesong, Ying Shi, Qinfang Liu, Ying Wang, Guoxin Li, Qiaoyang Teng, Yuee Zhang, Sidang Liu i Zejun Li. "Airborne Transmission of a Novel Tembusu Virus in Ducks". Journal of Clinical Microbiology 53, nr 8 (10.06.2015): 2734–36. http://dx.doi.org/10.1128/jcm.00770-15.
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The routes of transmission of a newly emerged Tembusu virus (TMUV, Flavivirus ) in ducks in China remain unclear. Our epidemiological data show that TMUV is spread in winter, when mosquitos are inactive, which suggests that nonvector transmission routes are involved in the spread of TMUV. Furthermore, in vivo studies indicate that TMUV can be transmitted efficiently among ducks by both direct contact and aerosol transmission. This finding has important implications for the control of infection with this novel TMUV in the field.
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Beales, Lucy P., Andreas Holzenburg i David J. Rowlands. "Viral Internal Ribosome Entry Site Structures Segregate into Two Distinct Morphologies". Journal of Virology 77, nr 11 (1.06.2003): 6574–79. http://dx.doi.org/10.1128/jvi.77.11.6574-6579.2003.
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ABSTRACT An increasing number of viruses have been shown to initiate protein synthesis by a cap-independent mechanism involving internal ribosome entry sites (IRESs). Predictions of the folding patterns of these RNA motifs have been based primarily on sequence and biochemical analyses. Biophysical confirmation of the models has been achieved only for the IRES of hepatitis C virus (HCV), which adopts an open structure consisting of two major stems. We have conducted an extensive comparison of flavivirus and picornavirus IRES elements by negative stain transmission electron microscopy. All of the flavivirus IRESs we examined (those of GB virus-B, GB virus-C, and classical swine fever virus) fold to give a structure similar to that of the HCV IRES, as does an IRES recently found on mRNA encoded by human herpesvirus 8. The larger picornavirus IRESs (those of foot-and-mouth disease virus, rhinovirus, encephalomyocarditis virus, and hepatitis A virus) are morphologically similar, comprising a backbone with two protruding stems, and distinct from the flavivirus IRESs.
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Collins, Matthew H., i Jesse J. Waggoner. "Detecting Vertical Zika Transmission: Emerging Diagnostic Approaches for an Emerged Flavivirus". ACS Infectious Diseases 5, nr 7 (5.04.2019): 1055–69. http://dx.doi.org/10.1021/acsinfecdis.9b00003.
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Plante, Jessica A., Kenneth S. Plante, Vsevolod L. Popov, Divya P. Shinde, Steven G. Widen, Michaela Buenemann, Mauricio L. Nogueira i Nikos Vasilakis. "Morphologic and Genetic Characterization of Ilheus Virus, a Potential Emergent Flavivirus in the Americas". Viruses 15, nr 1 (10.01.2023): 195. http://dx.doi.org/10.3390/v15010195.
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Ilheus virus (ILHV) is a mosquito-borne flavivirus circulating throughout Central and South America and the Caribbean. It has been detected in several mosquito genera including Aedes and Culex, and birds are thought to be its primary amplifying and reservoir host. Here, we describe the genomic and morphologic characterization of ten ILHV strains. Our analyses revealed a high conservation of both the 5′- and 3′-untranslated regions but considerable divergence within the open reading frame. We also showed that ILHV displays a typical flavivirus structural and genomic organization. Our work lays the foundation for subsequent ILHV studies to better understand its transmission cycles, pathogenicity, and emergence potential.
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Casades-Martí, Laia, Rocío Holgado-Martín, Pilar Aguilera-Sepúlveda, Francisco Llorente, Elisa Pérez-Ramírez, Miguel Ángel Jiménez-Clavero i Francisco Ruiz-Fons. "Risk Factors for Exposure of Wild Birds to West Nile Virus in a Gradient of Wildlife-Livestock Interaction". Pathogens 12, nr 1 (3.01.2023): 83. http://dx.doi.org/10.3390/pathogens12010083.
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West Nile virus (WNV) transmission rate is shaped by the interaction between virus reservoirs and vectors, which may be maximized in farm environments. Based on this hypothesis, we screened for WNV in wild birds in three scenarios with decreasing gradient of interaction with horses: (i) the farm (A1); (ii) the neighborhood (A2); and (iii) a wild area (A3). We captured wild birds and analyzed their sera for WNV antibodies by blocking ELISA and micro-virus neutralization test. Flavivirus infections were tested with generic and specific PCR protocols. We parameterized linear mixed models with predictors (bird abundance and diversity, vector abundance, vector host abundance, and weather quantities) to identify Flavivirus spp. and WNV exposure risk factors. We detected a low rate of Flavivirus infections by PCR (0.8%) and 6.9% of the birds were seropositive by ELISA. Exposure to Flavivirus spp. was higher in A1 (9%) than in A2 and A3 (5.6% and 5.8%, respectively). Bird diversity was the most relevant predictor of exposure risk and passerines dominated the on-farm bird community. Our results suggest that measures deterring the use of the farm by passerines should be implemented because the environmental favorability of continental Mediterranean environments for WNV is increasing and more outbreaks are expected.
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Kurucz, Nina, Jamie Lee McMahon, Allan Warchot, Glen Hewitson, Jean Barcelon, Frederick Moore, Jasmin Moran i in. "Nucleic Acid Preservation Card Surveillance Is Effective for Monitoring Arbovirus Transmission on Crocodile Farms and Provides a One Health Benefit to Northern Australia". Viruses 14, nr 6 (20.06.2022): 1342. http://dx.doi.org/10.3390/v14061342.
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The Kunjin strain of West Nile virus (WNVKUN) is a mosquito-transmitted flavivirus that can infect farmed saltwater crocodiles in Australia and cause skin lesions that devalue the hides of harvested animals. We implemented a surveillance system using honey-baited nucleic acid preservation cards to monitor WNVKUN and another endemic flavivirus pathogen, Murray Valley encephalitis virus (MVEV), on crocodile farms in northern Australia. The traps were set between February 2018 and July 2020 on three crocodile farms in Darwin (Northern Territory) and one in Cairns (North Queensland) at fortnightly intervals with reduced trapping during the winter months. WNVKUN RNA was detected on all three crocodile farms near Darwin, predominantly between March and May of each year. Two of the NT crocodile farms also yielded the detection of MVE viral RNA sporadically spread between April and November in 2018 and 2020. In contrast, no viral RNA was detected on crocodile farms in Cairns during the entire trapping period. The detection of WNVKUN and MVEV transmission by FTATM cards on farms in the Northern Territory generally correlated with the detection of their transmission to sentinel chicken flocks in nearby localities around Darwin as part of a separate public health surveillance program. While no isolates of WNVKUN or MVEV were obtained from mosquitoes collected on Darwin crocodile farms immediately following the FTATM card detections, we did isolate another flavivirus, Kokobera virus (KOKV), from Culex annulirostris mosquitoes. Our studies support the use of the FTATM card system as a sensitive and accurate method to monitor the transmission of WNVKUN and other arboviruses on crocodile farms to enable the timely implementation of mosquito control measures. Our detection of MVEV transmission and isolation of KOKV from mosquitoes also warrants further investigation of their potential role in causing diseases in crocodiles and highlights a “One Health” issue concerning arbovirus transmission to crocodile farm workers. In this context, the introduction of FTATM cards onto crocodile farms appears to provide an additional surveillance tool to detect arbovirus transmission in the Darwin region, allowing for a more timely intervention of vector control by relevant authorities.
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Chiuya, Tatenda, Daniel K. Masiga, Laura C. Falzon, Armanda D. S. Bastos, Eric M. Fèvre i Jandouwe Villinger. "A survey of mosquito-borne and insect-specific viruses in hospitals and livestock markets in western Kenya". PLOS ONE 16, nr 5 (28.05.2021): e0252369. http://dx.doi.org/10.1371/journal.pone.0252369.
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Aedes aegypti and Culex pipiens complex mosquitoes are prolific vectors of arboviruses that are a global threat to human and animal health. Increased globalization and ease of travel have facilitated the worldwide dissemination of these mosquitoes and the viruses they transmit. To assess disease risk, we determined the frequency of arboviruses in western Kenyan counties bordering an area of high arboviral activity. In addition to pathogenic viruses, insect-specific flaviviruses (ISFs), some of which are thought to impair the transmission of specific pathogenic arboviruses, were also evaluated. We trapped mosquitoes in the short and long rainy seasons in 2018 and 2019 at livestock markets and hospitals. Mosquitoes were screened for dengue, chikungunya and other human pathogenic arboviruses, ISFs, and their blood-meal sources as determined by high-resolution melting analysis of (RT-)PCR products. Of 6,848 mosquitoes collected, 89% were trapped during the long rainy season, with A. aegypti (59%) and Cx. pipiens sensu lato (40%) being the most abundant. Most blood-fed mosquitoes were Cx. pipiens s.l. with blood-meals from humans, chicken, and sparrow (Passer sp.). We did not detect dengue or chikungunya viruses. However, one Culex poicilipes female was positive for Sindbis virus, 30 pools of Ae. aegypti had cell fusing agent virus (CFAV; infection rate (IR) = 1.27%, 95% CI = 0.87%-1.78%); 11 pools of Ae. aegypti had Aedes flavivirus (AeFV; IR = 0.43%, 95% CI = 0.23%-0.74%); and seven pools of Cx. pipiens s.l. (IR = 0.23%, 95% CI = 0.1%-0.45%) and one pool of Culex annulioris had Culex flavivirus. Sindbis virus, which causes febrile illness in humans, can complicate the diagnosis and prognosis of patients with fever. The presence of Sindbis virus in a single mosquito from a population of mosquitoes with ISFs calls for further investigation into the role ISFs may play in blocking transmission of other arboviruses in this region.
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Gothe, Leonard M. R., Stefanie Ganzenberg, Ute Ziegler, Anna Obiegala, Katharina L. Lohmann, Michael Sieg, Thomas W. Vahlenkamp, Martin H. Groschup, Uwe Hörügel i Martin Pfeffer. "Horses as Sentinels for the Circulation of Flaviviruses in Eastern–Central Germany". Viruses 15, nr 5 (30.04.2023): 1108. http://dx.doi.org/10.3390/v15051108.
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Since 2018, autochthonous West Nile virus (WNV) infections have been regularly reported in eastern–central Germany. While clinically apparent infections in humans and horses are not frequent, seroprevalence studies in horses may allow the tracing of WNV and related flaviviruses transmission, such as tick-borne encephalitis virus (TBEV) and Usutu virus (USUV), and consequently help to estimate the risk of human infections. Hence, the aim of our study was to follow the seropositive ratio against these three viruses in horses in Saxony, Saxony Anhalt, and Brandenburg and to describe their geographic distribution for the year 2021. In early 2022, i.e., before the virus transmission season, sera from 1232 unvaccinated horses were tested using a competitive pan-flavivirus ELISA (cELISA). In order to estimate the true seropositive ratio of infection with WNV, TBEV, and USUV for 2021, positive and equivocal results were confirmed by a virus neutralization test (VNT). In addition, possible risk factors for seropositivity using questionnaires were analyzed using logistic regression based on questionnaires similar to our previous study from 2020. In total, 125 horse sera reacted positive in the cELISA. Based on the VNT, 40 sera showed neutralizing antibodies against WNV, 69 against TBEV, and 5 against USUV. Three sera showed antibodies against more than one virus, and eight were negative based on the VNT. The overall seropositive ratio was 3.3% (95% CI: 2.38–4.40) for WNV, 5.6% (95% CI: 4.44–7.04) for TBEV, and 0.4% (95% CI: 0.14–0.98) for USUV infections. While age and number of horses on the holding were factors predicting TBEV seropositivity, no risk factors were discovered for WNV seropositivity. We conclude that horses are useful sentinels to determine the flavivirus circulation in eastern–central Germany, as long as they are not vaccinated against WNV.
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Platt, Derek J., Amber M. Smith, Nitin Arora, Michael S. Diamond, Carolyn B. Coyne i Jonathan J. Miner. "Zika virus–related neurotropic flaviviruses infect human placental explants and cause fetal demise in mice". Science Translational Medicine 10, nr 426 (31.01.2018): eaao7090. http://dx.doi.org/10.1126/scitranslmed.aao7090.
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Although Zika virus (ZIKV) infection in pregnant women can cause placental damage, intrauterine growth restriction, microcephaly, and fetal demise, these disease manifestations only became apparent in the context of a large epidemic in the Americas. We hypothesized that ZIKV is not unique among arboviruses in its ability to cause congenital infection. To evaluate this, we tested the capacity of four emerging arboviruses [West Nile virus (WNV), Powassan virus (POWV), chikungunya virus (CHIKV), and Mayaro virus (MAYV)] from related (flavivirus) and unrelated (alphavirus) genera to infect the placenta and fetus in immunocompetent, wild-type mice. Although all four viruses caused placental infection, only infection with the neurotropic flaviviruses (WNV and POWV) resulted in fetal demise. WNV and POWV also replicated efficiently in second-trimester human maternal (decidua) and fetal (chorionic villi and fetal membrane) explants, whereas CHIKV and MAYV replicated less efficiently. In mice, RNA in situ hybridization and histopathological analysis revealed that WNV infected the placenta and fetal central nervous system, causing injury to the developing brain. In comparison, CHIKV and MAYV did not cause substantive placental or fetal damage despite evidence of vertical transmission. On the basis of the susceptibility of human maternal and fetal tissue explants and pathogenesis experiments in immunocompetent mice, other emerging neurotropic flaviviruses may share with ZIKV the capacity for transplacental transmission, as well as subsequent infection and injury to the developing fetus.
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Tuplin, A., D. J. Evans, A. Buckley, I. M. Jones, E. A. Gould i T. S. Gritsun. "Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus". Nucleic Acids Research 39, nr 16 (27.05.2011): 7034–48. http://dx.doi.org/10.1093/nar/gkr237.
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Abstract We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem–loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents.
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Saiyasombat, Rungrat, Bethany G. Bolling, Aaron C. Brault, Lyric C. Bartholomay i Bradley J. Blitvich. "Evidence of Efficient Transovarial Transmission of Culex Flavivirus byCulex pipiens(Diptera: Culicidae)". Journal of Medical Entomology 48, nr 5 (1.09.2011): 1031–38. http://dx.doi.org/10.1603/me11043.
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Mac, Peter Asaga, Axel Kroeger, Theo Daehne, Chukwuma Anyaike, Raman Velayudhan i Marcus Panning. "Zika, Flavivirus and Malaria Antibody Cocirculation in Nigeria". Tropical Medicine and Infectious Disease 8, nr 3 (14.03.2023): 171. http://dx.doi.org/10.3390/tropicalmed8030171.
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Introduction. Arboviruses and malaria pose a growing threat to public health, affecting not only the general population but also immunocompromised individuals and pregnant women. Individuals in vulnerable groups are at a higher risk of severe complications from the co-circulation and transmission of ZIKV, malaria, and FLAVI fever. In sub-Saharan countries, such as Nigeria, these mosquito-borne infections have clinical presentations that overlap with other diseases (dengue, West Nile virus, and Japanese encephalitis, chikungunya, and O’nyong o’nyong virus), making them a diagnostic challenge for clinicians in regions where they co-circulate. Vertical transmission can have a devastating impact on maternal health and fetal outcomes, including an increased risk of fetal loss and premature birth. Despite the global recognition of the burden of malaria and arboviruses, particularly ZIKV and other flaviviruses, there is limited data on their prevalence in Nigeria. In urban settings, where these diseases are endemic and share common biological, ecological, and economic factors, they may impact treatment outcomes and lead to epidemiological synergy. Hence, it is imperative to conduct sero-epidemiological and clinical studies to better understand the disease burden and hidden endemicity, thereby enabling improved prevention and clinical management. Method. Serum samples collected from outpatients between December 2020 and November 2021 in three regions of Nigeria were tested for the presence of IgG antibody seropositivity against ZIKV and FLAVI using immunoblot serological assay. Results. The overall cohort co-circulation antibody seropositivity of ZIKV, FLAVI and malaria was 24.0% (209/871). A total of 19.2% (167/871) of the study participants had ZIKV-seropositive antibodies and 6.2% (54/871) were FLAVI-seropositive, while 40.0% (348/871) of the subjects had malaria parasite antigens. Regional analysis revealed that participants from the southern region had the highest antibody seropositivity against ZIKV (21.7% (33/152)) and FLAVI (8.6% (13/152)), whereas those from the central region had a higher malaria parasite antigen (68.5% (287/419)). Conclusions. This study represents the largest comparative cross-sectional descriptive sero-epidemiological investigation of ZIKV-FLAVI and malaria cocirculation in Nigeria. The findings of this study revealed increased antibody seropositivity, hidden endemicity, and the burden of ZIKV, FLAVI, and malaria co-circulating in Nigeria.
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Martin, Hélène, Jonathan Barthelemy, Yamileth Chin, Mathilde Bergamelli, Nathalie Moinard, Géraldine Cartron, Yann Tanguy Le Gac, Cécile E. Malnou i Yannick Simonin. "Usutu Virus Infects Human Placental Explants and Induces Congenital Defects in Mice". Viruses 14, nr 8 (25.07.2022): 1619. http://dx.doi.org/10.3390/v14081619.
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Usutu virus (USUV) is a neurotropic mosquito-borne flavivirus that has dispersed quickly in Europe these past years. This arbovirus mainly follows an enzootic cycle involving mosquitoes and birds, but can also infect other mammals, causing notably sporadic cases in humans. Although it is mainly asymptomatic or responsible for mild clinical symptoms, USUV has been associated with neurological disorders, such as encephalitis and meningoencephalitis, highlighting the potential health threat of this virus. Among the different transmission routes described for other flaviviruses, the capacity for some of them to be transmitted vertically has been demonstrated, notably for Zika virus or West Nile virus, which are closely related to USUV. To evaluate the ability of USUV to replicate in the placenta and gain access to the fetus, we combined the use of several trophoblast model cell lines, ex vivo human placental explant cultures from first and third trimester of pregnancy, and in vivo USUV-infected pregnant mice. Our data demonstrate that human placental cells and tissues are permissive to USUV replication, and suggest that viral transmission can occur in mice during gestation. Hence, our observations suggest that USUV could be efficiently transmitted by the vertical route.