Auswahl der wissenschaftlichen Literatur zum Thema „West African ZIKV“

Zika virus (ZIKV) has become a global health problem over the past decade due to the extension of the geographic distribution of the Asian/American genotype. Recent epidemics of Asian/American ZIKV have been associated with developmental disorders in humans. There is mounting evidence that African ZIKV may be associated with increased fetal pathogenicity necessitating to pay a greater attention towards currently circulating viral strains in sub-Saharan Africa. Here, we generated an infectious molecular clone GUINEA-18 of a recently transmitted human ZIKV isolate from West Africa, ZIKV-15555. The available infectious molecular clone MR766MC of historical African ZIKV strain MR766-NIID was used for a molecular clone-based comparative study. Viral clones GUINEA-18 and MR766MC were compared for their ability to replicate in VeroE6, A549 and HCM3 cell lines. There was a lower replication rate for GUINEA-18 associated with weaker cytotoxicity and reduced innate immune system activation compared with MR766MC. Analysis of chimeric viruses between viral clones stressed the importance of NS1 to NS4B proteins, with a particular focus of NS4B on GUINEA-18 replicative properties. ZIKV has developed strategies to prevent cytoplasmic stress granule formation which occurs in response to virus infection. GUINEA-18 was greatly efficient in inhibiting stress granule assembly in A549 cells subjected to a physiological stressor, with NS1 to NS4B proteins also being critical in this process. The impact of these GUINEA-18 proteins on viral replicative abilities and host-cell responses to viral infection raises the question of the role of nonstructural proteins in the pathogenicity of currently circulating ZIKV in sub-Saharan Africa.

Mosquito-borne Zika virus (ZIKV) from sub-Saharan Africa has recently gained attention due to its epidemic potential and its capacity to be highly teratogenic. To improve our knowledge on currently circulating strains of African ZIKV, we conducted protein sequence alignment and identified contemporary West Africa NS1 (NS1CWA) protein as a highly conserved viral protein. Comparison of NS1CWA with the NS1 of the historical African ZIKV strain MR766 (NS1MR766), revealed seven amino acid substitutions. The effects of NS1 mutations on protein expression, virus replication, and innate immune activation were assessed in human cells using recombinant NS1 proteins and a chimeric viral clone MR766 with NS1CWA replacing NS1MR766. Our data indicated higher secretion efficiency of NS1CWA compared to NS1MR766 associated with a change in subcellular distribution. A chimeric MR766 virus with NS1CWA instead of authentic protein displayed a greater viral replication efficiency, leading to more pronounced cell death compared to parental virus. Enhanced viral growth was associated with reduced activation of innate immunity. Our data raise questions of the importance of NS1 protein in the pathogenicity of contemporary ZIKV from sub-Saharan Africa and point to differences within viral strains of African lineage.

Zika virus (ZIKV) infections have been recognised in Africa and Asia since 1940. The virus is in the family Flaviviridae and genus Flavivirus, along with Dengue, Japanese encephalitis virus, Tick borne encephalitis, West Nile virus, and Yellow fever virus. These viruses share biological characteristics of an envelope, icosahedral nucleocapsid, and a non-segmented, positive sense, single-strand RNA genome of ~10kb encoding three structural proteins (capsid C pre-membrane/membrane PrM/M, envelope E), and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). ZIKV has three known genotypes; the West African (Nigerian cluster), East African (MR766 prototype cluster), and Asian strains. Virus sequencing from the most recent South American outbreak suggests this virus is related to the 2013 French Polynesian isolates of Asian lineage.

The explosive emergence of Zika virus (ZIKV) across the Pacific and Americas since 2007 was associated with hundreds of thousands of human cases and severe outcomes, including congenital microcephaly caused by ZIKV infection during pregnancy. Although ZIKV was first isolated in Uganda, Africa has so far been exempt from large-scale ZIKV epidemics, despite widespread susceptibility among African human populations. A possible explanation for this pattern is natural variation among populations of the primary vector of ZIKV, the mosquito Aedes aegypti. Globally invasive populations of Ae. aegypti outside of Africa are considered effective ZIKV vectors because they are human specialists with high intrinsic ZIKV susceptibility, whereas African populations of Ae. aegypti across the species’ native range are predominantly generalists with low intrinsic ZIKV susceptibility, making them less likely to spread viruses in the human population. We test this idea by studying a notable exception to the patterns observed across most of Africa: Cape Verde experienced a large ZIKV outbreak in 2015 to 2016. We find that local Ae. aegypti in Cape Verde have substantial human-specialist ancestry, show a robust behavioral preference for human hosts, and exhibit increased susceptibility to ZIKV infection, consistent with a key role for variation among mosquito populations in ZIKV epidemiology. These findings suggest that similar human-specialist populations of Ae. aegypti in the nearby Sahel region of West Africa, which may be expanding in response to rapid urbanization, could serve as effective vectors for ZIKV in the future.

The Zika virus (ZIKV) belongs to the genus Flavivirus, together with Dengue virus, yellow fever virus, and West Nile virus. The virus, which was first found in Africa in 1947, has spread across the world owing to a lack of effective drugs or vaccines. The complete genome sequence of ZIKV is now available; it includes three structural and seven non-structure genes arranged in the order of capsid, pre-membrane, envelope, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. Two geographically distinct lineages are known, i.e., Asian and African, but ZIKV exhibits differences in clinical progression among regions.

The link between Zika virus infection during pregnancy and microcephaly and other neurodevelopmental defects in infants, referred to as congenital Zika syndrome (CZS), was recently discovered. One key question that remains is whether such neurodevelopmental abnormalities are limited to the recently evolved Asiatic ZIKV strains or if they can also be induced by endemic African strains. Thus, we examined birth registries from one particular hospital from a country in West Africa, where ZIKV is endemic. Results showed a seasonal pattern of birth defects that is consistent with potential CZS, which correspond to a range of presumed maternal infection that encompasses both the peak of the warm, rainy season as well as the months immediately following it, when mosquito activity is likely high. While we refrain from definitively linking ZIKV infection and birth defects in West Africa at this time, in part due to scant data available from the region, we hope that this report will initiate broader surveillance efforts that may help shed light onto mechanisms underlying CZS.

The link between Zika virus infection during pregnancy and microcephaly and other neurodevelopmental defects in infants, referred to as congenital Zika syndrome (CZS), was recently discovered. One key question that remains is whether such neurodevelopmental abnormalities are limited to the recently evolved Asiatic ZIKV strains or if they can also be induced by endemic African strains. Thus, we examined birth registries from one particular hospital from a country in West Africa, where ZIKV is endemic. Results showed a seasonal pattern of birth defects that is consistent with potential CZS, which corresponds to a range of presumed maternal infection that encompasses both the peak of the warm, rainy season as well as the months immediately following it, when mosquito activity is likely high. While we refrain from definitively linking ZIKV infection and birth defects in West Africa at this time, in part due to scant data available from the region, we hope that this report will initiate broader surveillance efforts that may help shed light onto mechanisms underlying CZS.

The Zika virus (ZIKV) is a widespread mosquito-borne pathogen. Phylogenetically, two lineages of ZIKV are distinguished: African and Asian–American. The latter became the cause of the 2015–2016 pandemic, with severe consequences for newborns. In West African countries, the African lineage was found, but there is evidence of the emergence of the Asian–American lineage in Cape Verde and Angola. This highlights the need to not only monitor ZIKV but also sequence the isolates. In this article, we present a case report of Zika fever in a pregnant woman from Guinea identified in 2018. Viral RNA was detected through qRT-PCR in a serum sample. In addition, the seroconversion of anti-Zika IgM and IgG antibodies was detected in repeated blood samples. Subsequently, the virus was isolated from the C6/36 cell line. The detected ZIKV belonged to the African lineage, the Nigerian sublineage. The strains with the closest sequences were isolated from mosquitoes in Senegal in 2011 and 2015. In addition, we conducted the serological screening of 116 blood samples collected from patients presenting to the hospital of Faranah with fevers during the period 2018–2021. As a result, it was found that IgM-positive patients were identified each year and that the seroprevalence varied between 5.6% and 17.1%.

African populations of the mosquito Aedes aegypti are usually considered less susceptible to infection by human-pathogenic flaviviruses than globally invasive populations found outside Africa. Although this contrast has been well documented for Zika virus (ZIKV), it is unclear to what extent it is true for dengue virus (DENV), the most prevalent flavivirus of humans. Addressing this question is complicated by substantial genetic diversity among DENV strains, most notably in the form of four genetic types (DENV1 to DENV4), that can lead to genetically specific interactions with mosquito populations. Here, we carried out a survey of DENV susceptibility using a panel of seven field-derived Ae. aegypti colonies from across the African range of the species and a colony from Guadeloupe, French West Indies as non-African reference. We found considerable variation in the ability of African Ae. aegypti populations to acquire and replicate a panel of six DENV strains spanning the four DENV types. Although African Ae. aegypti populations were generally less susceptible than the reference non-African population from Guadeloupe, in several instances some African populations were equally or more susceptible than the Guadeloupe population. Moreover, the relative level of susceptibility between African mosquito populations depended on the DENV strain, indicating genetically specific interactions. We conclude that unlike ZIKV susceptibility, there is no clear-cut dichotomy in DENV susceptibility between African and non-African Ae. aegypti. DENV susceptibility of African Ae. aegypti populations is highly heterogeneous and largely governed by the specific pairing of mosquito population and DENV strain.

Abstract Human immunoglobulin (IgM) antibody capture enzyme linked immunosorbent assay (MAC-ELISA) is recommended by US Centers for Disease Control (CDC) to detect the Zika Virus (ZIKV) infection in samples collected after few days of the onset of disease. However, the cross-reactivity of IgM and immunoglobulin G (IgG) antibodies to ZIKV with dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV) and some other related flaviviruses poses a significant challenge for an accurate detection of ZIKV infection in a singleplex serological assay. To overcome these challenges we developed a novel multiplex serological assay that will simultaneously detect antibody response to ZIKV, other related flaviviruses and Chikungunya virus (CHIKV). Various recombinant arboviral antigens were coupled to optically-coded microspheres from Luminex Corporation. This fluorescent labeled microsphere assay was used to differentiate between recent, past arbovirus infections, or co-infections that may occur in endemic regions. We used plasma samples from non-human primates (NHPs) prior to and after ZIKV infection for longitudinal assessment of IgM and IgG antibody responses for evaluation of this method. 37 blood samples from 5 different animals challenged with either African strain or Asian lineage strain of ZIKV were analyzed for antibody responses to multiple antigens included in this test. We developed a detection algorithm for automation of IgM result analysis to differentiate ZIKV IgM response from other arboviruses. Thus this multiplex arbovirus assay has great promise for testing human samples for detecting ZIKV infection.

Le virus Zika (ZIKV), historiquement limité à l'Afrique et à l'Asie, est devenu une préoccupation mondiale majeure, surtout après les épidémies récentes dans les Amériques associées à des malformations congénitales graves et des troubles neurologiques. Bien que la recherche se soit principalement concentrée sur le génotype asiatique/américain, des preuves croissantes montrent que les souches africaines du ZIKV pourraient également représenter une menace sévère, notamment en termes de pathogénicité fœtale. Cette thèse vise à améliorer notre compréhension des mécanismes moléculaires de la pathogénicité des souches contemporaines de ZIKV d'Afrique de l'Ouest, en mettant l'accent sur les protéines non structurales dans la réplication virale, l'évasion immunitaire et la réponse au stress des cellules hôtes.Pour cela, nous avons généré un clone moléculaire infectieux, GUINEA-18, à partir d'une souche de ZIKV (ZIKV-15555) isolée en Guinée en 2018, représentant une souche contemporaine de la lignée africaine. Nous avons comparé ce clone avec le clone bien caractérisé de la souche historique MR766 (MR766MC). Les propriétés de réplication des deux clones ont été examinées dans les lignées cellulaires VeroE6, A549 et HCM3. GUINEA-18 a montré un taux de réplication plus lent, une cytotoxicité réduite et une moindre capacité à activer le système immunitaire inné comparé à MR766MC, suggérant une interaction différente avec les cellules hôtes.Pour explorer ces différences, nous avons construit des virus chimériques en échangeant les régions codantes des protéines non structurales entre GUINEA-18 et MR766MC. Nos résultats ont souligné les rôles critiques des protéines NS1 à NS4B dans la réplication et la pathogénicité, avec NS4B étant clé pour GUINEA-18. Nous avons également découvert que GUINEA-18 inhibe efficacement l'assemblage des granules de stress cytoplasmiques (SGs) dans les cellules A549, un mécanisme de défense cellulaire. Cette inhibition dépend des protéines NS1 à NS4B, soulignant leur rôle dans l'évasion des défenses de l'hôte.La thèse examine aussi le rôle de NS1 dans la pathogénicité des souches contemporaines. L'alignement des séquences protéiques a révélé sept substitutions dans la protéine NS1 de GUINEA-18 par rapport à celle de MR766. Ces mutations montrent que NS1CWA est sécrétée plus efficacement et présente une localisation subcellulaire différente de NS1MR766, augmentant la réplication virale et la cytotoxicité tout en réduisant l'activation des réponses immunitaires. Un virus chimérique MR766 avec NS1CWA a montré ces traits pathogéniques renforcés, soulignant l'importance de NS1 dans la virulence des souches contemporaines du ZIKV d'Afrique de l'Ouest.En conclusion, cette thèse analyse les déterminants moléculaires de la réplication et de la pathogénicité des souches contemporaines du ZIKV d'Afrique de l'Ouest. Les recherches mettent en évidence les rôles critiques des protéines NS1 à NS4B, en particulier NS1 et NS4B. Les résultats soulèvent des questions sur les risques associés aux souches actuelles du ZIKV en Afrique subsaharienne et soulignent la nécessité de surveillance continue pour comprendre les implications pour la santé publique. Ce travail offre des perspectives pour les stratégies de gestion et de prévention des maladies associées au ZIKV, surtout dans les régions où la lignée africaine est prévalente
The Zika virus (ZIKV), historically confined to Africa and Asia, has become a significant global health concern, especially after recent outbreaks in the Americas linked to severe congenital malformations and neurological disorders. While much research has focused on the Asian/American ZIKV genotype, evidence suggests that African ZIKV strains might also pose a serious threat to public health, particularly regarding fetal pathogenicity. This thesis aims to enhance our understanding of the molecular mechanisms underlying the pathogenicity of contemporary ZIKV strains from West Africa, focusing on nonstructural proteins involved in viral replication, immune evasion, and the host cell stress response.To achieve this, we generated an infectious molecular clone, GUINEA-18, from a ZIKV strain (ZIKV-15555) isolated in Guinea in 2018. This clone represents a contemporary African ZIKV strain. We compared it with the infectious molecular clone of the historical African ZIKV strain MR766, designated MR766MC. The replication properties of both viral clones were examined in VeroE6, A549, and HCM3 cells. GUINEA-18 exhibited a slower replication rate, reduced cytotoxicity, and a lower ability to activate the host’s innate immune system compared to MR766MC, suggesting different interactions with host cells.To dissect these differences, we created chimeric viruses by swapping nonstructural protein-coding regions between GUINEA-18 and MR766MC. Results highlighted the critical roles of NS1 to NS4B proteins in replication efficiency and pathogenicity, with NS4B being crucial for GUINEA-18’s replication properties. GUINEA-18 also developed an efficient mechanism to inhibit the assembly of cytoplasmic stress granules (SGs) in A549 cells, a defense mechanism typically triggered by viral infection. The ability of GUINEA-18 to block SG formation depended on the NS1 to NS4B proteins, underscoring their role in evading host defenses.Further investigation into the NS1 protein revealed seven amino acid substitutions in GUINEA-18 compared to MR766. Functional analyses showed that the contemporary NS1 protein (NS1CWA) is secreted more efficiently and has a different subcellular localization than NS1 from MR766 (NS1MR766). This altered behavior of NS1CWA significantly enhances viral replication and cytotoxicity while reducing the activation of innate immune responses in infected cells. A chimeric MR766 virus containing NS1CWA demonstrated these enhanced traits, emphasizing NS1’s role in the virulence of contemporary West African ZIKV strains.In conclusion, this thesis provides a comprehensive analysis of the molecular determinants of replication and pathogenicity in contemporary West African ZIKV strains. The research underscores the crucial roles of NS1 to NS4B proteins, particularly NS1 and NS4B, in these processes. The findings raise questions about risks associated with circulating ZIKV strains in sub-Saharan Africa and highlight the need for ongoing surveillance and research to understand the public health implications. This work contributes valuable insights that could inform future strategies for managing and preventing ZIKV-associated diseases, especially in regions where the African lineage of the virus is prevalent

Zika virus is a flavivirus transmitted by mosquitoes of the Aedes genus, isolated for the first time in Uganda in 1947 and usually associated with a mild disease clinically similar to other arbovirosis, such as Dengue and Chikungunya fevers. Few cases of infection were reported until 2007, when an outbreak occurred in Micronesia, followed by a large epidemic in French Polynesia and the Americas. During its emergence, Zika virus has been associated with more severe clinical manifestations, including neurological sequelae and congenital defects such as microcephaly. Before the recent spread, serological investigations conducted between the 1960s and the 1990s showed the wide presence of Zika virus in Africa. However, limited data are available on the recent prevalence in the African population. According to the World Health Organization, the entire Africa continent is at risk of Zika outbreak due to the presence of the virus, competent vectors and the low capacity of surveillance and containment of an epidemic. In the context of West Africa, three countries with different transmission potential have been identified: Senegal, with present local cases; Mali, with only serological evidences; and The Gambia with local cases of Dengue and Chikungunya. The aim of this study was to evaluate the immunity against Zika virus in samples of a selected cohort for each of these countries, in order to investigate the circulation of the virus in the region during the first years of its emergence in the Pacific. Human serum samples were collected in 2007 and between 2011 and 2012 from a cohort of subjects residing in Mali, Senegal and The Gambia. Samples were tested using an ELISA detection kit and positives were further confirmed by microneutralization test. Results indicate that Zika virus is present and actively circulating in Senegal and The Gambia. Although no significant differences were found in prevalence during the time period considered, seroconversion of some subjects showed the active circulation of Zika virus in the West African area. Analysis by age showed an increase in immunity in relation with increasing age, demonstrating that the population is consistently exposed to the virus throughout life and with a high possibility to be infected during reproductive-age. In conclusion, the results obtained allow a better knowledge of the circulation of Zika virus within three different ecological and demographic contexts, updating the few data currently available.

Differential diagnosis of fevers?, Fever without localizing features?, Sepsis?, Cancer?, General rules of cancer management?, Rheumatoid arthritis?, Osteoarthritis?, Systemic lupus erythematosus?, Typhoid and paratyphoid fevers?, Rickettsioses?, Bartonella?, Ehrlichia?, Coxiella?, Relapsing fevers?, Leptospirosis?, Brucellosis?, Plague?, Melioidosis?, Anthrax?, African trypanosomiasis?, American trypanosomiasis?, Visceral leishmaniasis (kala-azar)?, Infectious mononucleosis?, Measles?, Arboviruses and zoonotic haemorrhagic fever viruses , Ebola and Marburg virus diseases, Crimean-Congo haemorrhagic fever, Rift Valley fever, Lassa fever, Hantavirus infections, Severe fever and thrombocytopenia, Zika virus, Japanese encephalitis , Dengue virus, Yellow fever, West Nile virus , Kyasanur Forest Disease, Chikungunya, Ross River fever, O'nyong nyong

This chapter analyses the empirical examples of each PHEIC which has been declared, to understand the application of the legal criteria and political considerations. Starting with H1N1, and considering polio; Ebola in West-Africa; Zika; Ebola in DRC; and COVID-19 – for each outbreak we consider the background to the epidemic, the PHEIC decision making offered by supporting documentation; the temporary recommendations suggested by WHO; and further additional reflections as to the PHEIC process and utilisation.

This chapter focuses on flaviviruses and notes that there are at least 70 serotypes of flavivirus. The molecular clock analysis dates the sojourn of these viruses from 10 to 100,000 years. The prototype virus of this family causes yellow fever (YF), which is a classic disease of antiquity, and the application of the term ‘white man’s grave’ to West Africa resulted from its impact on colonizers. The chapter refers to Carlos Finlay, who viewed the mosquito as the source and scourge of YF, but this was not proven until the volunteer experiments coordinated by Walter Reed in 1900. Other medically important flaviviruses are tick-borne encephalitis virus (TBE), dengue virus and West Nile virus, Japanese encephalitis, Murray Valley encephalitis virus, and Zika virus. The chapter highlights the hepatitis C virus, a well-researched member of the family that does not have the typical mosquito transmission of the other flaviviruses.

Following the recent global health crises, such as the 2014 Ebola and 2016 ZIKA outbreaks, the international health community’s ability to deal with such threats has been debated. Amid discussions of how international health security (IHS) and related national health systems should and could be strengthened, the potential of harnessing the role of civil society organizations (CSOs) for more effective responses has been frequently raised. Such participation is often based on the notion that CSOs by their grassroots presence can more effectively help to address health security and health systems challenges in affected populations and communities. Using the World Health Organization’s (WHO) health systems’ building blocks as an evaluative framework, this chapter examines CSOs’ roles and responsibilities during the 2014–2016 West Africa Ebola Outbreak and how they can be further empowered to perform these functions. The chapter draws conclusions about the opportunities and challenges CSOs represent for strengthening IHS and national health systems during public health emergencies in low- and middle-income countries (LMICs).

Following the recent global health crises, such as the 2014 Ebola and 2016 ZIKA outbreaks, the international health community’s ability to deal with such threats has been debated. Amid discussions of how international health security (IHS) and related national health systems should and could be strengthened, the potential of harnessing the role of civil society organizations (CSOs) for more effective responses has been frequently raised. Such participation is often based on the notion that CSOs by their grassroots presence can more effectively help to address health security and health systems challenges in affected populations and communities. Using the World Health Organization’s (WHO) health systems’ building blocks as an evaluative framework, this chapter examines CSOs’ roles and responsibilities during the 2014–2016 West Africa Ebola Outbreak and how they can be further empowered to perform these functions. The chapter draws conclusions about the opportunities and challenges CSOs represent for strengthening IHS and national health systems during public health emergencies in low- and middle-income countries (LMICs).