Journal articles: 'Human Astrovirus'

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Kapoor, A., L. Li, J. Victoria, B. Oderinde, C. Mason, P. Pandey, S. Z. Zaidi, and E. Delwart. "Multiple novel astrovirus species in human stool." Journal of General Virology 90, no. 12 (December 1, 2009): 2965–72. http://dx.doi.org/10.1099/vir.0.014449-0.

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Diarrhoea remains a significant cause of morbidity and mortality in developing countries where numerous cases remain without identified aetiology. Astroviruses are a recently identified cause of animal gastroenteritis which currently includes two species suspected of causing human diarrhoea. Using pan-astrovirus RT-PCR, we analysed human stool samples from different continents for astrovirus-related RNA sequences. We identified variants of the two known human astrovirus species plus, based on genetic distance criteria, three novel astrovirus species all distantly related to mink and ovine astroviruses, which we provisionally named HMOAstV species A–C. The complete genome of species A displayed all the conserved characteristics of mammalian astroviruses. Each of the now three groups of astroviruses found in human stool (HAstV, AstV-MLB and HMOAstV) were more closely related to animal astroviruses than to each other, indicating that human astroviruses may periodically emerge from zoonotic transmissions. Based on the pathogenic impact of their closest phylogenetic relatives in animals, further investigations of the role of HMOAstV, so far detected in Nigeria, Nepal and Pakistan, in human gastroenteritis are warranted.

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Giordano, Miguel O., Laura C. Martinez, María B. Isa, Mirtha Paez Rearte, and Silvia V. Nates. "Childhood astrovirus-associated diarrhea in the ambulatory setting in a Public Hospital in Cordoba city, Argentina." Revista do Instituto de Medicina Tropical de São Paulo 46, no. 2 (April 2004): 93–96. http://dx.doi.org/10.1590/s0036-46652004000200007.

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Human astroviruses have been increasingly identified as important agents of diarrheal disease in children. However, the disease burden of astrovirus infection is still incompletely assessed. This paper reports results on the epidemiological and clinical characteristics of astrovirus-associated diarrhea, as well as the impact of astrovirus infection on the ambulatory setting at a Public Hospital in Córdoba city, Argentina. From February 2001 through January 2002, 97 randomly selected outpatient visits for diarrhea among children < 36 months old were enrolled. A single specimen of stool from each child was collected and tested for astrovirus antigen by enzyme immunoassay. Astroviruses were detected in 12.37% of the diarrheal episodes. All the positive cases occurred in children 4 to 18 months, but the highest rate was in children aged 4 to 6 months (23.80%). The clinical symptoms of astrovirus associated-diarrhea were fever 41.66%, vomiting 25.00% and dehydration 8.33%; overall 16.66% required hospitalization. Astrovirus was identified through the year and no seasonally pattern was detected (cool semester 15.21% versus warm semester 9.80% p > 0.05). According to our estimation about one out of seventy-four children in this cohort would be assisted annually for an astroviral-diarrheal episode in the Public Hospital and one out of eight diarrheal cases could be attributed to astrovirus infection. Astrovirus is a common symptomatic infection in pediatric outpatient visits in the public hospital in the study area, contributing 12.37% of the overall morbidity from diarrhea.

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Jonassen, Christine M., Tom Ø. Jonassen, Yehia M. Saif, David R. Snodgrass, Hiroshi Ushijima, Mitsugu Shimizu, and Bjørn Grinde. "Comparison of capsid sequences from human and animal astroviruses." Journal of General Virology 82, no. 5 (May 1, 2001): 1061–67. http://dx.doi.org/10.1099/0022-1317-82-5-1061.

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We have sequenced the genomic 3′-end, including the structural gene, of human astrovirus (HAstV) serotype 7 and morphologically related viruses infecting pig (PAstV), sheep (OAstV) and turkey (TAstV-1). These sequences were compared with corresponding astrovirus sequences available in the nucleic acid databases, including sequences of the seven other HAstV serotypes, two other avian astroviruses (TAstV-2 and avian nephritis virus) and astrovirus from cat (FAstV). A 35 nt stem–loop motif near the 3′-end of the genome, previously described as being highly conserved, was present in all of the astroviruses except TAstV-2. In the N-terminal half of the capsid precursor protein, there were several short conserved peptide motifs. Otherwise the capsid proteins of astroviruses infecting different hosts were highly divergent. Calculation of genetic distances revealed that the distance between FAstV and HAstV is comparable to the largest distances between different HAstV serotypes. Higher similarities between the HAstV, FAstV and PAstV capsid sequences suggest interspecies transmissions involving humans, cats and pigs relatively recently in the evolutionary history of astroviruses.

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Moser, Lindsey A., Michael Carter, and Stacey Schultz-Cherry. "Astrovirus Increases Epithelial Barrier Permeability Independently of Viral Replication." Journal of Virology 81, no. 21 (August 15, 2007): 11937–45. http://dx.doi.org/10.1128/jvi.00942-07.

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ABSTRACT Astrovirus infection in a variety of species results in an age-dependent diarrhea; however, the means by which astroviruses cause diarrhea remain unknown. Studies of astrovirus-infected humans and turkeys have demonstrated few histological changes and little inflammation during infection, suggesting that intestinal damage or an overzealous immune response is not the primary mediator of astrovirus diarrhea. An alternative contributor to diarrhea is increased intestinal barrier permeability. Here, we demonstrate that astrovirus increases barrier permeability in a Caco-2 cell culture model system following apical infection. Increased permeability correlated with disruption of the tight-junction protein occludin and decreased the number of actin stress fibers in the absence of cell death. Additionally, permeability was increased when monolayers were treated with UV-inactivated virus or purified recombinant human astrovirus serotype 1 capsid in the form of virus-like particles. Together, these results demonstrate that astrovirus-induced permeability occurs independently of viral replication and is modulated by the capsid protein, a property apparently unique to astroviruses. Based on these data, we propose that the capsid contributes to diarrhea in vivo.

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Pankovics, Péter, Ákos Boros, Melinda Rovács, Erika Nagy, Erika Krisztián, Mária Vollain, and Gábor Reuter. "First detection of human astrovirus in gastroenteritis outbreak in Hungary." Orvosi Hetilap 152, no. 2 (January 2011): 45–50. http://dx.doi.org/10.1556/oh.2011.29013.

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Human astroviruses are one of the known pathogens of gastroenteritis in infants, children and rarely in elderly. It causes 4.2-7.3% of the sporadic gastroenteritis cases with diarrhea and vomiting in children. The etiological role of astrovirus has not been confirmed yet in outbreaks of gastroenteritis in Hungary. Aims: The first description of the detection and molecular epidemiology of astrovirus in outbreaks of gastroenteritis in Hungary. Materials and methods: Stool samples originated from Komárom-Esztergom County, from a day-care center (nursery) where a gastroenteritis outbreak occurred in June, 2010. Astrovirus was detected by RT-PCR methods. The nucleotide sequence of the nearly complete genome was sequenced. Clinical and epidemiological data were collected by epidemiological investigation. Results: Out of the 29 exposed persons (24 children and 5 adults) 7 (24.1%) children had gastroenteritis with diarrhea, and vomiting in one case, in the period of June 4-15, 2010. Bacterial pathogens, rotavirus, adenovirus and norovirus were not detected, but genotype 1 astrovirus could be identified in 3 (42.8%) stool samples (HQ398856). The nucleotide sequence of the astrovirus ORF1a/ORF1b/ORF2/3’UTR regions was determined. The source of the outbreak was presumably the firstly recognized ill child and the virus was spread by fecal-oral route with direct contact in the children community. Conclusions: Epidemiologic and clinical characteristics of the astrovirus outbreak in the nursery are described in details to prove that the possible etiological role of astroviruses in viral gastroenteritis which should not forget in order after rotaviruses, caliciviruses (norovirus and sapovirus) and enteric adenoviruses. Orv. Hetil., 2011, 152, 45–50.

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Roach, Shanley N., and Ryan A. Langlois. "Intra- and Cross-Species Transmission of Astroviruses." Viruses 13, no. 6 (June 11, 2021): 1127. http://dx.doi.org/10.3390/v13061127.

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Astroviruses are non-enveloped, single-stranded RNA viruses that infect mammalian and avian species. In humans, astrovirus infections are one of the most common causes of gastroenteritis in children. Infection has also been linked to serious neurological complications, especially in immunocompromised individuals. More extensive disease has also been characterized in non-human mammalian and avian species. To date, astroviruses have been detected in over 80 different avian and mammalian hosts. As the number of hosts continues to rise, the need to understand how astroviruses transmit within a given species as well as to new host species becomes increasingly important. Here, we review the current understanding of astrovirus transmission, the factors that influence viral spread, and the potential for cross-species transmission. Additionally, we highlight the current gaps in knowledge and areas of future research that will be key to understanding astrovirus transmission and zoonotic potential.

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Koopmans, M. P. G., M. H. L. Bijen, S. S. Monroe, and J. Vinjé. "Age-Stratified Seroprevalence of Neutralizing Antibodies to Astrovirus Types 1 to 7 in Humans in The Netherlands." Clinical Diagnostic Laboratory Immunology 5, no. 1 (January 1, 1998): 33–37. http://dx.doi.org/10.1128/cdli.5.1.33-37.1998.

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ABSTRACT Astroviruses are a new family of positive-stranded RNA viruses that cause gastroenteritis in a wide range of animals and in humans. Seven types of astrovirus, tentatively considered serotypes, have been distinguished by enzyme-linked immunosorbent assays (ELISA) or immunoelectron microscopy, but it is unclear whether the serotype designation is used properly. To test human sera for the presence of neutralizing antibodies and to type field strains, neutralization tests (NT) using CaCo2 tissue-culture-adapted astrovirus strains 1 to 7 and the corresponding rabbit reference sera were developed. In rabbits, neutralizing antibodies were predominantly serotype specific, with the exception of low-level cross-reactivity in astrovirus serotype 4 reference serum with astrovirus serotype 1 virus. Similarly, in humans, no evidence of cross-reactivity was found for the serotype combinations tested (all except the combination 1 and 7 and the combination 6 and 7). Typing by NT was concordant with typing by ELISA and genotyping, with one exception. The seroprevalence rates of neutralizing antibodies in an age-stratified sample of the population in Utrecht Province (n = 242) were 91% for astrovirus serotype 1, 69% for astrovirus serotype 3, 56% for astrovirus serotype 4, 36% for astrovirus serotype 5, 31% for astrovirus serotype 2, 16% for astrovirus serotype 6, and 10% for astrovirus serotype 7. Acquisition of antibodies was slower among persons seropositive for astrovirus serotype 5 than among those seropositive for astrovirus serotypes 1 to 4, suggesting that the epidemiology of serotype 5 astrovirus is different from that of astrovirus serotypes 1 to 4.

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York, Royce L., Payam A. Yousefi, Walter Bogdanoff, Sara Haile, Sarvind Tripathi, and Rebecca M. DuBois. "Structural, Mechanistic, and Antigenic Characterization of the Human Astrovirus Capsid." Journal of Virology 90, no. 5 (December 9, 2015): 2254–63. http://dx.doi.org/10.1128/jvi.02666-15.

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ABSTRACTHuman astroviruses (HAstVs) are nonenveloped, positive-sense, single-stranded RNA viruses that are a leading cause of viral gastroenteritis. HAstV particles display T=3 icosahedral symmetry formed by 180 copies of the capsid protein (CP), which undergoes proteolytic maturation to generate infectious HAstV particles. Little is known about the molecular features that govern HAstV particle assembly, maturation, infectivity, and immunogenicity. Here we report the crystal structures of the two main structural domains of the HAstV CP: the core domain at 2.60-Å resolution and the spike domain at 0.95-Å resolution. Fitting of these structures into the previously determined 25-Å-resolution electron cryomicroscopy density maps of HAstV allowed us to characterize the molecular features on the surfaces of immature and mature T=3 HAstV particles. The highly electropositive inner surface of HAstV supports a model in which interaction of the HAstV CP core with viral RNA is a driving force in T=3 HAstV particle formation. Additionally, mapping of conserved residues onto the HAstV CP core and spike domains in the context of the immature and mature HAstV particles revealed dramatic changes to the exposure of conserved residues during virus maturation. Indeed, we show that antibodies raised against mature HAstV have reactivity to both the HAstV CP core and spike domains, revealing for the first time that the CP core domain is antigenic. Together, these data provide new molecular insights into HAstV that have practical applications for the development of vaccines and antiviral therapies.IMPORTANCEAstroviruses are a leading cause of viral diarrhea in young children, immunocompromised individuals, and the elderly. Despite the prevalence of astroviruses, little is known at the molecular level about how the astrovirus particle assembles and is converted into an infectious, mature virus. In this paper, we describe the high-resolution structures of the two main astrovirus capsid proteins. Fitting these structures into previously determined low-resolution maps of astrovirus allowed us to characterize the molecular surfaces of immature and mature astroviruses. Our studies provide the first evidence that astroviruses undergo viral RNA-dependent assembly. We also provide new insight into the molecular mechanisms that lead to astrovirus maturation and infectivity. Finally, we show that both capsid proteins contribute to the adaptive immune response against astrovirus. Together, these studies will help to guide the development of vaccines and antiviral drugs targeting astrovirus.

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Abad, F. Xavier, Cristina Villena, Susana Guix, Santiago Caballero, Rosa M. Pintó, and Albert Bosch. "Potential Role of Fomites in the Vehicular Transmission of Human Astroviruses." Applied and Environmental Microbiology 67, no. 9 (September 1, 2001): 3904–7. http://dx.doi.org/10.1128/aem.67.9.3904-3907.2001.

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ABSTRACT The persistence of human astroviruses dried on representative porous (paper) and nonporous (china) surfaces was investigated. Long-term astrovirus survival on fomites was monitored by an integrated cell culture-reverse transcription-PCR procedure. Viruses were applied to inanimate surfaces in the presence and absence of fecal material, and their survival was assayed at 4 and 20°C with high relative humidity. Astroviruses exhibited a notable persistence when dried on porous and nonporous materials, particularly at low temperature. Short-term survival of astroviruses on fomites was compared to that of other enteric viruses significant for health, such as rotavirus, adenovirus, poliovirus, and hepatitis A virus. Overall, astroviruses persisted better than poliovirus and adenovirus, although they exhibited a shorter survival than rotavirus and hepatitis A virus. Astroviruses show a high level of persistence at the desiccation step, which is of major significance in determining the chance of subsequent virus survival dried on fomites. Astroviruses are able to survive on inert surfaces long enough to suggest that fomites may play a relevant role in the secondary transmission of astrovirus diarrhea.

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Marvin, Shauna A., C. Theodore Huerta, Bridgett Sharp, Pamela Freiden, Troy D. Cline, and Stacey Schultz-Cherry. "Type I Interferon Response Limits Astrovirus Replication and Protects against Increased Barrier PermeabilityIn VitroandIn Vivo." Journal of Virology 90, no. 4 (December 9, 2015): 1988–96. http://dx.doi.org/10.1128/jvi.02367-15.

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ABSTRACTLittle is known about intrinsic epithelial cell responses against astrovirus infection. Here we show that human astrovirus type 1 (HAstV-1) infection induces type I interferon (beta interferon [IFN-β]) production in differentiated Caco2 cells, which not only inhibits viral replication by blocking positive-strand viral RNA and capsid protein synthesis but also protects against HAstV-1-increased barrier permeability. Excitingly, we found similar resultsin vivousing a murine astrovirus (MuAstV) model, providing new evidence that virus-induced type I IFNs may protect against astrovirus replication and pathogenesisin vivo.IMPORTANCEHuman astroviruses are a major cause of pediatric diarrhea, yet little is known about the immune response. Here we show that type I interferon limits astrovirus infection and preserves barrier permeability bothin vitroandin vivo. Importantly, we characterized a new mouse model for studying astrovirus replication and pathogenesis.

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Koci, Matthew D., Bruce S. Seal, and Stacey Schultz-Cherry. "Molecular Characterization of an Avian Astrovirus." Journal of Virology 74, no. 13 (July 1, 2000): 6173–77. http://dx.doi.org/10.1128/jvi.74.13.6173-6177.2000.

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ABSTRACT Astroviruses are known to cause enteric disease in several animal species, including turkeys. However, only human astroviruses have been well characterized at the nucleotide level. Herein we report the nucleotide sequence, genomic organization, and predicted amino acid sequence of a turkey astrovirus isolated from poults with an emerging enteric disease.

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Bosch, A., R. M. Pintó, C. Villena, and F. X. Abad. "Persistence of human astrovirus in fresh and marine water." Water Science and Technology 35, no. 11-12 (June 1, 1997): 243–47. http://dx.doi.org/10.2166/wst.1997.0741.

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Large gastroenteritis outbreaks associated with astroviruses are being reported with increasing frequency suggesting that astrovirus may be an important agent of epidemic acute non-bacterial gastroenteritis in children and adults. In this study, a procedure, based on infection of CaCo-2 cell monolayers followed by reverse-transcription polymerase chain reaction, was developed to ascertain the persistence of infectious human astroviruses in tap and marine water at 4±1°C and 20±1°C. The adequacy of this methodology for monitoring the decay of infectious fastidious viruses was assessed by determining the survival of a cytocidal virus (poliovirus 1) concomitantly by MPNCU and cell infection plus RT-PCR. After 60d in dechlorinated tap water, the decay of astrovirus infectivity was lower than 2 logs at 4±1°C and around 3.6 logs at 20±1°C, while after 90d the titre reduction was around 3.3 and 4.3 logs at 4±1°C and 20±1°C respectively. In natural non-autoclaved seawater at 20°C, astrovirus showed a lower level of persistence. The possibility to acquire data on the survival of fastidious viruses in the environment opens new perspectives on the epidemiology of some health significant infections transmitted by the faecal-oral route.

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Meyer, Lena, Kevin Delgado-Cunningham, Nicholas Lorig-Roach, Jordan Ford, and Rebecca M. DuBois. "Human Astrovirus 1–8 Seroprevalence Evaluation in a United States Adult Population." Viruses 13, no. 6 (May 25, 2021): 979. http://dx.doi.org/10.3390/v13060979.

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Human astroviruses are an important cause of viral gastroenteritis globally, yet few studies have investigated the serostatus of adults to establish rates of previous infection. Here, we applied biolayer interferometry immunosorbent assay (BLI-ISA), a recently developed serosurveillance technique, to measure the presence of blood plasma IgG antibodies directed towards the human astrovirus capsid spikes from serotypes 1–8 in a cross-sectional sample of a United States adult population. The seroprevalence rates of IgG antibodies were 73% for human astrovirus serotype 1, 62% for serotype 3, 52% for serotype 4, 29% for serotype 5, 27% for serotype 8, 22% for serotype 2, 8% for serotype 6, and 8% for serotype 7. Notably, seroprevalence rates for capsid spike antigens correlate with neutralizing antibody rates determined previously. This work is the first seroprevalence study evaluating all eight classical human astrovirus serotypes.

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Méndez-Toss, Martha, Pedro Romero-Guido, Maria Elena Munguía, Ernesto Méndez, and Carlos F. Arias. "Molecular analysis of a serotype 8 human astrovirus genome." Journal of General Virology 81, no. 12 (December 1, 2000): 2891–97. http://dx.doi.org/10.1099/0022-1317-81-12-2891.

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Human astroviruses are an important cause of gastroenteritis. As part of a molecular epidemiological study carried out in Mexico a human astrovirus isolate, Yuc-8, was adapted to grow in CaCo-2 cells, and its entire genome was sequenced. A 15 amino acid deletion in ORF1a, which has been associated with adaptation of astroviruses to grow in cells other than CaCo-2, was present in Yuc-8. Comparative sequence analysis of the Yuc-8 ORF2 with reported human astrovirus sequences revealed that this isolate belongs to genotype (serotype) 8. Two distinct domains in ORF2 were observed: an amino-terminal domain (residues 1 to 415), with identities higher than 81% among the strains analysed, and a carboxy-terminal domain (residues 416 to 782) with identities between 36 and 60%. Two non-superimposable phylogenetic trees were generated by separate analysis of these two domains, suggesting that a differential selective pressure is exerted along the structural polyprotein.

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Lukashov, Vladimir V., and Jaap Goudsmit. "Evolutionary relationships among Astroviridae." Journal of General Virology 83, no. 6 (June 1, 2002): 1397–405. http://dx.doi.org/10.1099/0022-1317-83-6-1397.

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To study the evolutionary relationships among astroviruses, all available sequences for members of the family Astroviridae were collected. Phylogenetic analysis distinguished two deep-rooted groups: one comprising mammalian astroviruses, with ovine astrovirus being an outlier, and the other comprising avian astroviruses. All virus species as well as serotypes of human astroviruses represented individual lineages within the tree. All human viruses clustered together and separately from non-human viruses, which argue for their common evolutionary origin and against ongoing animal-to-human transmissions. The branching order of mammalian astroviruses was exactly the opposite of that of their host species, suggesting at least two cross-species transmissions involving pigs, cats and humans, possibly through intermediate hosts. Analysis of synonymous (Ds) versus non-synonymous (Da) distances revealed that negative selection is dominating in the evolution of astroviruses, with the Ds:Da ratios being up to 46 for the comparisons of the most closely related viruses. Phylogenetic analyses of all open reading frames (ORFs) based on Ds resulted in the loss of tree structures, with virus species – and in ORF2, even serotypes of human astroviruses – branching out from virtually a single node, suggesting their ancient separation. The strong selection against non-synonymous substitutions, the low number of which is, therefore, not proof of a recent separation between lineages, together with the position of the oldest available human astrovirus strain (1971) far from the common node of its serotype 4, suggest that intraserotype diversification originates from an earlier date.

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Janowski, A. B., H. Dudley, T. Feehley, H. Ingle, M. T. Baldridge, H. W. Virgin, R. S. Klein, and D. Wang. "#36: Can Astrovirus VA1, a Novel Human Astrovirus, Cause Diseases of the Central Nervous and Cardiovascular Systems?" Journal of the Pediatric Infectious Diseases Society 10, Supplement_1 (March 1, 2021): S14. http://dx.doi.org/10.1093/jpids/piaa170.041.

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Abstract Background Since their original isolation from human stool samples in 1975, astroviruses have been assumed to be pathogens exclusive to the gastrointestinal tract. However, astroviruses have been recently identified from brain tissue of humans and other mammals suffering from neurological diseases, suggesting that members of this family of viruses have a previously unrecognized neurotropism. One human astrovirus genotype, astrovirus VA1/HMO-C (VA1) is the most frequently identified astrovirus from cases of human encephalitis. We previously described the ability of several cell lines, including Caco-2, A549, and HEK293, to support VA1 growth in cell culture. Our goals were to develop cell culture and animal models to study the pathogenic potential of VA1. Methods VA1 was inoculated into primary astrocytes, primary neurons, and SK-N-SH cells in tissue culture. Viral RNA was measured in multistep growth curves by qRT-PCR, capsid was detected by immunofluorescence, and infectious titer was measured by a TCID50 assay. For development of an in vivo model of infection, mice were inoculated with VA1 with simultaneous intracranial, intraperitoneal, intravenous, and oral gavage inoculations with a VA1 stock. Mice were sacrificed 7 days after inoculation, RNA extracted from tissues, and viral load quantified by qRT-PCR. Tissue was also processed for histology and staining with hematoxylin and eosin. Primary human cardiac endothelial and myocytes were also inoculated with VA1 and viral RNA was measured in multistep growth curves by qRT-PCR. Results We detected the completion of the full VA1 lifecycle in primary astrocytes and SK-N-SH cells with >100-fold increase in viral RNA in a multistep growth curve, detection of intracellular viral capsid, and a >100-fold increase in the infectious titer. These results support the neurotropic potential of VA1. In the development of a mouse model of VA1 infection, we detected the virus in the brain tissue of mice 7 days after inoculation. Unexpectedly, we detected the highest titer of VA1 in heart tissue, which was associated with histological evidence of myocarditis. Furthermore, we demonstrated VA1 can replicate in primary human cardiac endothelial cells but not in primary human cardiac myocytes. Conclusions Our data demonstrate that astroviruses have tissue tropisms outside of the gastrointestinal tract. We provide the first demonstration that cultured neural-derived cells can support infection and replication of astroviruses, providing a model for studying the neuropathogenic potential of VA1. Furthermore, we have identified a novel cardiotropism for VA1, raising the possibility that VA1 may contribute to human cardiac diseases currently without an ascribed etiology.

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Marx, F. E., M. B. Taylor, and W. O. K. Grabow. "Optimization of a PCR method for the detection of astrovirus type 1 in environmental samples." Water Science and Technology 31, no. 5-6 (March 1, 1995): 359–62. http://dx.doi.org/10.2166/wst.1995.0640.

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An improved technique is described that uses the polymerase chain reaction in the detection of astroviruses with much greater sensitivity than existing methods. It is demonstrated to detect human astrovirus serotype 1 in environmental waters from the Pretoria area.

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Vu, Diem-Lan, Aurora Sabrià, Nuria Aregall, Kristina Michl, Virginia Rodriguez Garrido, Lidia Goterris, Albert Bosch, Rosa Maria Pintó, and Susana Guix. "Novel Human Astroviruses: Prevalence and Association with Common Enteric Viruses in Undiagnosed Gastroenteritis Cases in Spain." Viruses 11, no. 7 (June 27, 2019): 585. http://dx.doi.org/10.3390/v11070585.

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A remarkable percentage of acute gastroenteritis cases remain etiologically undiagnosed. The aim of the study was to determine the prevalence of common and emerging enteric viruses, such as novel human astroviruses, among undiagnosed samples from children with acute gastroenteritis. Epidemiological studies for novel human astroviruses are still scarce. Stool samples collected over two consecutive winter seasons (2016–2017) from children with gastroenteritis in Spain, which were negative for bacteria, rotavirus, and adenovirus by routine diagnostics were screened by real-time RT-PCR assays for the presence of classical and novel astrovirus, rotavirus, norovirus GI and GII, sapovirus, and adenovirus. Overall, 220/384 stool samples (57.3%) were positive for at least one virus. Co-infections were identified in 21% of cases. Among a total of 315 viruses identified, adenovirus was the most prevalent (n = 103), followed by rotavirus (n = 51), sapovirus (n = 50), classical astrovirus (n = 43), novel astroviruses (n = 42), and norovirus (n = 26). Novel astroviruses were present in 13.3% of virus-positive cases. Most novel astroviruses were found in children <2-year-old (30/39 children, 77%, p = 0.01) and were found in co-infection (66%). Only classical astroviruses demonstrated significant differences in the Cq values during mono-infections compared to co-infections. In conclusion, common enteric viruses may be frequently found in children with undiagnosed gastroenteritis, indicating the need to implement more sensitive diagnostic methods. Novel astroviruses circulate in the community and could be the cause of gastroenteritis among young children.

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Moser, Lindsey A., and Stacey Schultz-Cherry. "Suppression of Astrovirus Replication by an ERK1/2 Inhibitor." Journal of Virology 82, no. 15 (May 28, 2008): 7475–82. http://dx.doi.org/10.1128/jvi.02193-07.

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ABSTRACT Human astroviruses are nonenveloped, positive-sense single-strand RNA viruses associated with self-limiting diarrhea. Although they are recognized as a leading cause of disease in young children, the cellular factors involved in astrovirus replication are not well defined. The extracellular signal-regulated kinase (ERK) pathway has been shown to regulate many viral infections, but its role during astrovirus infection is unknown. In this report, we show that astrovirus activates ERK1/2 early in infection independently of replication. Inhibition of ERK activation with U0126, a specific ERK inhibitor, significantly reduced viral production. Investigations into the mechanism of ERK1/2 regulation revealed that all steps of the viral life cycle, including early and late protein expression as well as subgenomic and genomic RNA transcription, were diminished during U0126 treatment of monolayers. These data support a role for ERK1/2 in a postattachment step, although the precise mechanism remains under investigation.

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Palombo, Enzo. "Astroviruses as causative agents of gastroenteritis." Microbiology Australia 33, no. 2 (2012): 77. http://dx.doi.org/10.1071/ma12077.

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Astroviruses were first identified over 30 years ago and the virus was soon established as an important cause of gastroenteritis, particularly in young children. Human astrovirus disease was thought to result from infection by a limited number of serotypes. However, recent studies have indicated that the extent of genetic diversity is greater than previously assumed. In addition, the widespread occurrence among animals and reports of recombination and possible cross-species transmission suggest that astroviruses have zoonotic potential.

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Jassim, Morroge, Janan Hasan, and Hassan Hasony. "Human Astrovirus among Children with Cancer in Basrah." Iraqi National Journal of Medicine 1, no. 2 (June 15, 2019): 1–22. http://dx.doi.org/10.37319/iqnjm.1.2.1.

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Background. The impairment of the T-lymphocyte system leads to reduced viral clearance, resulting in intensified disease and the possibility of prolonged infection.(2) The poor functioning of B lymphocytes makes the host susceptible to bacterial and viral infections, especially in cases of malignant disease. Aim of the study. The present study set out to determine the frequency of human astrovirus infection among patients who suffered from malignancies who were being treated in the Oncology Center of the Basrah Children’s Specialty Hospital. Patients and Method. A cross-sectional study was approved for a population of children with cancers during the period from October 1, 2015 through the end of January, 2016. Forty-five children (24 females and 21 males), all with cancers, were admitted to the Oncology Center of Basrah Children’s Specialty Hospital. Their ages ranged from under 1 year to 15 years. According to the results of a specially designed questionnaire, data were obtained from patients who were either symptomatic or asymptomatic for human astrovirus infections, including 3 newly diagnosed cases (before chemotherapy) and 38 cases (during chemotherapy), with the remaining 4 cases admitted after chemotherapy. Ninety stool samples were collected at day 0 and day 4 after admission, and all were tested using astrovirus antigen enzyme-linked immuno sorbent assay (ELISA) kits (EIA-4456). Results. On both days, the rate of astrovirus infections was 15.6% in the hospitalized children with cancers, and there were no statically significant differences between hematological malignancies and solid tumors (P value was 0.857). Among hematological malignancies, astrovirus was detected at a significant rate (the P value was 0.0001) in patients with acute myeloblastic leukemia, while patients with solid tumors exhibited significant expression of rhabdomyosarcoma (the P value was 0.001). Astrovirus infection was more prevalent in females (85.8%) than in males (the P value was 0.001). Infection was most prevalent in the age group of >1–5 years (57%), and most of the infected patients (85.8%) were from rural areas (the P value was 0.012). In most of the symptomatic infected cases (71.4%) the symptom was acute diarrhea (the P value was 0.05), and this was typically during chemotherapy. Conclusion. Astrovirus infections occur at significant rates in acute myeloblastic leukemia, among hematological malignancies, and in patients with rhabdomyosarcoma, in the solid-tumor category. Therefore, astrovirus screening should be done for all children with cancers, and especially for patients with acute myeloblastic leukemia or rhabdomyosarcoma. Keywords: Cancer in children, human astrovirus

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Ulloa, Juan Carlos, and María Fernanda Gutiérrez. "Genomic analysis of two ORF2 segments of new porcine astrovirus isolates and their close relationship with human astroviruses." Canadian Journal of Microbiology 56, no. 7 (July 2010): 569–77. http://dx.doi.org/10.1139/w10-042.

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Porcine astrovirus (PAstV) has been poorly studied and has been associated mainly with gastroenteritis. Computational analysis has revealed the close relationship of PAstV with astroviruses of humans (HAstV) and cats (FAstV). In this study, 105 and 171 stool specimens were collected from piglets and children under 5 years of age, respectively, in different Colombian regions during a 1-year period. The stool samples were examined for astroviruses by ELISA and RT–PCR; 23.8% and 4% were found to be positive for PAstV and HAstV, respectively. Additional sequence analysis with partial sequences obtained from ORF2 identified at least 2 probable groups of PAstVs and possible recombination events between porcine and human astroviruses. This study provides preliminary evidence of the high presence of PAstVs in pigs and proposes the existence of multiple PAstV types that are evolutionarily closely related to HAstVs.

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Méndez, Ernesto, Teresa Fernández-Luna, Susana López, Martha Méndez-Toss, and Carlos F. Arias. "Proteolytic Processing of a Serotype 8 Human Astrovirus ORF2 Polyprotein." Journal of Virology 76, no. 16 (August 15, 2002): 7996–8002. http://dx.doi.org/10.1128/jvi.76.16.7996-8002.2002.

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ABSTRACT Astroviruses require the proteolytic cleavage of the capsid protein to infect the host cell. Here we describe the processing pathway of the primary translation product of the structural polyprotein (ORF2) encoded by a human astrovirus serotype 8 (strain Yuc8). The primary translation product of ORF2 is of approximately 90 kDa, which is subsequently cleaved to yield a 70-kDa protein (VP70) which is assembled into the viral particles. Limited trypsin treatment of purified particles containing VP70 results in the generation of polypeptides VP41 and VP28, which are then further processed to proteins of 38.5, 35, and 34 kDa and 27, 26, and 25 kDa, respectively. VP34, VP27 and VP25 are the predominant proteins in fully cleaved virions, which correlate with the highest level of infectivity. Processing of the VP41 protein to yield VP38.5 to VP34 polypeptides occurred at its carboxy terminus, as suggested by immunoblot analysis using hyperimmune sera to different regions of the ORF2, while processing of VP28 to generate VP27 and VP25 occurred at its carboxy and amino terminus, respectively, as determined by immunoblot, as well as by N-terminal sequencing of those products. Based on these data, the processing pathway for the 90-kDa primary product of astrovirus Yuc8 ORF2 is presented.

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Méndez, Ernesto, M. P. Elizabeth Salas-Ocampo, María Elena Munguía, and Carlos F. Arias. "Protein Products of the Open Reading Frames Encoding Nonstructural Proteins of Human Astrovirus Serotype 8." Journal of Virology 77, no. 21 (November 1, 2003): 11378–84. http://dx.doi.org/10.1128/jvi.77.21.11378-11384.2003.

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ABSTRACT Human astroviruses have a positive-strand RNA genome, which contains three open reading frames (ORF1a, ORF1b, and ORF2). The genomic RNA is translated into two nonstructural polyproteins, nsp1a and nsp1ab, that contain sequences derived from ORF1a and from both ORF1a and ORF1b, respectively. Proteins nsp1a and nsp1ab are thought to be proteolytically processed to yield the viral proteins implicated in the replication of the virus genome; however, the intermediate and final products of this processing have been poorly characterized. To identify the cleavage products of the nonstructural polyproteins of a human astrovirus serotype 8 strain, antisera to selected recombinant proteins were produced and were used to analyze the viral proteins synthesized in astrovirus-infected Caco-2 cells and in cells transfected with recombinant plasmids expressing the ORF1a and ORF1b polyproteins. Pulse-chase experiments identified proteins of approximately 145, 88, 85, and 75 kDa as cleavage intermediates during the polyprotein processing. In addition, these experiments and kinetic analysis of the synthesis of the viral proteins identified polypeptides of 57, 20, and 19 kDa, as well as two products of around 27 kDa, as final cleavage products, with the 57-kDa polypeptide most probably being the virus RNA polymerase and the two ∼27-kDa products being the viral protease. Based on the differential reactivities of the astrovirus proteins with the various antisera used, the individual polypeptides detected were mapped to the virus ORF1a and ORF1b regions.

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Dalton, Rosa M., Esperanza P. Pastrana, and Alicia Sánchez-Fauquier. "Vaccinia Virus Recombinant Expressing an 87-Kilodalton Polyprotein That Is Sufficient To Form Astrovirus-Like Particles." Journal of Virology 77, no. 16 (August 15, 2003): 9094–98. http://dx.doi.org/10.1128/jvi.77.16.9094-9098.2003.

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ABSTRACT Human astrovirus is an important cause of acute gastroenteritis. We have generated, for the first time, a vaccinia virus recombinant expressing the astrovirus 87-kDa structural polyprotein. The results demonstrate that this expression results in the formation of virus-like particles in the absence of other astrovirus proteins and genomic RNA. The purified trypsin-activated virus-like particles strongly resemble the complete astrovirus particles.

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Toh, Yukimatsu, Justin Harper, Kelly A. Dryden, Mark Yeager, Carlos F. Arias, Ernesto Méndez, and Yizhi J. Tao. "Crystal Structure of the Human Astrovirus Capsid Protein." Journal of Virology 90, no. 20 (July 27, 2016): 9008–17. http://dx.doi.org/10.1128/jvi.00694-16.

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ABSTRACTHuman astrovirus (HAstV) is a leading cause of viral diarrhea in infants and young children worldwide. HAstV is a nonenveloped virus with a T=3 capsid and a positive-sense RNA genome. The capsid protein (CP) of HAstV is synthesized as a 90-kDa precursor (VP90) that can be divided into three linear domains: a conserved N-terminal domain, a hypervariable domain, and an acidic C-terminal domain. Maturation of HAstV requires proteolytic processing of the astrovirus CP both inside and outside the host cell, resulting in the removal of the C-terminal domain and the breakdown of the rest of the CP into three predominant protein species with molecular masses of ∼34, 27/29, and 25/26 kDa, respectively. We have now solved the crystal structure of VP9071–415(amino acids [aa] 71 to 415 of VP90) of human astrovirus serotype 8 at a 2.15-Å resolution. VP9071–415encompasses the conserved N-terminal domain of VP90 but lacks the hypervariable domain, which forms the capsid surface spikes. The structure of VP9071–415is comprised of two domains: an S domain, which adopts the typical jelly-roll β-barrel fold, and a P1 domain, which forms a squashed β-barrel consisting of six antiparallel β-strands similar to what was observed in the hepatitis E virus (HEV) capsid structure. Fitting of the VP9071–415structure into the cryo-electron microscopy (EM) maps of HAstV produced an atomic model for a continuous, T=3 icosahedral capsid shell. Our pseudoatomic model of the human HAstV capsid shell provides valuable insights into intermolecular interactions required for capsid assembly and trypsin-mediated proteolytic maturation needed for virus infectivity. Such information has potential applications in the development of a virus-like particle (VLP) vaccine as well as small-molecule drugs targeting astrovirus assembly/maturation.IMPORTANCEHuman astrovirus (HAstV) is a leading cause of viral diarrhea in infants and young children worldwide. As a nonenveloped virus, HAstV exhibits an intriguing feature in that its maturation requires extensive proteolytic processing of the astrovirus capsid protein (CP) both inside and outside the host cell. Mature HAstV contains three predominant protein species, but the mechanism for acquired infectivity upon maturation is unclear. We have solved the crystal structure of VP9071–415of human astrovirus serotype 8. VP9071–415encompasses the conserved N-terminal domain of the viral CP. Fitting of the VP9071–415structure into the cryo-EM maps of HAstV produced an atomic model for the T=3 icosahedral capsid. Our model of the HAstV capsid provides valuable insights into intermolecular interactions required for capsid assembly and trypsin-mediated proteolytic maturation. Such information has potential applications in the development of a VLP vaccine as well as small-molecule drugs targeting astrovirus assembly/maturation.

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Babkin, Igor V., Artem Y. Tikunov, Elena V. Zhirakovskaia, Sergei V. Netesov, and Nina V. Tikunova. "High evolutionary rate of human astrovirus." Infection, Genetics and Evolution 12, no. 2 (March 2012): 435–42. http://dx.doi.org/10.1016/j.meegid.2012.01.019.

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Risco, C., J. L. Carrascosa, A. M. Pedregosa, C. D. Humphrey, and A. Sanchez-Fauquier. "Ultrastructure of human astrovirus serotype 2." Journal of General Virology 76, no. 8 (August 1, 1995): 2075–80. http://dx.doi.org/10.1099/0022-1317-76-8-2075.

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Mendez, E., C. Munoz-Yanez, C. Sanchez-San Martin, G. Aguirre-Crespo, M. d. R. Banos-Lara, M. Gutierrez, R. Espinosa, et al. "Characterization of Human Astrovirus Cell Entry." Journal of Virology 88, no. 5 (December 11, 2013): 2452–60. http://dx.doi.org/10.1128/jvi.02908-13.

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I Naif, Amal, Areej A Hussein, Mohammed J Shaker, and Rawaa A Hussein. "Human Astrovirus and Cryptosporidium Co-infection among Children with Gastroenteritis in Diyala Governorate." Diyala Journal of Medicine 19, no. 2 (December 15, 2020): 66–77. http://dx.doi.org/10.26505/djm.19025440627.

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Background: Gastroenteritis is the second leading cause of death in children under five years old. The highest mortality from diarrheal diseases in children lived crowded areas were poor sanitary and hygienic conditions found. Objective: To determine the co-infections between human astrovirus and Cryptosporidium spp. among children with gastroenteritis below 5 years of age in the Diyala governorate. Patients and Methods: A cross-sectional study was carried out for 100 patients with acute gastroenteritis who attended the Emergency Department of Pediatrics in Al-Batool Teaching Hospital for Maternity and Pediatric in Baqubah city, during the period from July 2019 to February 2020. Real time-PCR was used to detect human astrovirus while enzyme- linked immunosorbent assay was used to detect Cryptosporidium spp. A specific formula sheet was used to collect demographic data such as age, gender, mother education, and type of milk feeding. Results: Out of 100 samples, 14 samples were positive for human astrovirus and 38 samples were positive for Cryptosporidium. The infection rate is more common in males (9 cases) (25cases) rather than females, and in age group less than years 11(78.58%) and 34(89.47%) respectively. Artificial feeding showed higher frequencies of infection than others in the study population. Co-infection astrovirus and Cryptosporidium found in four patients, all of whom were males aged under one-year and the difference was statistically significant with all parameters. Conclusion: A high proportion of positive cases for human astrovirus and Cryptosporidium spp. were notes in males and the age group less than one year’s co-infection showed high frequency in the study population. Keywords: Gastroenteritis, human astrovirus, Cryptosporidium, co-infection

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Xavier, Maria da Penha Trindade Pinheiro, Filipe Aníbal Carvalho Costa, Mônica Simões Rocha, Juliana da Silva Ribeiro de Andrade, Fernanda Kreischer Bandeira Diniz, Thais Ramos de Andrade, Marize Pereira Miagostovich, José Paulo Gagliardi Leite, and Eduardo de Mello Volotão. "Surveillance of Human Astrovirus Infection in Brazil: The First Report of MLB1 Astrovirus." PLOS ONE 10, no. 8 (August 14, 2015): e0135687. http://dx.doi.org/10.1371/journal.pone.0135687.

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Geigenmüller, Ute, Teri Chew, Nancy Ginzton, and Suzanne M. Matsui. "Processing of Nonstructural Protein 1a of Human Astrovirus." Journal of Virology 76, no. 4 (February 15, 2002): 2003–8. http://dx.doi.org/10.1128/jvi.76.4.2003-2008.2002.

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ABSTRACT Astrovirus contains three open reading frames (ORF) on its genomic RNA, ORF1a, ORF1b, and ORF2. ORF1a encodes a 920-amino-acid (aa) nonstructural protein, nsP1a, which displays a 3C-like serine protease motif. Little is known about the processing of nsP1a or whether the protease it contains is active and involved in autocatalytic processing. Here we address both of these matters. Intact and N-terminally deleted forms of ORF1a from human astrovirus serotype 1 were expressed in BHK cells, and nsP1a-derived processing products were immunoprecipitated with an nsP1a-specific antibody or an antibody specific for an N-terminally linked epitope tag. The mapping of the main processing products, p20 and p27, suggests cleavage sites near aa 170, 410, and 655 of nsP1a. Cleavages at around aa 410 and 655, but not aa 170, were abolished when a 9-aa substitution was introduced into the protease motif in nsP1a. The p27 processing product was also found in Caco-2 cells that had been infected with human astrovirus serotype 1, confirming the presence of the cleavage sites at approximately aa 410 and 655.

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Cortez, Valerie, Bridgett Sharp, Brandi Livingston, Hannah Rowe, Ramzi Alsallaq, Jason Rosch, Elisa Margolis, and Stacey Schultz-Cherry. "13 ASTROVIRUS ALTERS THE GUT MUCUS BARRIER AND REDUCES COLONIZATION TO ENTEROPATHOGENIC E. COLI." Inflammatory Bowel Diseases 26, Supplement_1 (January 2020): S28. http://dx.doi.org/10.1093/ibd/zaa010.066.

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Abstract Goblet cells, specialized epithelial cells that produce mucus, are essential for gut health. Dysfunctional goblet cell secretion can weaken the mucus barrier, bringing commensal microbes and other lumenal contents in contact with the epithelial barrier, triggering inflammation. We recently discovered that murine astroviruses infect goblet cells in the small intestine, making it the first enteric virus in which this tropism has been recognized in vivo. To first determine whether astrovirus infection alters mucus production in goblet cells, we used periodic acid-Schiff staining of small intestinal tissues and found a thicker mucus layer in infected compared to mock-infected animals (1.85 to 2.51-fold, p<0.001). Because changes to the mucus barrier can alter the microbial environment in the gut, we used 16S metagenomic to characterize the microbiome after infection. We found that the relative frequency of well-characterized mucus-degrading bacteria significantly increased after infection (p<0.001). Using phylogenetic edge principal components analysis, we also identified distinct microbiome shifts between 0 and 14 days post-infection, corresponding to peak infection. Finally, to determine the extent to which these changes in the mucus barrier could have a functional consequence to host disease susceptibility, we developed a neonatal model for astrovirus and tested whether animals inoculated with enteropathogenic E. coli (EPEC), an adherent bacterial pathogen, would be protected from colonization. In comparison to animals inoculated with EPEC alone, co-infected animals had significantly reduced EPEC colonization (p<0.01). Together, these studies reveal a new avenue of enteric virus regulation of gut homeostasis and immunity via goblet cells and highlight astroviruses as a novel model to study the mucus barrier. Future studies are needed to determine whether astrovirus-induced increases in the mucus barrier protect from other gastrointestinal diseases and how these data translate to human astroviruses, which predominately infect children <1-year-old and coincides with the development of gut immunity.

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Lawler, Patricia E., Kirstin A. Cook, Hannah G. Williams, Linda L. Archer, Karen E. Schaedel, Natalie M. Isaza, and James F. X. Wellehan. "Determination of the diversity of astroviruses in feces from cats in Florida." Journal of Veterinary Diagnostic Investigation 30, no. 2 (December 4, 2017): 275–79. http://dx.doi.org/10.1177/1040638717747322.

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Astroviruses are small, nonenveloped RNA viruses that have been linked to numerous diseases in a variety of species, including enteric disease in humans and cheetahs. Species Mamastrovirus 2, previously known as feline astrovirus, has been isolated from the feces of domestic cats and cheetahs. A total of 122 cat fecal samples from Alachua County, FL Animal Services and the Veterinary Community Outreach Program at the University of Florida were analyzed, and 35 contained astroviral RNA that was amplified and identified using consensus RT-PCR and sequence analysis. Using phylogenetic analysis, 19 of the astroviral sequences were identified as Mamastrovirus 2, making it the most prevalent astrovirus in this population. Three samples were identified as an astrovirus similar to viruses previously identified in foxes in The Netherlands and a cat in California, and one was similar to a bat astrovirus. One astroviral sequence was identified as an Avastrovirus. Although a causative relationship between mamastroviruses and enteric disease in cats has yet to be established, it is clear that mamastroviruses are prevalent, and an understanding of prevalence of astroviral types may help direct future test development.

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Aguilar-Hernández, Nayeli, Susana López, and Carlos F. Arias. "Minimal capsid composition of infectious human astrovirus." Virology 521 (August 2018): 58–61. http://dx.doi.org/10.1016/j.virol.2018.05.021.

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JAKAB, FERENC, JÁNOS PÉTERFAI, TIBOR VEREBÉLY, EDINA MELEG, KRISZTIÁN BÁNYAI, DOUGLAS K. MITCHELL, and GYÖRGY SZÛCS. "Human astrovirus infection associated with childhood intussusception." Pediatrics International 49, no. 1 (February 2007): 103–5. http://dx.doi.org/10.1111/j.1442-200x.2007.02293.x.

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Willcocks, M. M., T. D. K. Brown, C. R. Madeley, and M. J. Carter. "The complete sequence of a human astrovirus." Journal of General Virology 75, no. 7 (July 1, 1994): 1785–88. http://dx.doi.org/10.1099/0022-1317-75-7-1785.

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Ykema, Matthew, and Yizhi J. Tao. "Structural Insights into the Human Astrovirus Capsid." Viruses 13, no. 5 (May 1, 2021): 821. http://dx.doi.org/10.3390/v13050821.

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Astroviruses (AstVs) are non-enveloped, positive single-stranded RNA viruses that cause a wide range of inflammatory diseases in mammalian and avian hosts. The T = 3 viral capsid is unique in its ability to infect host cells in a process driven by host proteases. Intercellular protease cleavages allow for viral egress from a cell, while extracellular cleavages allow for the virus to enter a new host cell to initiate infection. High-resolution models of the capsid core indicate a large, exposed region enriched with protease cleavage sites. The virus spike protein allows for binding to target cells and is the major target for naturally occurring and engineered neutralizing antibodies. During maturation, the capsid goes through significant structural changes including the loss of many surface spikes. The capsid interacts with host membranes during the virus life cycle at multiple stages such as assembly, host cell entry and exit. This review will cover recent findings and insights related to the structure of the capsid and its function. Further understanding of the viral capsid structure and maturation process can contribute to new vaccines, gastric therapeutics, and viral engineering applications.

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Fuentes, Cristina, Albert Bosch, Rosa M. Pintó, and Susana Guix. "Identification of Human Astrovirus Genome-Linked Protein (VPg) Essential for Virus Infectivity." Journal of Virology 86, no. 18 (July 11, 2012): 10070–78. http://dx.doi.org/10.1128/jvi.00797-12.

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Viral genome-linked proteins (VPgs) have been identified in several single-stranded positive-sense RNA virus families. The presence of such protein in the familyAstroviridaehas not been fully elucidated, although a putative VPg coding region in open reading frame 1a (ORF1a) of astrovirus with high amino acid sequence similarity to the VPg coding region ofCaliciviridaehas been previously identified. In this work we present several experimental findings that show that human astrovirus (HAstV) RNA encodes a VPg essential for viral infectivity: (i) RNase treatment of RNA purified from astrovirus-infected cells results in a single protein of 13 to 15 kDa, compatible with the predicted astrovirus VPg size; (ii) the antibody used to detect this 13- to 15-kDa protein is specifically directed against a region that includes the putative VPg coding region; (iii) the 13- to 15-kDa protein detected has been partially sequenced and the sequence obtained is contained in the computationally predicted VPg; (iv) the protein resulting from this putative VPg coding region is a highly disordered protein, resembling the VPg of sobemo-, calici- and potyviruses; (v) proteolytic treatment of the genomic RNA leads to loss of infectivity; and (vi) mutagenesis of Tyr-693 included in the putative VPg protein is lethal for HAstV replication, which strongly supports its functional role in the covalent link with the viral RNA.

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Kriston, S., M. M. Willcocks, M. J. Carter, and W. D. Cubitt. "Seroprevalence of astrovirus types 1 and 6 in London, determined using recombinant virus antigen." Epidemiology and Infection 117, no. 1 (August 1996): 159–64. http://dx.doi.org/10.1017/s0950268800001266.

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SummaryWe have developed a microimmunofluorescence test (IF) which uses cells infected with a recombinant baculovirus which expresses the capsid proteins of astrovirus types 1 or 6. The IF test was sensitive and specific and the results for human astrovirus type 1 (HAst-1) were comparable to those obtained by immune electronmicroscopy and radioimmunoassay. Application of the test to a panel of 273 sera collected from patients and staff at two childrens hospitals in London showed that over 50% of the population were infected by Hast-1 between the age of 5 and 12 months rising to 90% by 5 years, whereas human astrovirus type 6 (HAst6) was relatively uncommon (10–30%) in all age groups.

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Niendorf, Sandra, Dominik Harms, Katja F. Hellendahl, Elisa Heuser, Sindy Böttcher, Sonja Jacobsen, C. Thomas Bock, and Rainer G. Ulrich. "Presence and Diversity of Different Enteric Viruses in Wild Norway Rats (Rattus norvegicus)." Viruses 13, no. 6 (May 26, 2021): 992. http://dx.doi.org/10.3390/v13060992.

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Rodents are common reservoirs for numerous zoonotic pathogens, but knowledge about diversity of pathogens in rodents is still limited. Here, we investigated the occurrence and genetic diversity of enteric viruses in 51 Norway rats collected in three different countries in Europe. RNA of at least one virus was detected in the intestine of 49 of 51 animals. Astrovirus RNA was detected in 46 animals, mostly of rat astroviruses. Human astrovirus (HAstV-8) RNA was detected in one, rotavirus group A (RVA) RNA was identified in eleven animals. One RVA RNA could be typed as rat G3 type. Rat hepatitis E virus (HEV) RNA was detected in five animals. Two entire genome sequences of ratHEV were determined. Human norovirus RNA was detected in four animals with the genotypes GI.P4-GI.4, GII.P33-GII.1, and GII.P21. In one animal, a replication competent coxsackievirus A20 strain was detected. Additionally, RNA of an enterovirus species A strain was detected in the same animal, albeit in a different tissue. The results show a high detection rate and diversity of enteric viruses in Norway rats in Europe and indicate their significance as vectors for zoonotic transmission of enteric viruses. The detailed role of Norway rats and transmission pathways of enteric viruses needs to be investigated in further studies.

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Davis, Amy E., Virginia Hargest, Shaoyuan Tan, Qidong Jia, Valerie Cortez, and Stacey Schultz-Cherry. "#51: Neurotropic Astrovirus-VA1: Identifying the distinctions from classical genotypes." Journal of the Pediatric Infectious Diseases Society 10, Supplement_2 (June 1, 2021): S15—S16. http://dx.doi.org/10.1093/jpids/piab031.034.

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Abstract Background Human astroviruses (HAstV) are a leading cause of acute gastroenteritis in children, particularly those under the age of 2 or with immunosuppressive conditions. Indeed, our studies suggest that children with hematological malignancies are at high risk of infection. However, it has become increasingly clear that HAstV infections can also be associated with respiratory and even central nervous system (CNS) diseases. In the last decade, there have been at least 12 cases of astrovirus-induced CNS disease resulting in encephalitis and meningitis, including 2 St Jude patients. The CNS-associated infections are overwhelmingly fatal and are primarily caused by a novel astrovirus genotype, VA1, that is genetically more similar to animal astroviruses that also induce CNS-associated infections. The recent ability to propagate the VA1 strain in cell lines affords us the opportunity to better understand VA1 infection and how it compares to the better-studied HAstV1 strain. Methods Viral kinetics were determined by infection of human intestinal adenocarcinoma Caco-2 cells with either HAstV1 or VA1 and monitored for 24 hours post-infection (hpi). Infected cells were identified via immunofluorescent microscopy using antibodies against double-stranded RNA and viral capsid. Epithelial permeability of astrovirus-infected Caco-2 cells was measured using transepithelial electrical resistance (TER) and monitored for 24hpi. Nitazoxanide efficacy was identified by immunofluorescent analysis as described previously. Results Our findings demonstrate that HAstV1 and VA1 replicate in intestinal epithelial cells without inducing cell death or a pro-inflammatory cytokine response. However, these two strains have distinct replication kinetics. VA1 appears to have an ~8 hour lag in the expression of dsRNA and capsid protein compared to HAstV1 and does not require exogenous proteases to process the viral outer coat (capsid) protein, Additionally, we demonstrated that the increase in epithelial barrier permeability associated with HAstV1-infection is not found in VA1-infected cells, which is intriguing and may explain why HAstV1 is more likely to cause diarrhea. Of clinical importance, we have revealed a similar susceptibility of VA1 to the antiviral drug, nitazoxanide, which we have recently demonstrated its effectiveness inhibiting classical HAstV strains. Conclusion Overall, our studies highlight that VA1 pathogenesis is distinct from HAstV1, which could explain the differences in vivo. Future studies will be necessary to investigate viral replication and pathogenesis in distinct neuronal cells and in vivo.

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Liste, Mary B., Ivelisse Natera, José A. Suarez, Flor H. Pujol, Ferdinando Liprandi, and Juan E. Ludert. "Enteric Virus Infections and Diarrhea in Healthy and Human Immunodeficiency Virus-Infected Children." Journal of Clinical Microbiology 38, no. 8 (2000): 2873–77. http://dx.doi.org/10.1128/jcm.38.8.2873-2877.2000.

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Forty-three stool samples from 27 human immunodeficiency virus (HIV)-seropositive children and 38 samples from 38 HIV-negative children, collected during a 15-month period, were examined for enteric viruses. Diagnostic assays included enzyme immunoassays for rotavirus, adenovirus, and Norwalk virus; polyacrylamide gel electrophoresis for picobirnavirus and atypical rotavirus; and PCR for astrovirus and enterovirus. Specimens from HIV-positive children were more likely than those of HIV-negative children to have enterovirus (56 versus 21%;P < 0.0002) and astrovirus (12 versus 0%;P < 0.02), but not rotavirus (5 versus 8%;P > 0.5). No adenoviruses, picobirnaviruses, or Norwalk viruses were found. The rates of virus-associated diarrhea were similar among HIV-positive and HIV-negative children. Enteroviruses were excreted for up to 6 months in HIV-positive children; however, no evidence for prolonged excretion of poliovirus vaccine was observed. These results suggest that although infection with enterovirus and astrovirus may be frequent in HIV-infected children, enteric viruses are not associated with the diarrhea frequently suffered by these children.

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Papaventsis, Dimitrios C., Winifred Dove, Nigel A. Cunliffe, Osamu Nakagomi, Patrice Combe, Pierre Grosjean, and C. Anthony Hart. "Human Astrovirus Gastroenteritis in Children, Madagascar, 2004–2005." Emerging Infectious Diseases 14, no. 5 (May 2008): 844–46. http://dx.doi.org/10.3201/eid1405.070563.

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Guo, Li, Richard Gonzalez, Wei Wang, Yongjun Li, Glaucia Paranhos-Baccala, Guy Vernet, and Jianwei Wang. "Complete genome sequence of human astrovirus genotype 6." Virology Journal 7, no. 1 (2010): 29. http://dx.doi.org/10.1186/1743-422x-7-29.

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46

Kiang, David, and Suzanne M. Matsui. "Proteolytic processing of a human astrovirus nonstructural protein." Journal of General Virology 83, no. 1 (January 1, 2002): 25–34. http://dx.doi.org/10.1099/0022-1317-83-1-25.

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Abstract:

To analyse the activity of the putative 3C-like serine protease encoded in open reading frame (ORF)-1a of human astrovirus serotype 1 (HAstV-1), ORF-1a was transcribed and translated in vitro. Translation products, identified by immunoprecipitation with specific antibodies against recombinant C-terminal ORF-1a fragments, include the full-length 101 kDa (p101) protein and a 38 kDa band (p38). In addition, a 64 kDa protein (p64) was immunoprecipitated by an anti-FLAG antibody when a FLAG epitope was inserted at the N terminus of the ORF-1a product. Mutation of the amino acids predicted to form the catalytic triad of the HAstV-1 3C-like serine protease (Ser-551, Asp-489, His-461) resulted in undetectable levels of p38, supporting the involvement of the HAstV-1 3C-like serine protease and the importance of these amino acids in the processing of p101 into p38 and p64. N-terminal deletions of up to 420 aa of p101 that did not involve the predicted 3C-like serine protease motif did not alter levels of p38 compared to wild-type. C-terminal deletion analysis localized p38 to the C terminus of ORF-1a. Mutation of the P1 residue of the predicted cleavage site, which is conserved among known human and sheep astrovirus sequences, resulted in no detectable p38, supporting cleavage at the Gln-567↓Thr-568 dipeptide. These results suggest that p101 is cleaved into an N-terminal p64 fragment and a C-terminal p38 product at Gln-567↓Thr-568 in a process that is dependent on the viral 3C-like serine protease.

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Matsui, S. M., J. P. Kim, H. B. Greenberg, L. M. Young, L. S. Smith, T. L. Lewis, J. E. Herrmann, N. R. Blacklow, K. Dupuis, and G. R. Reyes. "Cloning and characterization of human astrovirus immunoreactive epitopes." Journal of Virology 67, no. 3 (1993): 1712–15. http://dx.doi.org/10.1128/jvi.67.3.1712-1715.1993.

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Dong, J., L. Dong, E. Mendez, and Y. Tao. "Crystal structure of the human astrovirus capsid spike." Proceedings of the National Academy of Sciences 108, no. 31 (July 18, 2011): 12681–86. http://dx.doi.org/10.1073/pnas.1104834108.

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Bass, D. M., and U. Upadhyayula. "Characterization of human serotype 1 astrovirus-neutralizing epitopes." Journal of virology 71, no. 11 (1997): 8666–71. http://dx.doi.org/10.1128/jvi.71.11.8666-8671.1997.

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Lizasoain, A., L. F. L. Tort, M. García, M. M. Gómez, J. Cristina, J. P. G. Leite, M. P. Miagostovich, M. Victoria, and R. Colina. "Environmental Assessment of Classical Human Astrovirus in Uruguay." Food and Environmental Virology 7, no. 2 (February 14, 2015): 142–48. http://dx.doi.org/10.1007/s12560-015-9186-4.

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Journal articles on the topic 'Human Astrovirus'

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