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Stacey Schultz-cherry - One of the best experts on this subject based on the ideXlab platform.
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Astrovirus Replication Is Inhibited by Nitazoxanide In Vitro and In Vivo.
Journal of virology, 2020Co-Authors: Virginia Hargest, Valerie Cortez, Bridgett Sharp, Brandi Livingston, Stacey Schultz-cherryAbstract:Astroviruses (AstV) are a leading cause of diarrhea, especially in the very young, the elderly, and immunocompromised populations. Despite their significant impact on public health, no drug therapies for Astrovirus have been identified. In this study, we fill this gap in knowledge and demonstrate that the FDA-approved broad-spectrum anti-infective drug nitazoxanide (NTZ) blocks Astrovirus replication in vitro with a 50% effective concentration (EC50) of approximately 1.47 μM. It can be administered up to 8 h postinfection and is effective against multiple human Astrovirus serotypes, including clinical isolates. Most importantly, NTZ reduces viral shedding in vivo, exhibiting its potential as a future clinical therapeutic.IMPORTANCE Human Astroviruses (HAstV) are thought to cause between 2 and 9% of acute, nonbacterial diarrhea cases in children worldwide. HAstV infection can be especially problematic in immunocompromised people and infants, where the virus has been associated with necrotizing enterocolitis and severe and persistent diarrhea, as well as rare instances of systemic and fatal disease. And yet, no antivirals have been identified to treat Astrovirus infection. Our study provides the first evidence that nitazoxanide may be an effective therapeutic strategy against Astrovirus disease.
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Astrovirus and the microbiome.
Current opinion in virology, 2019Co-Authors: Valerie Cortez, Elisa Margolis, Stacey Schultz-cherryAbstract:Although Astroviruses are most commonly associated with acute gastrointestinal illness in humans, their ability to infect a broad range of hosts and cause a spectrum of disease makes them widespread and complex pathogens. The precise mechanisms that dictate the course of Astrovirus disease have not been studied extensively but are likely driven by multifactorial host-microbe interactions. Recent insights from studies of animal Astrovirus infections have revealed both beneficial and detrimental effects for the host. However, further in-depth studies are needed to fully explore the consequences of Astrovirus-induced changes in the gut microenvironment as well as the role of the microbiota in Astrovirus infection.
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Astrovirus Pathogenesis.
Viruses, 2017Co-Authors: Cydney Johnson, Virginia Hargest, Valerie Cortez, Victoria A Meliopoulos, Stacey Schultz-cherryAbstract:Astroviruses are a major cause of diarrhea in the young, elderly, and the immunocompromised. Since the discovery of human Astrovirus type 1 (HAstV-1) in 1975, the family Astroviridae has expanded to include two more human clades and numerous mammalian and avian-specific genotypes. Despite this, there is still little known about pathogenesis. The following review highlights the current knowledge of Astrovirus pathogenesis, and outlines the critical steps needed to further Astrovirus research, including the development of animal models of cell culture systems.
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Type I Interferon Response Limits Astrovirus Replication and Protects Against Increased Barrier Permeability in vitro and in vivo
Journal of virology, 2015Co-Authors: Shauna A. Marvin, Troy Cline, Pamela Freiden, C. Theodore Huerta, Bridgett Sharp, Stacey Schultz-cherryAbstract:ABSTRACT Little 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 results in vivo using a murine Astrovirus (MuAstV) model, providing new evidence that virus-induced type I IFNs may protect against Astrovirus replication and pathogenesis in vivo . IMPORTANCE Human 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 both in vitro and in vivo . Importantly, we characterized a new mouse model for studying Astrovirus replication and pathogenesis.
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Crystal Structure of the Avian Astrovirus Capsid Spike
Journal of virology, 2013Co-Authors: Rebecca M. Dubois, Pamela Freiden, Shauna A. Marvin, Muralidhar Reddivari, Richard J. Heath, S.w. White, Stacey Schultz-cherryAbstract:Astroviruses are small, nonenveloped, single-stranded RNA viruses that cause diarrhea in a wide variety of mammals and birds. On the surface of the viral capsid are globular spikes that are thought to be involved in attachment to host cells. To understand the basis of species specificity, we investigated the structure of an avian Astrovirus capsid spike and compared it to a previously reported human Astrovirus capsid spike structure. Here we report the crystal structure of the turkey Astrovirus 2 (TAstV-2) capsid surface spike domain, determined to 1.5-A resolution, and identify three conserved patches on the surface of the spike that are candidate avian receptor-binding sites. Surprisingly, the overall TAstV-2 capsid spike structure is unique, with only distant structural similarities to the human Astrovirus capsid spike and other viral capsid spikes. There is an absence of conserved putative receptor-binding sites between the human and avian spikes. However, there is evidence for carbohydrate-binding sites in both human and avian spikes, and studies with human Astrovirus 1 (HAstV-1) suggest a minor role in infection for chondroitin sulfate but not heparin. Overall, our structural and functional studies provide new insights into Astrovirus host cell entry, species specificity, and evolution.
Matthew D. Koci - One of the best experts on this subject based on the ideXlab platform.
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oral administration of Astrovirus capsid protein is sufficient to induce acute diarrhea in vivo
Mbio, 2016Co-Authors: Victoria A Meliopoulos, Pamela Freiden, Shauna A. Marvin, Prashant K. Nighot, Rizwana Ali, Anthony T. Blikslager, Lindsey A. Moser, Muralidhar Reddivari, Richard J. Heath, Matthew D. KociAbstract:ABSTRACT The disease mechanisms associated with the onset of Astrovirus diarrhea are unknown. Unlike other enteric virus infections, Astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human Astrovirus serotype 1 (HAstV-1) capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey Astrovirus 2 (TAstV-2) capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, Astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the Astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction. IMPORTANCE Acute gastroenteritis, with its sequela diarrhea, is one of the most important causes of childhood morbidity and mortality worldwide. A variety of infectious agents cause gastroenteritis, and in many cases, an enterotoxin produced by the agent is involved in disease manifestations. Although we commonly think of bacteria as a source of toxins, at least one enteric virus, rotavirus, produces a protein with enterotoxigenic activity during viral replication. In these studies, we demonstrate that oral administration of the turkey Astrovirus 2 (TAstV-2) structural (capsid) protein induces acute diarrhea, increases barrier permeability, and causes relocalization of NHE3 in the small intestine, suggesting that rotavirus may not be alone in possessing enterotoxigenic activity.
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Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea In Vivo
American Society for Microbiology, 2016Co-Authors: Victoria A Meliopoulos, Pamela Freiden, Shauna A. Marvin, Prashant K. Nighot, Rizwana Ali, Anthony T. Blikslager, Lindsey A. Moser, Muralidhar Reddivari, Richard J. Heath, Matthew D. KociAbstract:The disease mechanisms associated with the onset of Astrovirus diarrhea are unknown. Unlike other enteric virus infections, Astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human Astrovirus serotype 1 (HAstV-1) capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey Astrovirus 2 (TAstV-2) capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, Astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the Astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction
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Astrovirus infection induces sodium malabsorption and redistributes sodium hydrogen exchanger expression
Virology, 2010Co-Authors: Prashant K. Nighot, Adam J. Moeser, Rizwana Ali, Anthony T. Blikslager, Matthew D. KociAbstract:Astroviruses are known to be a leading cause of diarrhea in infants and the immunocompromised; however, our understanding of this endemic pathogen is limited. Histological analyses of Astrovirus pathogenesis demonstrate clinical disease is not associated with changes to intestinal architecture, inflammation, or cell death. Recent studies in vitro have suggested that Astroviruses induce actin rearrangement leading to loss of barrier function. The current study used the type-2 turkey Astrovirus (TAstV-2) and turkey poult model of Astrovirus disease to examine how Astrovirus infection affects the ultrastructure and electrophysiology of the intestinal epithelium. These data demonstrate that infection results in changes to the epithelial ultrastructure, rearrangement of F-actin, decreased absorption of sodium, as well as redistribution of the sodium/hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm. Collectively, these data suggest Astrovirus infection induces sodium malabsorption, possibly through redistribution of specific sodium transporters, which results in the development of an osmotic diarrhea.
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Astrovirus-Induced Synthesis of Nitric Oxide Contributes to Virus Control during Infection
Journal of virology, 2004Co-Authors: Matthew D. Koci, Laura A. Kelley, Diane Larsen, Stacey Schultz-cherryAbstract:Astroviruses were first identified in infants with diarrhea in 1975 by Madeley and Cosgrove (C. R. Madeley and B. P. Cosgrove, Letter, Lancet ii:451-452, 1975) and are now recognized as one of the leading causes of childhood diarrhea worldwide. By the age of five, 90% of children have antibodies against Astroviruses (17, 25). In addition to their endemic nature, Astroviruses also cause outbreaks of enteritis in schools, geriatric care facilities, children's hospitals, and in immunocompromised individuals (25). In fact, the elderly and the immunocompromised, such as AIDS patients, represent an expanding demographic of Astrovirus disease (30). Astroviruses are transmitted mainly through a fecal-oral route (24). The virus typically has an incubation period of 1 to 4 days and causes an acute gastroenteritis which lasts approximately 4 days (9). Diarrhea is the most common symptom; however, vomiting, abdominal distention, and dehydration can occur (25). Much of what is known about Astrovirus-mediated disease comes from epidemiological studies involving routine surveillance for enteric disease agents, following outbreaks, and serologic studies. Observational data from human samples and serological surveys suggest that antibodies are the key mediators of protection (18). However, there is nothing known about the role of the innate or cellular immune responses in Astrovirus resistance. This is due to the lack of a small-animal model for Astrovirus infection. We developed a small-animal model using turkey Astrovirus type-2 (North Carolina/034/1999) (TAstV-2) to study the mechanisms of viral pathogenesis and immune protection (3, 14, 16). Using young turkeys, we defined the replication, kinetics, and pathogenesis of Astrovirus infection. We demonstrated that Astrovirus replicated in the intestines with viral titers peaking between days 3 and 5 and dissipating by day 9 postinoculation. Viral antigen was detected in nonintestinal tissues, and infectious virus was isolated from these tissues and blood, primarily between 3 to 5 days postinfection (dpi), indicating viral spread was systemic, although viral replication was only detected in the intestine (3, 14). In these studies, we examined the role of the adaptive and innate immune responses in the control and clearance of Astrovirus infection using the turkey model. Our results demonstrated that T-cell populations and virus-specific antibodies (Abs) were not substantially altered in response to TAstV-2 infection. However, virus infection induced macrophage (Mφ) production of nitric oxide (NO), and NO suppressed viral replication during infection. This is the first experimental evidence of an interaction between Astrovirus and Mφs and demonstrates a potentially significant role for innate immunity in primary Astrovirus infection.
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Development of an RT-PCR diagnostic test for an avian Astrovirus.
Journal of virological methods, 2000Co-Authors: Matthew D. Koci, Bruce S. Seal, Stacey Schultz-cherryAbstract:Astroviruses are small round viruses that cause enteric disease in the young of several species. Detection and diagnosis of Astrovirus infection in non-human hosts relies heavily on electron microscopy and fluorescent antibody tests. Recently, our laboratory isolated and sequenced an avian Astrovirus from poult enteritis mortality syndrome affected turkeys. These studies describe the development of RT-PCR methods, which specifically detect regions of the viral capsid and polymerase genes, and demonstrate their use in detecting Astrovirus infection in commercial turkey flocks.
Shauna A. Marvin - One of the best experts on this subject based on the ideXlab platform.
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The Immune Response to Astrovirus Infection
Viruses, 2016Co-Authors: Shauna A. MarvinAbstract:Astroviruses are one of the leading causes of pediatric gastroenteritis worldwide and are clinically importantly pathogens in the elderly and immunocompromised populations. Although the use of cell culture systems and small animal models have enhanced our understanding of Astrovirus infection and pathogenesis, little is known about the immune response to Astrovirus infection. Studies from humans and animals suggest that adaptive immunity is important in restricting classic and novel Astrovirus infections, while studies from animal models and cell culture systems suggest that an innate immune system plays a role in limiting Astrovirus replication. The relative contribution of each arm of the immune system in restricting Astrovirus infection remains unknown. This review summarizes our current understanding of the immune response to Astrovirus infection and highlights some of the key questions that stem from these studies. A full understanding of the immune response to Astrovirus infection is required to be able to treat and control Astrovirus-induced gastroenteritis.
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oral administration of Astrovirus capsid protein is sufficient to induce acute diarrhea in vivo
Mbio, 2016Co-Authors: Victoria A Meliopoulos, Pamela Freiden, Shauna A. Marvin, Prashant K. Nighot, Rizwana Ali, Anthony T. Blikslager, Lindsey A. Moser, Muralidhar Reddivari, Richard J. Heath, Matthew D. KociAbstract:ABSTRACT The disease mechanisms associated with the onset of Astrovirus diarrhea are unknown. Unlike other enteric virus infections, Astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human Astrovirus serotype 1 (HAstV-1) capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey Astrovirus 2 (TAstV-2) capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, Astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the Astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction. IMPORTANCE Acute gastroenteritis, with its sequela diarrhea, is one of the most important causes of childhood morbidity and mortality worldwide. A variety of infectious agents cause gastroenteritis, and in many cases, an enterotoxin produced by the agent is involved in disease manifestations. Although we commonly think of bacteria as a source of toxins, at least one enteric virus, rotavirus, produces a protein with enterotoxigenic activity during viral replication. In these studies, we demonstrate that oral administration of the turkey Astrovirus 2 (TAstV-2) structural (capsid) protein induces acute diarrhea, increases barrier permeability, and causes relocalization of NHE3 in the small intestine, suggesting that rotavirus may not be alone in possessing enterotoxigenic activity.
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Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea In Vivo
American Society for Microbiology, 2016Co-Authors: Victoria A Meliopoulos, Pamela Freiden, Shauna A. Marvin, Prashant K. Nighot, Rizwana Ali, Anthony T. Blikslager, Lindsey A. Moser, Muralidhar Reddivari, Richard J. Heath, Matthew D. KociAbstract:The disease mechanisms associated with the onset of Astrovirus diarrhea are unknown. Unlike other enteric virus infections, Astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human Astrovirus serotype 1 (HAstV-1) capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey Astrovirus 2 (TAstV-2) capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, Astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the Astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction
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Type I Interferon Response Limits Astrovirus Replication and Protects Against Increased Barrier Permeability in vitro and in vivo
Journal of virology, 2015Co-Authors: Shauna A. Marvin, Troy Cline, Pamela Freiden, C. Theodore Huerta, Bridgett Sharp, Stacey Schultz-cherryAbstract:ABSTRACT Little 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 results in vivo using a murine Astrovirus (MuAstV) model, providing new evidence that virus-induced type I IFNs may protect against Astrovirus replication and pathogenesis in vivo . IMPORTANCE Human 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 both in vitro and in vivo . Importantly, we characterized a new mouse model for studying Astrovirus replication and pathogenesis.
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Crystal Structure of the Avian Astrovirus Capsid Spike
Journal of virology, 2013Co-Authors: Rebecca M. Dubois, Pamela Freiden, Shauna A. Marvin, Muralidhar Reddivari, Richard J. Heath, S.w. White, Stacey Schultz-cherryAbstract:Astroviruses are small, nonenveloped, single-stranded RNA viruses that cause diarrhea in a wide variety of mammals and birds. On the surface of the viral capsid are globular spikes that are thought to be involved in attachment to host cells. To understand the basis of species specificity, we investigated the structure of an avian Astrovirus capsid spike and compared it to a previously reported human Astrovirus capsid spike structure. Here we report the crystal structure of the turkey Astrovirus 2 (TAstV-2) capsid surface spike domain, determined to 1.5-A resolution, and identify three conserved patches on the surface of the spike that are candidate avian receptor-binding sites. Surprisingly, the overall TAstV-2 capsid spike structure is unique, with only distant structural similarities to the human Astrovirus capsid spike and other viral capsid spikes. There is an absence of conserved putative receptor-binding sites between the human and avian spikes. However, there is evidence for carbohydrate-binding sites in both human and avian spikes, and studies with human Astrovirus 1 (HAstV-1) suggest a minor role in infection for chondroitin sulfate but not heparin. Overall, our structural and functional studies provide new insights into Astrovirus host cell entry, species specificity, and evolution.
Stephan S Monroe - One of the best experts on this subject based on the ideXlab platform.
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Complete Genome Sequences of Human Astrovirus Prototype Strains (Types 1 to 8).
Microbiology resource announcements, 2019Co-Authors: Christina J. Castro, Stephan S Monroe, Emily Reynolds, Rachel L. Marine, Jan VinjéAbstract:We report the complete genome sequences of the eight human Astrovirus Oxford prototype strains. These sequences share 94.9% to 99.9% nucleotide identity with open reading frame 2 (ORF2) genes of Astrovirus genomes previously deposited in GenBank and include the first complete genome of human Astrovirus type 7.
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Gastroenteritis Viruses: Novartis Foundation Symposium 238 - Molecular Epidemiology of Human Astroviruses
Novartis Foundation symposium, 2008Co-Authors: Stephan S Monroe, Jennifer L. Holmes, Gaël BelliotAbstract:Publisher Summary Astroviruses were first detected by electron microscopy and the original assays for typing human Astrovirus strains employed time-consuming immune electron microscopy or cell-culture neutralization tests. The development of enzyme immunoassays for detecting human Astroviruses greatly simplified the characterization of strains and provided confirmation of the earlier studies indicating that serotype 1 (HAstV-1) is most common, accounting for over half of all strains detected. The further development of reverse transcription-polymerase chain reaction (RT-PCR) assays for detecting human Astroviruses allowed for more detailed characterization of Astrovirus strains by analysis of nucleotide sequence information. The increasing application of genetic comparisons for the characterization of Astrovirus strains has provided interesting molecular insights into the epidemiology of Astrovirus infection. The recent application of molecular diagnostic assays has firmly established that Astroviruses are associated with 5 to 8% of acute gastroenteritis in young children. It is not yet clear to what extent heterotypic protection is induced by a primary Astrovirus infection. Continued monitoring of Astrovirus strains will be useful to detect regional shifts in the predominant genotypes in circulation or the emergence of new genotypes.
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a prospective case control study of the role of Astrovirus in acute diarrhea among hospitalized young children
The Journal of Infectious Diseases, 2001Co-Authors: Penelope H Dennehy, Stephan S Monroe, Jacqueline S. Noel, Sara M Nelson, Sara Spangenberger, Roger I GlassAbstract:This study examines the importance of Astroviruses as a cause of acute diarrhea in hospitalized children <10 years old during a 5-year period. Stools were screened by electron microscopy and were tested for Astrovirus, rotavirus, and enteric adenovirus by EIA. During the study, 14.6% of hospitalized children had diarrhea. Astroviruses were second only to rotaviruses as etiologic agents of both community-acquired and nosocomial diarrhea. Community-acquired Astrovirus infection occurred in 6.8% of patients, and nosocomial disease occurred in 16.2%. Most cases occurred from March through June, and Astrovirus type 1 was the most common. The symptoms of Astrovirus-infected children were similar to those of children with rotavirus infection. However, Astrovirus-infected children had a lower median age, less dehydration, and lower symptom severity scores and were less likely to have been admitted for gastroenteritis than were children with rotavirus. Astrovirus, for which only rehydration therapy is required, should be considered as another common diarrheal pathogen in children <2 years old.
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Astrovirus diarrhea in egyptian children
The Journal of Infectious Diseases, 2000Co-Authors: Abdollah Naficy, Stephan S Monroe, Jennifer L. Holmes, Roger I Glass, Malla R Rao, Remon Abuelyazeed, Stephen J Savarino, Thomas F Wierzba, Robert W Frenck, John D ClemensAbstract:This study describes the epidemiology of Astrovirus diarrhea among a population-based cohort of 397 children aged <3 years residing in rural Egypt from 1995 to 1998. The age-specific incidence rates of Astrovirus diarrheal episodes per person-year were 0.38 for infants aged <6 months, 0.40 for those aged 6-11 months, 0.16 for those aged 12-23 months, and 0.05 for those aged 24-35 months. The overall incidence rate of Astrovirus diarrhea was the same as that of rotavirus diarrhea, 0.19 episodes per person-year. Astrovirus infection was pathogenic and associated with severe dehydration in 17% of the cases. The most frequent serotype was HAstV-1, and, in order of decreasing frequency, HAstV-5, HAstV-8 and HAstV-3, HAstV-6, HAstV-4, and HAstV-2. In determining whether Astrovirus diarrhea was associated with a reduced incidence of subsequent disease, there was evidence to suggest HAstV-1 homotypic immunity but not heterotypic immunity. Because we observed 38% of the incidence of Astrovirus diarrhea to occur in infants aged <6 months, a candidate Astrovirus vaccine would have to confer immunity very early in life.
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molecular epidemiology of childhood Astrovirus infection in child care centers
The Journal of Infectious Diseases, 1999Co-Authors: Douglas K Mitchell, David O Matson, Xi Jiang, Tamas Berke, Stephan S Monroe, Michael J Carter, Margaret M Willcocks, Larry K PickeringAbstract:This study assessed the role of human Astrovirus (HAstV) in outbreaks and sporadic cases of diarrhea among children attending child care centers (CCCs) and determined the infecting Astrovirus antigenic types by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequence analysis. Eight Astrovirus outbreaks occurred in 6 CCCs. Of 179 children with diarrhea, 36 (20%) had Astrovirus-associated diarrhea. Diarrhea stools obtained during diarrhea outbreaks were more likely to contain Astrovirus (40/476) than were samples not associated with a diarrhea outbreak (14/452) (P<.001). Type-specific RT-PCR and DNA sequencing identified 5 outbreaks associated with HAstV-1 and 3 outbreaks with HAstV-2. Sequential outbreaks in 2 CCCs occurred with a different type in the same year. Phylogenetic analysis identified 6 clades of HAstV-1 and 2 clades of HAstV-2 during this 1-year surveillance. Astrovirus was a significant cause of diarrhea outbreaks, and 2 antigenic types were present in the community during 1 diarrhea season.
Lindsey A. Moser - One of the best experts on this subject based on the ideXlab platform.
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oral administration of Astrovirus capsid protein is sufficient to induce acute diarrhea in vivo
Mbio, 2016Co-Authors: Victoria A Meliopoulos, Pamela Freiden, Shauna A. Marvin, Prashant K. Nighot, Rizwana Ali, Anthony T. Blikslager, Lindsey A. Moser, Muralidhar Reddivari, Richard J. Heath, Matthew D. KociAbstract:ABSTRACT The disease mechanisms associated with the onset of Astrovirus diarrhea are unknown. Unlike other enteric virus infections, Astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human Astrovirus serotype 1 (HAstV-1) capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey Astrovirus 2 (TAstV-2) capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, Astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the Astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction. IMPORTANCE Acute gastroenteritis, with its sequela diarrhea, is one of the most important causes of childhood morbidity and mortality worldwide. A variety of infectious agents cause gastroenteritis, and in many cases, an enterotoxin produced by the agent is involved in disease manifestations. Although we commonly think of bacteria as a source of toxins, at least one enteric virus, rotavirus, produces a protein with enterotoxigenic activity during viral replication. In these studies, we demonstrate that oral administration of the turkey Astrovirus 2 (TAstV-2) structural (capsid) protein induces acute diarrhea, increases barrier permeability, and causes relocalization of NHE3 in the small intestine, suggesting that rotavirus may not be alone in possessing enterotoxigenic activity.
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Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea In Vivo
American Society for Microbiology, 2016Co-Authors: Victoria A Meliopoulos, Pamela Freiden, Shauna A. Marvin, Prashant K. Nighot, Rizwana Ali, Anthony T. Blikslager, Lindsey A. Moser, Muralidhar Reddivari, Richard J. Heath, Matthew D. KociAbstract:The disease mechanisms associated with the onset of Astrovirus diarrhea are unknown. Unlike other enteric virus infections, Astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human Astrovirus serotype 1 (HAstV-1) capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey Astrovirus 2 (TAstV-2) capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, Astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the Astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction
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Astrovirus Increases Epithelial Barrier Permeability Independently of Viral Replication
Journal of virology, 2007Co-Authors: Lindsey A. Moser, Michael J Carter, Stacey Schultz-cherryAbstract: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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Pathogenesis of Astrovirus infection.
Viral immunology, 2005Co-Authors: Lindsey A. Moser, Stacey Schultz-cherryAbstract:Astroviruses are one of the leading causes of diarrhea worldwide. In spite of its impact on human health, little is known about Astrovirus pathogenesis. One reason for this may be the lack of a suitable small animal model for infection. In recent years, there has been increasing information on the mechanism of Astrovirus-induced disease in mammals (including humans) and birds. This review summarizes our current state of knowledge on Astrovirus pathogenesis.
