Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea <italic toggle="yes">In Vivo</italic>

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 astrov...

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Autores principales:	Victoria A. Meliopoulos, Shauna A. Marvin, Pamela Freiden, Lindsey A. Moser, Prashant Nighot, Rizwana Ali, Anthony Blikslager, Muralidhar Reddivari, Richard J. Heath, Matthew D. Koci, Stacey Schultz-Cherry
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/eea64f2f4c4548f188b74334aaaa9837
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spelling	oai:doaj.org-article:eea64f2f4c4548f188b74334aaaa98372021-11-15T15:50:16ZOral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea <italic toggle="yes">In Vivo</italic>10.1128/mBio.01494-162150-7511https://doaj.org/article/eea64f2f4c4548f188b74334aaaa98372016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01494-16https://doaj.org/toc/2150-7511ABSTRACT 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.Victoria A. MeliopoulosShauna A. MarvinPamela FreidenLindsey A. MoserPrashant NighotRizwana AliAnthony BlikslagerMuralidhar ReddivariRichard J. HeathMatthew D. KociStacey Schultz-CherryAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Victoria A. Meliopoulos Shauna A. Marvin Pamela Freiden Lindsey A. Moser Prashant Nighot Rizwana Ali Anthony Blikslager Muralidhar Reddivari Richard J. Heath Matthew D. Koci Stacey Schultz-Cherry Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea <italic toggle="yes">In Vivo</italic>
description	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.
format	article
author	Victoria A. Meliopoulos Shauna A. Marvin Pamela Freiden Lindsey A. Moser Prashant Nighot Rizwana Ali Anthony Blikslager Muralidhar Reddivari Richard J. Heath Matthew D. Koci Stacey Schultz-Cherry
author_facet	Victoria A. Meliopoulos Shauna A. Marvin Pamela Freiden Lindsey A. Moser Prashant Nighot Rizwana Ali Anthony Blikslager Muralidhar Reddivari Richard J. Heath Matthew D. Koci Stacey Schultz-Cherry
author_sort	Victoria A. Meliopoulos
title	Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea <italic toggle="yes">In Vivo</italic>
title_short	Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea <italic toggle="yes">In Vivo</italic>
title_full	Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea <italic toggle="yes">In Vivo</italic>
title_fullStr	Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea <italic toggle="yes">In Vivo</italic>
title_full_unstemmed	Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea <italic toggle="yes">In Vivo</italic>
title_sort	oral administration of astrovirus capsid protein is sufficient to induce acute diarrhea <italic toggle="yes">in vivo</italic>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/eea64f2f4c4548f188b74334aaaa9837
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Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea <italic toggle="yes">In Vivo</italic>

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