Directional Release of Reovirus from the Apical Surface of Polarized Endothelial Cells

ABSTRACT Bloodstream spread is a critical step in the pathogenesis of many viruses. However, mechanisms that promote viremia are not well understood. Reoviruses are neurotropic viruses that disseminate hematogenously to the central nervous system. Junctional adhesion molecule A (JAM-A) is a tight ju...

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Autores principales:	Caroline M. Lai, Bernardo A. Mainou, Kwang S. Kim, Terence S. Dermody
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2e67d0cca00c499189608a74b88c4714
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spelling	oai:doaj.org-article:2e67d0cca00c499189608a74b88c47142021-11-15T15:40:28ZDirectional Release of Reovirus from the Apical Surface of Polarized Endothelial Cells10.1128/mBio.00049-132150-7511https://doaj.org/article/2e67d0cca00c499189608a74b88c47142013-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00049-13https://doaj.org/toc/2150-7511ABSTRACT Bloodstream spread is a critical step in the pathogenesis of many viruses. However, mechanisms that promote viremia are not well understood. Reoviruses are neurotropic viruses that disseminate hematogenously to the central nervous system. Junctional adhesion molecule A (JAM-A) is a tight junction protein that serves as a receptor for reovirus. JAM-A is required for establishment of viremia in infected newborn mice and viral spread to sites of secondary replication. To determine how viruses gain access to the circulatory system, we examined reovirus infection of polarized human brain microvascular endothelial cells (HBMECs). Reovirus productively infects polarized HBMECs, but infection does not alter tight junction integrity. Apical infection of polarized HBMECs is more efficient than basolateral infection, which is attributable to viral engagement of sialic acid and JAM-A. Viral release occurs exclusively from the apical surface via a mechanism that is not associated with lysis or apoptosis of infected cells. These data suggest that infection of endothelial cells routes reovirus apically into the bloodstream for systemic dissemination in the host. Understanding how viruses invade the bloodstream may aid in the development of therapeutics that block this step in viral pathogenesis. IMPORTANCE Bloodstream spread of viruses within infected hosts is a critical but poorly understood step in viral disease. Reoviruses first enter the host through the oral or respiratory route and infect cells in the central nervous system. Spread of reoviruses to the brain occurs by blood or nerves, which makes reoviruses useful models for studies of systemic viral dissemination. In this study, we examined how reoviruses infect endothelial cells, which form the walls of blood vessels. We found that reovirus infection of endothelial cells allows the virus to enter blood vessels and serves as a means for the virus to reach high titers in the circulation. Understanding how reovirus is routed through endothelial cells may aid in the design of antiviral drugs that target this important step in systemic viral infections.Caroline M. LaiBernardo A. MainouKwang S. KimTerence S. DermodyAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 2 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Caroline M. Lai Bernardo A. Mainou Kwang S. Kim Terence S. Dermody Directional Release of Reovirus from the Apical Surface of Polarized Endothelial Cells
description	ABSTRACT Bloodstream spread is a critical step in the pathogenesis of many viruses. However, mechanisms that promote viremia are not well understood. Reoviruses are neurotropic viruses that disseminate hematogenously to the central nervous system. Junctional adhesion molecule A (JAM-A) is a tight junction protein that serves as a receptor for reovirus. JAM-A is required for establishment of viremia in infected newborn mice and viral spread to sites of secondary replication. To determine how viruses gain access to the circulatory system, we examined reovirus infection of polarized human brain microvascular endothelial cells (HBMECs). Reovirus productively infects polarized HBMECs, but infection does not alter tight junction integrity. Apical infection of polarized HBMECs is more efficient than basolateral infection, which is attributable to viral engagement of sialic acid and JAM-A. Viral release occurs exclusively from the apical surface via a mechanism that is not associated with lysis or apoptosis of infected cells. These data suggest that infection of endothelial cells routes reovirus apically into the bloodstream for systemic dissemination in the host. Understanding how viruses invade the bloodstream may aid in the development of therapeutics that block this step in viral pathogenesis. IMPORTANCE Bloodstream spread of viruses within infected hosts is a critical but poorly understood step in viral disease. Reoviruses first enter the host through the oral or respiratory route and infect cells in the central nervous system. Spread of reoviruses to the brain occurs by blood or nerves, which makes reoviruses useful models for studies of systemic viral dissemination. In this study, we examined how reoviruses infect endothelial cells, which form the walls of blood vessels. We found that reovirus infection of endothelial cells allows the virus to enter blood vessels and serves as a means for the virus to reach high titers in the circulation. Understanding how reovirus is routed through endothelial cells may aid in the design of antiviral drugs that target this important step in systemic viral infections.
format	article
author	Caroline M. Lai Bernardo A. Mainou Kwang S. Kim Terence S. Dermody
author_facet	Caroline M. Lai Bernardo A. Mainou Kwang S. Kim Terence S. Dermody
author_sort	Caroline M. Lai
title	Directional Release of Reovirus from the Apical Surface of Polarized Endothelial Cells
title_short	Directional Release of Reovirus from the Apical Surface of Polarized Endothelial Cells
title_full	Directional Release of Reovirus from the Apical Surface of Polarized Endothelial Cells
title_fullStr	Directional Release of Reovirus from the Apical Surface of Polarized Endothelial Cells
title_full_unstemmed	Directional Release of Reovirus from the Apical Surface of Polarized Endothelial Cells
title_sort	directional release of reovirus from the apical surface of polarized endothelial cells
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/2e67d0cca00c499189608a74b88c4714
work_keys_str_mv	AT carolinemlai directionalreleaseofreovirusfromtheapicalsurfaceofpolarizedendothelialcells AT bernardoamainou directionalreleaseofreovirusfromtheapicalsurfaceofpolarizedendothelialcells AT kwangskim directionalreleaseofreovirusfromtheapicalsurfaceofpolarizedendothelialcells AT terencesdermody directionalreleaseofreovirusfromtheapicalsurfaceofpolarizedendothelialcells
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Directional Release of Reovirus from the Apical Surface of Polarized Endothelial Cells

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