Reovirus Cell Entry Requires Functional Microtubules

ABSTRACT Mammalian reovirus binds to cell-surface glycans and junctional adhesion molecule A and enters cells by receptor-mediated endocytosis in a process dependent on β1 integrin. Within the endocytic compartment, reovirus undergoes stepwise disassembly, allowing release of the transcriptionally a...

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Autores principales:	Bernardo A. Mainou, Paula F. Zamora, Alison W. Ashbrook, Daniel C. Dorset, 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/fcb6a766d1e8481da6e91b2e6eab5671
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spelling	oai:doaj.org-article:fcb6a766d1e8481da6e91b2e6eab56712021-11-15T15:43:09ZReovirus Cell Entry Requires Functional Microtubules10.1128/mBio.00405-132150-7511https://doaj.org/article/fcb6a766d1e8481da6e91b2e6eab56712013-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00405-13https://doaj.org/toc/2150-7511ABSTRACT Mammalian reovirus binds to cell-surface glycans and junctional adhesion molecule A and enters cells by receptor-mediated endocytosis in a process dependent on β1 integrin. Within the endocytic compartment, reovirus undergoes stepwise disassembly, allowing release of the transcriptionally active viral core into the cytoplasm. To identify cellular mediators of reovirus infectivity, we screened a library of small-molecule inhibitors for the capacity to block virus-induced cytotoxicity. In this screen, reovirus-induced cell killing was dampened by several compounds known to impair microtubule dynamics. Microtubule inhibitors were assessed for blockade of various stages of the reovirus life cycle. While these drugs did not alter reovirus cell attachment or internalization, microtubule inhibitors diminished viral disassembly kinetics with a concomitant decrease in infectivity. Reovirus virions colocalize with microtubules and microtubule motor dynein 1 during cell entry, and depolymerization of microtubules results in intracellular aggregation of viral particles. These data indicate that functional microtubules are required for proper sorting of reovirus virions following internalization and point to a new drug target for pathogens that use the endocytic pathway to invade host cells. IMPORTANCE Screening libraries of well-characterized drugs for antiviral activity enables the rapid characterization of host processes required for viral infectivity and provides new therapeutic applications for established pharmaceuticals. Our finding that microtubule-inhibiting drugs impair reovirus infection identifies a new cell-based antiviral target.Bernardo A. MainouPaula F. ZamoraAlison W. AshbrookDaniel C. DorsetKwang S. KimTerence S. DermodyAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 4 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Bernardo A. Mainou Paula F. Zamora Alison W. Ashbrook Daniel C. Dorset Kwang S. Kim Terence S. Dermody Reovirus Cell Entry Requires Functional Microtubules
description	ABSTRACT Mammalian reovirus binds to cell-surface glycans and junctional adhesion molecule A and enters cells by receptor-mediated endocytosis in a process dependent on β1 integrin. Within the endocytic compartment, reovirus undergoes stepwise disassembly, allowing release of the transcriptionally active viral core into the cytoplasm. To identify cellular mediators of reovirus infectivity, we screened a library of small-molecule inhibitors for the capacity to block virus-induced cytotoxicity. In this screen, reovirus-induced cell killing was dampened by several compounds known to impair microtubule dynamics. Microtubule inhibitors were assessed for blockade of various stages of the reovirus life cycle. While these drugs did not alter reovirus cell attachment or internalization, microtubule inhibitors diminished viral disassembly kinetics with a concomitant decrease in infectivity. Reovirus virions colocalize with microtubules and microtubule motor dynein 1 during cell entry, and depolymerization of microtubules results in intracellular aggregation of viral particles. These data indicate that functional microtubules are required for proper sorting of reovirus virions following internalization and point to a new drug target for pathogens that use the endocytic pathway to invade host cells. IMPORTANCE Screening libraries of well-characterized drugs for antiviral activity enables the rapid characterization of host processes required for viral infectivity and provides new therapeutic applications for established pharmaceuticals. Our finding that microtubule-inhibiting drugs impair reovirus infection identifies a new cell-based antiviral target.
format	article
author	Bernardo A. Mainou Paula F. Zamora Alison W. Ashbrook Daniel C. Dorset Kwang S. Kim Terence S. Dermody
author_facet	Bernardo A. Mainou Paula F. Zamora Alison W. Ashbrook Daniel C. Dorset Kwang S. Kim Terence S. Dermody
author_sort	Bernardo A. Mainou
title	Reovirus Cell Entry Requires Functional Microtubules
title_short	Reovirus Cell Entry Requires Functional Microtubules
title_full	Reovirus Cell Entry Requires Functional Microtubules
title_fullStr	Reovirus Cell Entry Requires Functional Microtubules
title_full_unstemmed	Reovirus Cell Entry Requires Functional Microtubules
title_sort	reovirus cell entry requires functional microtubules
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/fcb6a766d1e8481da6e91b2e6eab5671
work_keys_str_mv	AT bernardoamainou reoviruscellentryrequiresfunctionalmicrotubules AT paulafzamora reoviruscellentryrequiresfunctionalmicrotubules AT alisonwashbrook reoviruscellentryrequiresfunctionalmicrotubules AT danielcdorset reoviruscellentryrequiresfunctionalmicrotubules AT kwangskim reoviruscellentryrequiresfunctionalmicrotubules AT terencesdermody reoviruscellentryrequiresfunctionalmicrotubules
_version_	1718427622198738944

Reovirus Cell Entry Requires Functional Microtubules

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