Viral Bcl-2-Mediated Evasion of Autophagy Aids Chronic Infection of γHerpesvirus 68

Viral Bcl-2-Mediated Evasion of Autophagy Aids Chronic Infection of γHerpesvirus 68

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Viral Bcl-2-Mediated Evasion of Autophagy Aids Chronic Infection of γHerpesvirus 68

dc.contributor.author	E, Xiaofei
dc.contributor.author	Hwang, Seungmin
dc.contributor.author	Oh, Soohwan
dc.contributor.author	Lee, Jong-Soo
dc.contributor.author	Jeong, Joseph H.
dc.contributor.author	Gwack, Yousang
dc.contributor.author	Kowalik, Timothy F.
dc.contributor.author	Sun, Ren
dc.contributor.author	Liang, Chengyu
dc.contributor.author	Stevenson, Philip G.
dc.contributor.author	Jung, Jae Ung
dc.date.accessioned	2011-05-08T00:16:55Z
dc.date.issued	2009
dc.identifier.citation	E, Xiaofei, Seungmin Hwang, Soohwan Oh, Jong-Soo Lee, Joseph H. Jeong, Yousang Gwack, Timothy F. Kowalik, Ren Sun, Jae U. Jung, and Chengyu Liang. 2009. Viral Bcl-2-mediated evasion of autophagy aids chronic infection of γHerpesvirus 68. PLoS Pathogens 5(10).	en_US
dc.identifier.issn	1553-7366	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:4882983
dc.description.abstract	γ-herpesviruses (γHVs) have developed an interaction with their hosts wherein they establish a life-long persistent infection and are associated with the onset of various malignancies. One critical virulence factor involved in the persistency of murine γ-herpesvirus 68 (γHV68) is the viral homolog of the Bcl-2 protein (vBcl-2), which has been implicated to counteract both host apoptotic responses and autophagy pathway. However, the relative significance of the two activities of vBcl-2 in viral persistent infection has yet to be elucidated. Here, by characterizing a series of loss-of-function mutants of vBcl-2, we have distinguished the vBcl-2-mediated antagonism of autophagy from the vBcl-2-mediated inhibition of apoptosis in vitro and in vivo. A mutant γHV68 virus lacking the anti-autophagic activity of vBcl-2 demonstrates an impaired ability to maintain chronic infections in mice, whereas a mutant virus lacking the anti-apoptotic activity of vBcl-2 establishes chronic infections as efficiently as the wild-type virus but displays a compromised ability for ex vivo reactivation. Thus, the vBcl-2-mediated antagonism of host autophagy constitutes a novel mechanism by which γHVs confer persistent infections, further underscoring the importance of autophagy as a critical host determinant in the in vivo latency of γ-herpesviruses.	en_US
dc.language.iso	en_US	en_US
dc.publisher	Public Library of Science	en_US
dc.relation.isversionof	doi://10.1371/journal.ppat.1000609	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752191/pdf/	en_US
dash.license	LAA
dc.subject	cell biology	en_US
dc.subject	microbiology	en_US
dc.subject	molecular biology	en_US
dc.subject	virology	en_US
dc.title	Viral Bcl-2-Mediated Evasion of Autophagy Aids Chronic Infection of γHerpesvirus 68	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	PLoS Pathogens	en_US
dash.depositing.author	Jung, Jae Ung
dc.date.available	2011-05-08T00:16:55Z
dash.affiliation.other	HMS^Microbiology and Molecular Genetics	en_US