Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.

Gamma-herpesviruses (gammaHVs) 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 gamma-herpesvirus 68 (gammaHV68) is the...

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Autores principales:	Xiaofei E, Seungmin Hwang, Soohwan Oh, Jong-Soo Lee, Joseph H Jeong, Yousang Gwack, Timothy F Kowalik, Ren Sun, Jae U Jung, Chengyu Liang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7127a9b72e3f4e9e863ffe49f934df6c
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spelling	oai:doaj.org-article:7127a9b72e3f4e9e863ffe49f934df6c2021-11-25T05:47:34ZViral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.1553-73661553-737410.1371/journal.ppat.1000609https://doaj.org/article/7127a9b72e3f4e9e863ffe49f934df6c2009-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19816569/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Gamma-herpesviruses (gammaHVs) 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 gamma-herpesvirus 68 (gammaHV68) 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 gammaHV68 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 gammaHVs confer persistent infections, further underscoring the importance of autophagy as a critical host determinant in the in vivo latency of gamma-herpesviruses.Xiaofei ESeungmin HwangSoohwan OhJong-Soo LeeJoseph H JeongYousang GwackTimothy F KowalikRen SunJae U JungChengyu LiangPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 10, p e1000609 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Xiaofei E Seungmin Hwang Soohwan Oh Jong-Soo Lee Joseph H Jeong Yousang Gwack Timothy F Kowalik Ren Sun Jae U Jung Chengyu Liang Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.
description	Gamma-herpesviruses (gammaHVs) 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 gamma-herpesvirus 68 (gammaHV68) 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 gammaHV68 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 gammaHVs confer persistent infections, further underscoring the importance of autophagy as a critical host determinant in the in vivo latency of gamma-herpesviruses.
format	article
author	Xiaofei E Seungmin Hwang Soohwan Oh Jong-Soo Lee Joseph H Jeong Yousang Gwack Timothy F Kowalik Ren Sun Jae U Jung Chengyu Liang
author_facet	Xiaofei E Seungmin Hwang Soohwan Oh Jong-Soo Lee Joseph H Jeong Yousang Gwack Timothy F Kowalik Ren Sun Jae U Jung Chengyu Liang
author_sort	Xiaofei E
title	Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.
title_short	Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.
title_full	Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.
title_fullStr	Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.
title_full_unstemmed	Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.
title_sort	viral bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/7127a9b72e3f4e9e863ffe49f934df6c
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Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.

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