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- Title
Viral Bcl-2-Mediated Evasion of Autophagy Aids Chronic Infection of γHerpesvirus 68.
- Authors
Xiaofei E; Seungmin Hwang; Soohwan Oh; Jong-Soo Lee; Jeong, Joseph H.; Yousang Gwack; Kowalik, Timothy F.; Ren Sun; Jung, Jae U.; Chengyu Liang
- 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 c-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 cHVs confer persistent infections, further underscoring the importance of autophagy as a critical host determinant in the in vivo latency of γ-herpesviruses.
- Subjects
HERPESVIRUS diseases; MORPHOLOGY; CHRONIC diseases; FLUOROSIS; ANTIBIOSIS
- Publication
PLoS Pathogens, 2009, Vol 5, Issue 10, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1000609