Document Detail


Subversion of autophagy by Kaposi's sarcoma-associated herpesvirus impairs oncogene-induced senescence.
MedLine Citation:
PMID:  22341465     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute oncogenic stress can activate autophagy and facilitate permanent arrest of the cell cycle through a failsafe mechanism known as oncogene-induced senescence (OIS). Kaposi's sarcoma-associated herpesvirus (KSHV) proteins are known to subvert autophagic pathways, but the link to Kaposi's sarcoma pathogenesis is unclear. We find that oncogenic assault caused by latent KSHV infection elicits DNA damage responses (DDRs) characteristic of OIS, yet infected cells display only modest levels of autophagy and fail to senesce. These aberrant responses result from the combined activities of tandemly expressed KSHV v-cyclin and v-FLIP proteins. v-Cyclin deregulates the cell cycle, triggers DDRs, and if left unchecked can promote autophagy and senescence. However, during latency v-FLIP blocks v-cyclin-induced autophagy and senescence in a manner that requires intact v-FLIP ATG3-binding domains. Together, these data reveal a coordinated viral gene expression program that usurps autophagy, blocks senescence, and facilitates the proliferation of KSHV-infected cells.
Authors:
Andrew M Leidal; David P Cyr; Richard J Hill; Patrick W K Lee; Craig McCormick
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell host & microbe     Volume:  11     ISSN:  1934-6069     ISO Abbreviation:  Cell Host Microbe     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-06-06     Revised Date:  2013-04-04    
Medline Journal Info:
Nlm Unique ID:  101302316     Medline TA:  Cell Host Microbe     Country:  United States    
Other Details:
Languages:  eng     Pagination:  167-80     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, Nova Scotia B3H 4R2, Canada.
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MeSH Terms
Descriptor/Qualifier:
Aging*
Autophagy*
DNA Damage
DNA Repair
Herpesvirus 8, Human / immunology,  pathogenicity*
Host-Pathogen Interactions*
Immune Evasion*
Oncogene Proteins / metabolism*
Viral Proteins / metabolism
Virulence Factors / metabolism
Chemical
Reg. No./Substance:
0/Oncogene Proteins; 0/Viral Proteins; 0/Virulence Factors
Comments/Corrections
Comment In:
Autophagy. 2012 Jul 1;8(7):1138-40   [PMID:  22735194 ]
Cell Host Microbe. 2012 Feb 16;11(2):101-3   [PMID:  22341458 ]

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