Subversion of autophagy by Kaposi's sarcoma-associated herpesvirus impairs oncogene-induced senescence

Andrew M. Leidal, David P. Cyr, Richard Hill, Patrick W. K. Lee, Craig Mccormick

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)167-180
Number of pages4
JournalCell Host & Microbe
Issue number2
Publication statusPublished - 15 Feb 2012
Externally publishedYes


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