Subversion of Autophagy by Kaposi's Sarcoma-Associated Herpesvirus Impairs Oncogene-Induced Senescence
Open accessAbstract
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.
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The functional relevance of autophagy in senescence varies depending on cell type and senescence triggers.
“Some studies have touched on the functional relevance of autophagy in senescence, where its role appears to vary depending on cell type and senescence triggers (Patschan et al. 2007; Young et al. 2009; Leidal et al. 2012; Mosieniak et al. 2012; Singh et al. 2012; Dörr et al. 2013).”
From Cellular senescence and its effector programs (2014) · cites this paper as Leidal et al. 2012
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BackgroundDRAM, a p53-Induced Modulator of Autophagy, Is Critical for Apoptosis
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“Cells subjected to serum and amino acid starvation activated autophagy (Figures S3A and S3B) but failed to upregulate DRAM, Sestrin1, or Sestrin2, indicating that upregulation of these genes is not a universal feature of autophagy, but instead may be limited to OIS.”
BackgroundInfluentialEndogenous MHC Class II Processing of a Viral Nuclear Antigen After Autophagy
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- Authors
- Leidal, A. M., Cyr, D. P., Hill, R. J., Lee, P. W. K., & McCormick, C.
- Affiliations
- Dalhousie University (CA)
- Corresponding author
- Lee, Patrick W.K.
- McCormick, Craig
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 11
- Issue
- 2
- Pages
- 167-180
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W2099782488
- Cited by
- 113
- References
- 13
- Citations by year
- 2025: 3 · 2024: 8 · 2023: 3 · 2022: 4 · 2021: 11 · 2020: 8 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 7 · 2015: 9 · 2014: 18 · 2013: 11 · 2012: 8
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-06-08)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Cancer Society
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- Kaposi's sarcoma-associated herpesvirus, oncogene-induced senescence, autophagy, ATG3, DNA damage response, viral latency, viral oncogenesis, cell cycle dysregulation
- MeSH terms
- Aging, Autophagy, DNA Damage, DNA Repair, Viral Proteins, Oncogene Proteins, Herpesvirus 8, Human, Virulence Factors, Host-Pathogen Interactions, Immune Evasion
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