Subversion of autophagy by Kaposi's sarcoma-associated herpesvirus impairs oncogene-induced senescence.
Cell Host Microbe
; 11(2): 167-80, 2012 Feb 16.
Article
em En
| MEDLINE
| ID: mdl-22341465
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Envelhecimento
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Proteínas Oncogênicas
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Herpesvirus Humano 8
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Interações Hospedeiro-Patógeno
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Evasão da Resposta Imune
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
Cell Host Microbe
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Canadá
País de publicação:
Estados Unidos