Deregulation of DNA damage signal transduction by herpesvirus latency-associated M2
Authors
Liang, XiaozhenPickering, Mary Theresa
Cho, Nam-Hyuk
Chang, Heesoon
Volkert, Michael R.
Kowalik, Timothy F.
Jung, Jae U.
UMass Chan Affiliations
Department of Microbiology and Molecular GeneticsGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2006-05-30Keywords
Active Transport, Cell Nucleus; Animals; Apoptosis; Cell Cycle; Cell Line; *DNA Damage; DNA Repair; DNA-Binding Proteins; G1 Phase; Herpesviridae Infections; Humans; Mice; Rhadinovirus; *Signal Transduction; Tumor Virus Infections; Viral Matrix Proteins; *Virus LatencyLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Infected cells recognize viral replication as a DNA damage stress and elicit a DNA damage response that ultimately induces apoptosis as part of host immune surveillance. Here, we demonstrate a novel mechanism where the murine gamma herpesvirus 68 (gammaHV68) latency-associated, anti-interferon M2 protein inhibits DNA damage-induced apoptosis by interacting with the DDB1/COP9/cullin repair complex and the ATM DNA damage signal transducer. M2 expression constitutively induced DDB1 nuclear localization and ATM kinase activation in the absence of DNA damage. Activated ATM subsequently induced Chk activation and p53 phosphorylation and stabilization without eliciting H2AX phosphorylation and MRN recruitment to foci upon DNA damage. Consequently, M2 expression inhibited DNA repair, rendered cells resistant to DNA damage-induced apoptosis, and induced a G(1) cell cycle arrest. Our results suggest that gammaHV68 M2 blocks apoptosis-mediated intracellular innate immunity, which might ultimately contribute to its role in latent infection.Source
J Virol. 2006 Jun;80(12):5862-74. Link to article on publisher's siteDOI
10.1128/JVI.02732-05Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34047PubMed ID
16731925Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/JVI.02732-05