GSBS Student Publications
Title
Deregulation of DNA damage signal transduction by herpesvirus latency-associated M2
GSBS Program
Biochemistry & Molecular Pharmacology
Publication Date
2006-05-30
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Microbiology and Molecular Genetics
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
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.
DOI of Published Version
10.1128/JVI.02732-05
Source
J Virol. 2006 Jun;80(12):5862-74. Link to article on publisher's site
Journal/Book/Conference Title
Journal of virology
Related Resources
PubMed ID
16731925
Repository Citation
Liang, Xiaozhen; Pickering, Mary Theresa; Cho, Nam-Hyuk; Chang, Heesoon; Volkert, Michael R.; Kowalik, Timothy F.; and Jung, Jae U., "Deregulation of DNA damage signal transduction by herpesvirus latency-associated M2" (2006). GSBS Student Publications. 697.
https://escholarship.umassmed.edu/gsbs_sp/697