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Gamma-herpesvirus kinase actively initiates a DNA damage response by inducing phosphorylation of H2AX to foster viral replication. Cell Host Microbe 2007 Jun 14;1(4):275-86

Date

11/17/2007

Pubmed ID

18005708

Pubmed Central ID

PMC2034359

DOI

10.1016/j.chom.2007.05.008

Scopus ID

2-s2.0-34249910944   105 Citations

Abstract

DNA virus infection can elicit the DNA damage response in host cells, including ATM kinase activation and H2AX phosphorylation. This is considered to be the host cell response to replicating viral DNA. In contrast, we show that during infection of macrophages murine gamma-herpesvirus 68 (gammaHV68) actively induces H2AX phosphorylation by expressing a viral kinase (orf36). GammaHV68-encoded orf36 kinase and its EBV homolog, BGLF4, induce H2AX phosphorylation independently of other viral genes. The process requires the kinase domain of Orf36 and is enhanced by ATM. Orf36 is important for gammaHV68 replication in infected animals, and orf36, H2AX, and ATM are all critical for efficient gammaHV68 replication in primary macrophages. Thus, activation of proximal components of the DNA damage signaling response is an active viral kinase-driven strategy required for efficient gamma-herpesvirus replication.

Author List

Tarakanova VL, Leung-Pineda V, Hwang S, Yang CW, Matatall K, Basson M, Sun R, Piwnica-Worms H, Sleckman BP, Virgin HW 4th

Author

Vera Tarakanova PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
DNA Damage
Gammaherpesvirinae
Herpesviridae Infections
Herpesvirus 4, Human
Histones
Humans
Open Reading Frames
Phosphoproteins
Phosphorylation
Plasmids
Protein Kinases
Viral Proteins
Virus Replication
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a