DNA repair proteins affect the lifecycle of herpes simplex virus 1

doi:10.1073/pnas.0501916102

DNA repair proteins affect the lifecycle of herpes simplex virus 1

^*Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037; and ^†Department of Biology, University of California at San Diego, La Jolla, CA 92093

Communicated by Inder M. Verma, The Salk Institute for Biological Studies, La Jolla, CA, March 9, 2005 (received for review December 10, 2004)

Abstract

We report that herpes simplex virus 1 (HSV-1) infection can activate and exploit a cellular DNA damage response that aids viral replication in nonneuronal cells. Early in HSV-1 infection, several members of the cellular DNA damage-sensing machinery are activated and accumulate at sites of viral DNA replication. When this cellular response is abrogated, formation of HSV-1 replication centers is retarded, and viral production is compromised. In neurons, HSV-1 replication centers fail to mature, and the DNA damage response is not initiated. These data suggest that the failure of neurons to mount a DNA damage response to HSV-1 may contribute to the establishment of latency.

Footnotes

↵ ‡ To whom correspondence should be addressed at: The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037. E-mail: weitzman{at}salk.edu.
Author contributions: C.E.L. and M.D.W. designed research; C.E.L., C.T.C., and A.R.M. performed research; A.R.M. and F.H.G. contributed new reagents/analytic tools; C.E.L., F.H.G., and M.D.W. analyzed data; and C.E.L. and M.D.W. wrote the paper.
Abbreviations: HSV-1, herpes simplex virus 1; ATM, ataxia telangiectasia mutated; ATR, ATM-Rad3 related; DNA-PKcs, catalytic subunit of the DNA-dependent protein kinase; ICP, infected cell polypeptide; IE, immediate early; moi, multiplicity of infection; PAA, phosphonoacetic acid; hpi, h postinfection; A-TLD, ataxia telangiectasia-like disorder; A-T, ataxia telangiectasia.
Freely available online through the PNAS open access option.