DNA repair proteins affect the lifecycle of herpes simplex virus 1.
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.
Lilley
Caroline E
CE
Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Carson
Christian T
CT
Muotri
Alysson R
AR
Gage
Fred H
FH
Weitzman
Matthew D
MD
D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology / Q000821:virology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014779:Virus Replication