Efficient herpes simplex virus 1 replication requires cellular ATR pathway proteins

Kareem N. Mohni, Alexander R. Dee, Samantha Smith, April J. Schumacher, Sandra K. Weller

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Herpes simplex virus 1 (HSV-1) is a double-stranded DNA virus that replicates in the nucleus of the host cell and is known to interact with several components of the cellular DNA-damage-signaling machinery. We have previously reported that the DNAdamage response kinase, ATR, is specifically inactivated in HSV-1-infected cells. On the other hand, we have also shown that ATR and its scaffolding protein, ATRIP, are recruited to viral replication compartments, where they play beneficial roles during HSV-1 replication. In order to better understand this apparent discrepancy, we tested the hypothesis that some of the components of the ATR pathway may exert an antiviral effect on infection. In fact, we learned that all 10 of the canonical ATR pathwayproteins are stable in HSV-infected cells and are recruited to viral replication compartments; furthermore, short hairpin RNA (shRNA) knockdown shows that several, including ATRIP, RPA70, TopBP1, Claspin, and CINP, are required for efficient HSV-1 replication. We also determined that activation of the ATR kinase prior to infection did not affect virus yield but did resultinreduced levels of recombination between coinfecting viruses. Together, these data suggest that ATR pathway proteins are notantiviral per se but that activation of ATR signaling may have negative consequences during viral replication, such as inhibitingrecombination.

Original languageEnglish (US)
Pages (from-to)531-542
Number of pages12
JournalJournal of virology
Volume87
Issue number1
DOIs
StatePublished - Jan 2013

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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