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Efficient Replication of Herpes Simplex Virus Type 1 Involves DNA Damage Pathways (LB122)
Author(s) -
Botting Carolyn,
Lu Xu,
Triezenberg Steven
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb122
Subject(s) - herpes simplex virus , dna damage , kinase , dna replication , biology , phosphorylation , viral replication , ataxia telangiectasia , histone , virology , microbiology and biotechnology , virus , dna , genetics
Herpes simplex virus type 1 (HSV‐1) is a predominant cause of cold sores and is prevalent in 90% of the world’s population. While examining chromatin changes during HSV‐1 infection, we observed histone H2AX phosphorylation, a marker of DNA damage response activation. Since ataxia telangiectasia mutated (ATM) and ataxia telangiectasia Rad3 related (ATR) kinases are responsible for H2AX phosphorylation, we hypothesized that these kinases are involved in HSV‐1 replication. This hypothesis was supported by significant reduction in HSV‐1 replication upon addition of CGK733, an ATM and ATR inhibitor. Small molecule inhibitors specifically targeting either ATM or ATR affected replication only when used in combination, but not to the same extent as that of CGK733. Furthermore, shRNA and siRNAs targeting ATM or ATR caused only a modest reduction in HSV‐1 replication. Together these data suggest a redundant mechanism in which the ATM and ATR pathways may be used interchangeably to promote HSV‐1 replication. Thus new treatment for HSV‐1 could involve simultaneous inhibition of both these pathways.