H2AX phosphorylation and DNA damage kinase activity are dispensable for herpes simplex virus replication

Virology Journal
Carolyn BottingSteven J Triezenberg

Abstract

Herpes simplex virus type 1 (HSV-1) can establish both lytic and latent infections in humans. The phosphorylation of histone H2AX, a common marker of DNA damage, during lytic infection by HSV-1 is well established. However, the role(s) of H2AX phosphorylation in lytic infection remain unclear. Following infection of human foreskin fibroblasts by HSV-1 or HSV-2, we assayed the phosphorylation of H2AX in the presence of inhibitors of transcription, translation, or viral DNA replication, or in the presence of inhibitors of ATM and ATR kinases (KU-55933 and VE-821, respectively). We also assayed viral replication in fibroblasts in the presence of the kinase inhibitors or siRNAs specific for ATM and ATR, as well as in cell lines deficient for either ATR or ATM. The expression of viral immediate-early and early proteins (including the viral DNA polymerase), but not viral DNA replication or late protein expression, were required for H2AX phosphorylation following HSV-1 infection. Inhibition of ATM kinase activity prevented HSV-stimulated H2AX phosphorylation but had only a minor effect on DNA replication and virus yield in HFF cells. These results differ from previous reports of a dramatic reduction in viral yield following chemical i...Continue Reading

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Citations

Jul 12, 2018·Annual Review of Virology·Matthew D Weitzman, Amélie Fradet-Turcotte
Apr 3, 2020·Journal of Radiation Research·Qiuning ZhangXiaohu Wang
Mar 4, 2017·Advances in Virology·Jay C Brown

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Datasets Mentioned

BETA
GM01588A
GM02052F
GM18366D
GM05757B
GM02530

Methods Mentioned

BETA
PCR
transfections

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