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

Overview of attention for article published in Virology Journal, January 2016
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Title
H2AX phosphorylation and DNA damage kinase activity are dispensable for herpes simplex virus replication
Published in
Virology Journal, January 2016
DOI 10.1186/s12985-016-0470-1
Pubmed ID
Authors

Carolyn Botting, Xu Lu, Steven 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 inhibition of ATM in oral keratinocytes or following infection of ATM(-/-) cells. Inhibition of the closely related kinase ATR (whether by chemical inhibitor or siRNA disruption) had no effect on H2AX phosphorylation and reduced viral DNA replication only moderately. During infection by HSV-2, H2AX phosphorylation was similarly dispensable but was dependent on both ATM activity and viral DNA replication. H2AX phosphorylation represents a cell type-specific and virus type-specific host response to HSV infection with little impact on viral infection.

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The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 27 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 6 22%
Student > Ph. D. Student 5 19%
Student > Master 3 11%
Student > Doctoral Student 3 11%
Other 1 4%
Other 2 7%
Unknown 7 26%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 30%
Biochemistry, Genetics and Molecular Biology 7 26%
Immunology and Microbiology 2 7%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Psychology 1 4%
Other 1 4%
Unknown 7 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 January 2016.
All research outputs
#18,437,241
of 22,842,950 outputs
Outputs from Virology Journal
#2,441
of 3,046 outputs
Outputs of similar age
#287,100
of 396,850 outputs
Outputs of similar age from Virology Journal
#38
of 43 outputs
Altmetric has tracked 22,842,950 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
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