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Herpes Simplex Virus type 1 infection disrupts the ATR‐mediated damage response
Author(s) -
Mohni Kareem N,
Weller Sandra K
Publication year - 2010
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.24.1_supplement.492.12
Subject(s) - herpes simplex virus , dna damage , viral replication , biology , virology , virus , immunofluorescence , dna replication , phosphorylation , microbiology and biotechnology , dna , antibody , immunology , genetics
Herpes Simplex Virus type 1 (HSV‐1) is a large DNA virus that replicates in the nucleus of the host cell. HSV‐1 infection results in the activation of the ATM mediated damage response but not ATR. Since activation of ATM in uninfected cells generally results in the activation of ATR, we undertook the current study to determine how HSV‐1 infection disrupts the ATR mediated damage response. Preliminary data using phospho‐specific antibodies indicate that RPA and Chk1, which usually are targets of ATR, are not phosphorylated in infected cells. Using immunofluorescence we have shown that RPA and ATRIP are localized to the sites of viral DNA replication and that ATR and ATRIP do not colocalize in infected cells like they do during a normal damage response. We next wanted to see if we could activate the ATR pathway in infected cells by using hydroxyurea (HU). HU is a potent inhibitor of both cellular and viral DNA replication and will result in stalled replication forks and phosphorylation of the ATR substrate Chk1 in uninfected cells. Consistent with our previous data, Chk1 is not phosphorylated in response to HU in HSV‐1 infected cells. Taken together these results indicate that components of the ATR signaling pathway are present in viral replication compartments but that ATR signaling itself is disabled, perhaps by uncoupling ATR from ATRIP. This work was supported by Public Health Service grants AI21747 and AI69136.