TY - JOUR
T1 - γ-Herpesvirus Kinase Actively Initiates a DNA Damage Response by Inducing Phosphorylation of H2AX to Foster Viral Replication
AU - Tarakanova, Vera L.
AU - Leung-Pineda, Van
AU - Hwang, Seungmin
AU - Yang, Chiao Wen
AU - Matatall, Katie
AU - Basson, Mickael
AU - Sun, Ren
AU - Piwnica-Worms, Helen
AU - Sleckman, Barry P.
AU - Virgin IV, Herbert W.
N1 - Funding Information:
We thank Darren Kreamalmayer for his outstanding expertise in animal breeding and members of the Virgin and Sleckman laboratories for helpful discussions. Dr. Lynda Morrison provided valuable reagents. Dr. Robert Schreiber supplied STAT1 −/− mice. H.W.V. was supported by National Institutes of Health (NIH) grant CA 74730. V.L.T. is a Leukemia and Lymphoma society fellow. This work was supported in part by NIH grant GM47017 to H.P.-W. H.P.-W. is a Howard Hughes Medical Institute investigator. This work was supported in part by Digestive Disease Research Core Center, NIH Grant # P30 DK52514.
PY - 2007/6/14
Y1 - 2007/6/14
N2 - DNA virus infection can elicit the DNA damage response in host cells, including ATM kinase activation and H2AX phosphorylation. This is considered to be the host cell response to replicating viral DNA. In contrast, we show that during infection of macrophages murine γ-herpesvirus 68 (γHV68) actively induces H2AX phosphorylation by expressing a viral kinase (orf36). γHV68-encoded orf36 kinase and its EBV homolog, BGLF4, induce H2AX phosphorylation independently of other viral genes. The process requires the kinase domain of Orf36 and is enhanced by ATM. Orf36 is important for γHV68 replication in infected animals, and orf36, H2AX, and ATM are all critical for efficient γHV68 replication in primary macrophages. Thus, activation of proximal components of the DNA damage signaling response is an active viral kinase-driven strategy required for efficient γ-herpesvirus replication.
AB - DNA virus infection can elicit the DNA damage response in host cells, including ATM kinase activation and H2AX phosphorylation. This is considered to be the host cell response to replicating viral DNA. In contrast, we show that during infection of macrophages murine γ-herpesvirus 68 (γHV68) actively induces H2AX phosphorylation by expressing a viral kinase (orf36). γHV68-encoded orf36 kinase and its EBV homolog, BGLF4, induce H2AX phosphorylation independently of other viral genes. The process requires the kinase domain of Orf36 and is enhanced by ATM. Orf36 is important for γHV68 replication in infected animals, and orf36, H2AX, and ATM are all critical for efficient γHV68 replication in primary macrophages. Thus, activation of proximal components of the DNA damage signaling response is an active viral kinase-driven strategy required for efficient γ-herpesvirus replication.
KW - DNA
KW - MICROBIO
UR - http://www.scopus.com/inward/record.url?scp=34249910944&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2007.05.008
DO - 10.1016/j.chom.2007.05.008
M3 - Article
C2 - 18005708
AN - SCOPUS:34249910944
VL - 1
SP - 275
EP - 286
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 4
ER -