期刊论文详细信息
PLoS Pathogens
Parvovirus Minute Virus of Mice Induces a DNA Damage Response That Facilitates Viral Replication
Sebastien Landry1  Matthew D. Weitzman1  Meredith E. Davis2  David J. Pintel2  Richard O. Adeyemi2 
[1] Salk Institute, La Jolla, California, United States of America;University of Missouri-Columbia, School of Medicine, Columbia, Missouri, United States of America
关键词: Viral replication;    DNA replication;    DNA damage;    Phosphorylation;    Cell cycle;    cell division;    Signal inhibition;    Antibodies;    Cell cycle inhibitors;   
DOI  :  10.1371/journal.ppat.1001141
学科分类:生物科学(综合)
来源: Public Library of Science
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【 摘 要 】

Infection by DNA viruses can elicit DNA damage responses (DDRs) in host cells. In some cases the DDR presents a block to viral replication that must be overcome, and in other cases the infecting agent exploits the DDR to facilitate replication. We find that low multiplicity infection with the autonomous parvovirus minute virus of mice (MVM) results in the activation of a DDR, characterized by the phosphorylation of H2AX, Nbs1, RPA32, Chk2 and p53. These proteins are recruited to MVM replication centers, where they co-localize with the main viral replication protein, NS1. The response is seen in both human and murine cell lines following infection with either the MVMp or MVMi strains. Replication of the virus is required for DNA damage signaling. Damage response proteins, including the ATM kinase, accumulate in viral-induced replication centers. Using mutant cell lines and specific kinase inhibitors, we show that ATM is the main transducer of the signaling events in the normal murine host. ATM inhibitors restrict MVM replication and ameliorate virus-induced cell cycle arrest, suggesting that DNA damage signaling facilitates virus replication, perhaps in part by promoting cell cycle arrest. Thus it appears that MVM exploits the cellular DNA damage response machinery early in infection to enhance its replication in host cells.

【 授权许可】

CC BY   

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