期刊
VIRUSES-BASEL
卷 15, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/v15061243
关键词
parvoviruses; DNA damage response; Minute Virus of Mice
类别
Minute Virus of Mice (MVM) is an autonomous parvovirus that replicates in mouse and human cells. It localizes to cellular sites of DNA damage through the help of its non-structural phosphoprotein NS1. The localization is dependent on ATR signaling but independent of ATM or DNA-PK signaling.
Minute Virus of Mice (MVM) is an autonomous parvovirus of the Parvoviridae family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral replication centers. MVM replication induces a cellular DNA damage response that is mediated by signaling through the ATM kinase pathway, while inhibiting induction of the ATR kinase signaling pathway. However, the cellular signals regulating virus localization to cellular DNA damage response sites has remained unknown. Using chemical inhibitors to DNA damage response proteins, we have discovered that NS1 localization to cellular DDR sites is independent of ATM or DNA-PK signaling but is dependent on ATR signaling. Pulsing cells with an ATR inhibitor after S-phase entry leads to attenuated MVM replication. These observations suggest that the initial localization of MVM to cellular DDR sites depends on ATR signaling before it is inactivated by vigorous virus replication.
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