Research Project
Grant-in-Aid for Young Scientists (B)
Herpes simplex virus 1 (HSV-1) encodes Us3 protein kinase and a dUTPase (vdUTPase), which are both critical for neurovirulence in the central nerve system (CNS) of mice. We showed that Us3 phosphorylated vdUTPase to up-regulate its enzymatic activity. This phosphorylation was specifically required for neurovirulence in the CNS of mice, but not for pathogenic effects in mouse eyes and vaginas. Low endogenous cellular dUTPase activity in cell cultures and in vivo was linked to lower replication and virulence of a recombinant virus carrying a mutation that precluded phosphorylation of vdUTPase, and overexpression of cellular dUTPase restored HSV-1 neurovirulence in the CNS by the recombinant virus. Our results supported the hypothesis that CNS-specific neurovirulence of HSV-1 involved strict regulation of vdUTPase activity by Us3 phosphorylation, to compensate for the low cellular dUTPase activity in the CNS, to produce efficient viral replication.
All 2015 2014 2013 2012 Other
All Journal Article (16 results) (of which Peer Reviewed: 16 results, Open Access: 12 results, Acknowledgement Compliant: 8 results) Presentation (43 results) Book (1 results) Remarks (1 results)
Journal of Virology
Volume: 印刷中
Microbiology and Immunology
Volume: 印刷中 Issue: 6 Pages: 331-7
10.1111/1348-0421.12255
40020510068
Volume: 89 Issue: 3 Pages: 1879-88
10.1128/jvi.03079-14
Volume: 89 Issue: 1 Pages: 241-8
10.1128/jvi.02497-14
Volume: 88 Issue: 18 Pages: 10624-34
10.1128/jvi.01634-14
Volume: 88 Issue: 14 Pages: 7776-85
10.1128/jvi.00603-14
Volume: 88 Issue: 13 Pages: 7445-54
10.1128/jvi.01057-14
Jounarl of Virology
Volume: 88 Issue: 9 Pages: 4657-67
10.1128/jvi.00137-14
Volume: 88 Issue: 5 Pages: 2775-85
10.1128/jvi.03300-13
Volume: VOL. 88 Issue: 4 Pages: 2359-2364
10.1128/jvi.03621-13
Volume: 58 Issue: 1 Pages: 31-37
10.1111/1348-0421.12108
Molecular cell
Volume: 53 Issue: 3 Pages: 393-406
10.1016/j.molcel.2014.01.009
J Virol
Volume: 88 Issue: 1 Pages: 655-666
10.1128/jvi.02710-13
Volume: 87 Issue: 16 Pages: 9323-9332
10.1128/jvi.01581-13
PLos One
Volume: 8 Issue: 8 Pages: e72050-e72050
10.1371/journal.pone.0072050
neurovirulence
Volume: 86(9) Issue: 9 Pages: 5264-77
10.1128/jvi.06913-11
http://www.ims.u-tokyo.ac.jp/kawaguchi-lab/kawaguchilabtop.html