Comprehensive phosphoproteomics analysis of herpesvirus pathogenicity

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790434
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: The University of Tokyo
• Principal Investigator: KATO Akihisa 東京大学, 医科学研究所, 助教 (40581187)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 単純ヘルペスウイルス / リン酸化プロテオーム解析 / vdUTPase / Us3 / 神経病原性

Outline of Final Research Achievements

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.

Free Research Field

ウイルス学