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Identification of a herpes simplex virus 1 gene encoding neurovirulence factor by chemical proteomics.

Abstract：

:Identification of the complete set of translated genes of viruses is important to understand viral replication and pathogenesis as well as for therapeutic approaches to control viral infection. Here, we use chemical proteomics, integrating bio-orthogonal non-canonical amino acid tagging and high-resolution mass spectrometry, to characterize the newly synthesized herpes simplex virus 1 (HSV-1) proteome in infected cells. In these infected cells, host cellular protein synthesis is shut-off, increasing the chance to preferentially detect viral proteomes. We identify nine previously cryptic orphan protein coding sequences whose translated products are expressed in HSV-1-infected cells. Functional characterization of one identified protein, designated piUL49, shows that it is critical for HSV-1 neurovirulence in vivo by regulating the activity of virally encoded dUTPase, a key enzyme that maintains accurate DNA replication. Our results demonstrate that cryptic orphan protein coding genes of HSV-1, and probably other large DNA viruses, remain to be identified.

journal_name

Nat Commun

journal_title

Nature communications

authors

Kato A,Adachi S,Kawano S,Takeshima K,Watanabe M,Kitazume S,Sato R,Kusano H,Koyanagi N,Maruzuru Y,Arii J,Hatta T,Natsume T,Kawaguchi Y

doi

10.1038/s41467-020-18718-9

subject

Has Abstract

pub_date

2020-09-29 00:00:00

pages

4894

issue

1

issn

2041-1723

pii

10.1038/s41467-020-18718-9

journal_volume

11

pub_type

杂志文章

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