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

Akihisa Kato, Shungo Adachi, Shuichi Kawano, Kousuke Takeshima, Mizuki Watanabe, Shinobu Kitazume, Ryota Sato, Hideo Kusano, Naoto Koyanagi, Yuhei Maruzuru, Jun Arii, Tomohisa Hatta, Tohru Natsume () and Yasushi Kawaguchi ()
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Akihisa Kato: The University of Tokyo
Shungo Adachi: Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST)
Shuichi Kawano: The University of Electro-Communications
Kousuke Takeshima: The University of Tokyo
Mizuki Watanabe: The University of Tokyo
Shinobu Kitazume: Fukushima Medical University, Fukushima City
Ryota Sato: The University of Tokyo
Hideo Kusano: Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST)
Naoto Koyanagi: The University of Tokyo
Yuhei Maruzuru: The University of Tokyo
Jun Arii: The University of Tokyo
Tomohisa Hatta: Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST)
Tohru Natsume: Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST)
Yasushi Kawaguchi: The University of Tokyo

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18718-9

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