Open AccesspUL21 is a viral phosphatase adaptor that promotes herpes simplex virus replication and spread
Author(s) -
Tomasz H. Benedyk,
Julia Muenzner,
Viv Connor,
Yue Han,
Katherine A. Brown,
Kaveesha J. Wijesinghe,
Yunhui Zhuang,
Susanna Colaco,
Guido A. Stoll,
Owen S. Tutt,
Stanislava Svobodova,
Dmitri I. Svergun,
Neil Bryant,
Janet E. Deane,
Andrew E. Firth,
Cy M. Jeffries,
Colin M. Crump,
Stephen C. Graham
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009824
Subject(s) - herpes simplex virus , biology , signal transducing adaptor protein , viral replication , virus , virology , dephosphorylation , phosphatase , microbiology and biotechnology , single stranded binding protein , protein phosphatase 1 , phosphorylation , genetics , dna binding protein , gene , transcription factor
The herpes simplex virus (HSV)-1 protein pUL21 is essential for efficient virus replication and dissemination. While pUL21 has been shown to promote multiple steps of virus assembly and spread, the molecular basis of its function remained unclear. Here we identify that pUL21 is a virus-encoded adaptor of protein phosphatase 1 (PP1). pUL21 directs the dephosphorylation of cellular and virus proteins, including components of the viral nuclear egress complex, and we define a conserved non-canonical linear motif in pUL21 that is essential for PP1 recruitment. In vitro evolution experiments reveal that pUL21 antagonises the activity of the virus-encoded kinase pUS3, with growth and spread of pUL21 PP1-binding mutant viruses being restored in adapted strains where pUS3 activity is disrupted. This study shows that virus-directed phosphatase activity is essential for efficient herpesvirus assembly and spread, highlighting the fine balance between kinase and phosphatase activity required for optimal virus replication.