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PLoS Pathog ; 17(8): e1009824, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34398933

RESUMO

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.


Assuntos
Herpes Simples/metabolismo , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Virais/metabolismo , Montagem de Vírus , Replicação Viral , Animais , Chlorocebus aethiops , Células HEK293 , Herpesvirus Humano 1/enzimologia , Humanos , Monoéster Fosfórico Hidrolases/genética , Células Vero , Proteínas Virais/genética , Liberação de Vírus
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