Conserved Herpesvirus Protein Kinases Target SAMHD1 to Facilitate Virus Replication

Kun Zhang, Dong Wen Lv, Renfeng Li

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

To ensure a successful infection, herpesviruses have developed elegant strategies to counterbalance the host anti-viral responses. Sterile alpha motif and HD domain 1 (SAMHD1) was recently identified as an intrinsic restriction factor for a variety of viruses. Aside from HIV-2 and the related simian immunodeficiency virus (SIV) Vpx proteins, the direct viral countermeasures against SAMHD1 restriction remain unknown. Using Epstein-Barr virus (EBV) as a primary model, we discover that SAMHD1-mediated anti-viral restriction is antagonized by EBV BGLF4, a member of the conserved viral protein kinases encoded by all herpesviruses. Mechanistically, we find that BGLF4 phosphorylates SAMHD1 and thereby inhibits its deoxynucleotide triphosphate triphosphohydrolase (dNTPase) activity. We further demonstrate that the targeting of SAMHD1 for phosphorylation is a common feature shared by beta- and gamma-herpesviruses. Together, our findings uncover an immune evasion mechanism whereby herpesviruses exploit the phosphorylation of SAMHD1 to thwart host defenses. Herpesviruses have evolved elegant strategies to dampen the host anti-viral responses. Zhang et al. discover a mechanism by which herpesviruses evade SAMHD1-mediated host defenses through phosphorylation, expanding the functional repertoire of viral protein kinases in herpesvirus biology.

Original languageEnglish (US)
Pages (from-to)449-459.e5
JournalCell Reports
Volume28
Issue number2
DOIs
StatePublished - Jul 9 2019
Externally publishedYes

Keywords

  • conserved herpesvirus protein kinases
  • cytomegalovirus
  • dNTPase
  • Epstein-Barr virus
  • infection
  • lytic replication
  • phosphorylation
  • reactivation
  • restriction factor
  • SAMHD1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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