dNTP depletion and beyond: the multifaceted nature of SAMHD1-mediated viral restriction

J Virol. 2025 May 20;99(5):e0030225. doi: 10.1128/jvi.00302-25. Epub 2025 Apr 25.

Abstract

SAMHD1 is a dNTPase of mammalian cells. In 2011, SAMHD1 was found to be a host restriction factor against retroviruses through dNTP reduction. Recent research provides evidence that the antiviral mechanisms of SAMHD1 cannot be explained solely by its dNTPase activity. Instead, the versatility of SAMHD1-mediated restriction of various viruses suggests that its antiviral mechanisms extend beyond dNTP depletion. This explains the multifaceted and broad restriction functions of SAMHD1 that play a significant role in innate antiviral immunity.

Keywords: DNA viruses; RNA viruses; SAMHD1; dNTP depletion; dNTPase; innate immunity; restriction factor; retroviruses.

Publication types

  • Review

MeSH terms

  • Animals
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate
  • Nucleotides* / metabolism
  • SAM Domain and HD Domain-Containing Protein 1* / metabolism
  • Virus Replication

Substances

  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human
  • Nucleotides