Evidence for IFNalpha-induced, SAMHD1-independent inhibitors of early HIV-1 infection

Caroline Goujon, Torsten Schaller, Rui Pedro Galao Ribeiro Galao, Sarah M. Amie, Baek Kim, Kevin Olivieri, Stuart J. D. Neil, Michael H. Malim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)


Background: Type I interferon (IFN) treatment of some cells, including dendritic cells, macrophages and monocytic THP-1 cells, restricts HIV-1 infection and prevents viral cDNA accumulation. Sterile alpha motif and HD domain protein 1 (SAMHD1), a dGTP-regulated deoxynucleotide triphosphohydrolase, reduces HIV-1 infectivity in myeloid cells, likely by limiting dNTPs available for reverse transcription, and has been described as IFN alpha-inducible. Myeloid cell infection by HIV-1 is enhanced by HIV-2/SIVSM Vpx, which promotes SAMHD1 degradation, or by exogenous deoxyribonucleoside (dN) addition.

Findings: SAMHD1 expression was not substantially influenced by IFN alpha treatment of monocyte-derived macrophages or THP-1 cells. The contributions of SAMHD1 to the inhibition of HIV-1 infectivity by IFN alpha were assessed through the provision of Vpx, exogenous dN addition, or via RNAi-mediated SAMHD1 knock-down. Both Vpx and dN efficiently restored infection in IFN alpha-treated macrophages, albeit not to the levels seen with these treatments in the absence of IFN alpha. Similarly using differentiated THP-1 cells, the addition of Vpx or dNs, or SAMHD1 knock-down, also stimulated infection, but failing to match the levels observed without IFN alpha. Neither Vpx addition nor SAMHD1 knock-down reversed the IFN alpha-induced blocks to HIV-1 infection seen in dividing U87-MG or THP-1 cells. Therefore, altered SAMHD1 expression or function cannot account for the IFN alpha induced restriction to HIV-1 infection seen in many cells and cell lines.

Conclusion: IFN alpha establishes an anti-HIV-1 phenotype in many cell types, and appears to accomplish this without potentiating SAMHD1 function. We conclude that additional IFN alpha-induced suppressors of the early stages of HIV-1 infection await identification.

Original languageEnglish
Article number23
Pages (from-to)N/A
Number of pages6
Issue numberN/A
Publication statusPublished - 25 Feb 2013


  • HIV-1
  • Interferon
  • Restriction
  • Macrophages
  • SAMHD1
  • Vpx
  • Deoxyribonucleosides
  • CD4(+) T-CELLS
  • VPX


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