title: SAMHD1 restricts HIV-1 infection in dendritic cells (DCs) by dNTP depletion, but its expression in DCs and primary CD4+ T-lymphocytes cannot be upregulated by interferons.
abstract: BACKGROUND
  SAMHD1 is an HIV-1 restriction factor in non-dividing monocytes, dendritic cells (DCs), macrophages, and resting CD4+ T-cells. Acting as a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, SAMHD1 hydrolyzes dNTPs and restricts HIV-1 infection in macrophages and resting CD4+ T-cells by decreasing the intracellular dNTP pool. However, the intracellular dNTP pool in DCs and its regulation by SAMHD1 remain unclear. SAMHD1 has been reported as a type I interferon (IFN)-inducible protein, but whether type I IFNs upregulate SAMHD1 expression in primary DCs and CD4+ T-lymphocytes is unknown.
  
  
  RESULTS
  Here, we report that SAMHD1 significantly blocked single-cycle and replication-competent HIV-1 infection of DCs by decreasing the intracellular dNTP pool and thereby limiting the accumulation of HIV-1 late reverse transcription products. Type I IFN treatment did not upregulate endogenous SAMHD1 expression in primary DCs or CD4+ T-lymphocytes, but did in HEK 293T and HeLa cell lines. When SAMHD1 was over-expressed in these two cell lines to achieve higher levels than that in DCs, no HIV-1 restriction was observed despite partially reducing the intracellular dNTP pool.
  
  
  CONCLUSIONS
  Our results suggest that SAMHD1-mediated reduction of the intracellular dNTP pool in DCs is a common mechanism of HIV-1 restriction in myeloid cells. Endogenous expression of SAMHD1 in primary DCs or CD4+ T-lymphocytes is not upregulated by type I IFNs.
authors.affiliation: Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, Ohio 43210, USA.
authors.forename: Corine
authors.initials: C
authors.lastname: St Gelais
authors.forename: Suresh
authors.initials: S
authors.lastname: de Silva
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Amie
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Coleman
authors.forename: Heather
authors.initials: H
authors.lastname: Hoy
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hollenbaugh
authors.forename: Baek
authors.initials: B
authors.lastname: Kim
authors.forename: Li
authors.initials: L
authors.lastname: Wu
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D048348:Reverse Transcription; D000076106:SAM Domain and HD Domain-Containing Protein 1; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D012333:RNA, Messenger; C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins; D007372:Interferons; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins