Journal article
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
Retrovirology, Vol.9(1), pp.105-105
2012
DOI: 10.1186/1742-4690-9-105
PMCID: PMC3527137
PMID: 23231760
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.
Details
- Title: Subtitle
- 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
- Creators
- Corine St Gelais - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, 43210, USASuresh de Silva - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, 43210, USASarah M Amie - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, 43210, USAChristopher M Coleman - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, 43210, USAHeather Hoy - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, 43210, USAJoseph A Hollenbaugh - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, 43210, USABaek Kim - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, 43210, USALi Wu - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, 43210, USA
- Resource Type
- Journal article
- Publication Details
- Retrovirology, Vol.9(1), pp.105-105
- Publisher
- BioMed Central
- DOI
- 10.1186/1742-4690-9-105
- PMID
- 23231760
- PMCID
- PMC3527137
- ISSN
- 1742-4690
- eISSN
- 1742-4690
- Language
- English
- Date published
- 2012
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984002377302771
Metrics
27 Record Views