Journal
RETROVIROLOGY
Volume 9, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1742-4690-9-105
Keywords
HIV-1 restriction; SAMHD1; Dendritic cells; Interferon; Intracellular dNTPs
Categories
Funding
- National Institutes of Health (NIH) [AI098524, AI102822, GM104198, AI049781]
- Public Health Preparedness for Infectious Diseases Program of The Ohio State University
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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.
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