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

Li Wu³  Baek Kim²  Joseph A Hollenbaugh²  Heather Hoy¹  Christopher M Coleman¹  Sarah M Amie²  Suresh de Silva¹  Corine St Gelais¹ 

[1] Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, Ohio, 43210, USA;Department of Microbiology & Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 672, Rochester, New York, 14642, USA;Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, 43210, USA

关键词: Intracellular dNTPs;    Interferon;    Dendritic cells;    SAMHD1;    HIV-1 restriction;   

Others  :  1209219
DOI  :  10.1186/1742-4690-9-105

 received in 2012-10-14, accepted in 2012-11-29,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 St Gelais et al.; licensee BioMed Central Ltd.

【 图 表 】

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