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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
- Source :
- Retrovirology, Vol 9, Iss 1, p 105 (2012), Retrovirology
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
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.
- Subjects :
- CD4-Positive T-Lymphocytes
lcsh:Immunologic diseases. Allergy
Endogeny
Biology
Virus Replication
Dendritic cells
Intracellular dNTPs
SAM Domain and HD Domain-Containing Protein 1
Downregulation and upregulation
Interferon
Virology
medicine
Humans
Viral Regulatory and Accessory Proteins
RNA, Messenger
Monomeric GTP-Binding Proteins
Regulation of gene expression
HIV-1 restriction
Research
HEK 293 cells
Reverse Transcription
Molecular biology
SAMHD1
HEK293 Cells
Infectious Diseases
Gene Expression Regulation
Cell culture
Proteolysis
HIV-1
Interferons
lcsh:RC581-607
Intracellular
HeLa Cells
medicine.drug
Subjects
Details
- ISSN :
- 17424690
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Retrovirology
- Accession number :
- edsair.doi.dedup.....2836ca259535cb310147c319462a0841