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: Corine St Gelais, Suresh de Silva, Sarah M Amie, Christopher M Coleman, Heather Hoy, Joseph A Hollenbaugh, Baek Kim, Li Wu
• Journal: Retrovirology (Retrovirology) Vol. 9 Pg. 105 (Dec 11 2012) ISSN: 1742-4690 [Electronic] England
• PMID: 23231760 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• VPX protein, Simian immunodeficiency virus
• Viral Regulatory and Accessory Proteins
• Interferons
• SAM Domain and HD Domain-Containing Protein 1
• SAMHD1 protein, human
• Monomeric GTP-Binding Proteins

Topics

• CD4-Positive T-Lymphocytes (drug effects, metabolism, virology)
• Dendritic Cells (drug effects, metabolism, virology)
• Gene Expression Regulation (drug effects)
• HEK293 Cells
• HIV-1 (physiology)
• HeLa Cells
• Humans
• Interferons (pharmacology)
• Monomeric GTP-Binding Proteins (genetics, metabolism)
• Proteolysis
• RNA, Messenger (genetics, metabolism)
• Reverse Transcription
• SAM Domain and HD Domain-Containing Protein 1
• Viral Regulatory and Accessory Proteins (metabolism)
• Virus Replication