Increased expression of SAMHD1 in a subset of HIV-1 elite controllers

J Antimicrob Chemother. 2014 Nov;69(11):3057-60. doi: 10.1093/jac/dku276. Epub 2014 Jul 25.

Abstract

Objectives: SAMHD1 and the CDKN1A (p21) cyclin-dependent kinase inhibitor have been postulated to mediate HIV-1 restriction in CD4+ cells. We have shown that p21 affects HIV replication through its effect on SAMHD1. Thus, we aimed at evaluating the expression of SAMHD1 and p21 in different HIV+ phenotypic groups.

Patients and methods: We evaluated SAMHD1 and CDKN1A mRNA expression in CD4+ T cells from HIV+ individuals including elite controllers (n = 12), individuals who control HIV without the need for antiretroviral treatment, viraemic progressors (n = 10) and HIV-1 seronegative healthy donors (n = 14). Immunological variables were measured by flow cytometry.

Results: We show that a subset of HIV+ elite controllers with lower T cell proliferation levels (Ki67+ cells) expressed higher SAMHD1 compared with healthy donors or viraemic progressors. Conversely, there was no difference in p21 expression before or after T cell activation with a bispecific CD3/CD8 antibody.

Conclusions: Our results suggest that SAMHD1 may play a role in controlling virus replication in HIV+ individuals and slow the rate of disease progression.

Keywords: p21; restriction factors; viral control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Enzymologic*
  • HIV-1 / enzymology*
  • Humans
  • Ki-67 Antigen / biosynthesis
  • Monomeric GTP-Binding Proteins / biosynthesis*
  • Phenotype*
  • SAM Domain and HD Domain-Containing Protein 1
  • Virus Replication / physiology*

Substances

  • Ki-67 Antigen
  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human
  • Monomeric GTP-Binding Proteins