T cells with low CD2 levels express reduced restriction factors and are preferentially infected in therapy naïve chronic HIV-1 patients

J Int AIDS Soc. 2017 Sep 19;20(1):21865. doi: 10.7448/IAS.20.1.21865.

Abstract

Introduction: Restriction factors (RFs) suppress HIV-1 in cell lines and primary cell models. Hence, RFs might be attractive targets for novel antiviral strategies, but their importance for virus control in vivo is controversial.

Methods: We profiled the expression of RFs in primary blood-derived mononuclear cells (PBMC) from therapy-naïve HIV-1 patients and quantified infection.

Results: Overall, there was no correlation between individual RF expression and HIV-1 status in total PBMC. However, we identified a T cell population with low levels of intracellular CD2 and reduced expression of SAMHD1, p21 and SerinC5. CD2low T cells with reduced RF expression were markedly positive for HIV-1 p24. In contrast, CD2+ T cells were less infected and expressed higher levels of RFs. CD2low T cell infection correlated with viral loads and was associated with HIV-1 disease progression.

Conclusions: In untreated therapy naïve chronic HIV-1 patients, RF expression in T cells is associated with CD2 expression and seems to influence viral loads. Our study suggests that RFs help to control HIV-1 infection in certain T cells in vivo and supports the potential for RFs as promising targets for therapeutic intervention.

Keywords: HIV-1; RISP; SAMHD1; SerinC5; Tetherin; in vivo relevance; p21; restriction factors.

MeSH terms

  • Adult
  • Aged
  • Female
  • HIV Infections / genetics*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • SAM Domain and HD Domain-Containing Protein 1 / genetics
  • SAM Domain and HD Domain-Containing Protein 1 / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Viral Load

Substances

  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human