4.7 Article

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

Journal

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 69, Issue 11, Pages 3057-3060

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/jac/dku276

Keywords

restriction factors; p21; viral control

Funding

  1. Spanish MINECO [BFU2012-31569, PI13/01083]
  2. HIVACAT
  3. Bill and Melinda Gates Foundation
  4. Gala Contra la SIDA
  5. ICREA Funding Source: Custom

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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. We evaluated SAMHD1 and CDKN1A mRNA expression in CD4+ T cells from HIV+ individuals including elite controllers (naEuroS=aEuroS12), individuals who control HIV without the need for antiretroviral treatment, viraemic progressors (naEuroS=aEuroS10) and HIV-1 seronegative healthy donors (naEuroS=aEuroS14). Immunological variables were measured by flow cytometry. 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. Our results suggest that SAMHD1 may play a role in controlling virus replication in HIV+ individuals and slow the rate of disease progression.

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