Eva Riveira-Muñoz1, Alba Ruiz1, Eduardo Pauls1, Marc Permanyer1, Roger Badia1, Beatriz Mothe1, Manel Crespo2, Bonaventura Clotet1, Christian Brander3, Ester Ballana1, José A Esté4. 1. AIDS Research Institute-IrsiCaixa and AIDS Unit, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. 2. Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain. 3. AIDS Research Institute-IrsiCaixa and AIDS Unit, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 4. AIDS Research Institute-IrsiCaixa and AIDS Unit, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain jaeste@irsicaixa.es.
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.
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.
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