Low SAMHD1 expression following T-cell activation and proliferation renders CD4+ T cells susceptible to HIV-1.

Nicolas Ruffin (1, 2, 3) , Vedran Brezar (1, 2, 3) , Diana Ayinde (4) , Cécile Lefebvre (1, 2, 3) , Julian Schulze Zur Wiesch (5, 6) , Jan van Lunzen (5, 6) , Maximilian Bockhorn (7) , Olivier Schwartz (4) , Hakim Hocini (1, 2, 3) , Jean-Daniel Lelievre (2, 3, 8, 9) , Jacques Banchereau (1, 2, 3, 8, 10) , Yves Levy (1, 2, 3, 9) , Nabila Seddiki (1, 2, 3)

1 Physiopathologie et immunothérapies dans l’infection VIH
2 UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12
3 VRI - Vaccine Research Institute [Créteil, France]
4 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
5 Department of Internal Medicine
6 Leibniz Institute for Experimental Virology
7 General, Visceral and Thoracic Surgery Department
8 Hôpital H. Mondor - A. Chenevier
9 AP-HP - Immunologie clinique et maladies infectieuses
10 JAX - The Jackson Laboratory [Bar Harbor]

HIV-1 replication depends on the state of cell activation and division. It is established that SAMHD1 restricts HIV-1 infection of resting CD4 T cells. The modulation of SAMHD1 expression during T-cell activation and proliferation, however, remains unclear, as well as a role for SAMHD1 during HIV-1 pathogenesis. SAMHD1 expression was assessed in CD4 T cells after their activation and in-vitro HIV-1 infection. We performed phenotype analyzes using flow cytometry on CD4 T cells from peripheral blood and lymph nodes from cohorts of HIV-1-infected individuals under antiretroviral treatment or not, and controls. We show that SAMHD1 expression decreased during CD4 T-cell proliferation in association with an increased susceptibility to in-vitro HIV-1 infection. Additionally, circulating memory CD4 T cells are enriched in cells with low levels of SAMHD1. These SAMHD1 cells are highly differentiated, exhibit a large proportion of Ki67 cycling cells and are enriched in T-helper 17 cells. Importantly, memory SAMHD1 cells were depleted from peripheral blood of HIV-infected individuals. We also found that follicular helper T cells present in secondary lymphoid organs lacked the expression of SAMHD1, which was accompanied by a higher susceptibility to HIV-1 infection in vitro. We demonstrate that SAMHD1 expression is decreased during CD4 T-cell activation and proliferation. Also, CD4 T-cell subsets known to be more susceptible to HIV-1 infection, for example, T-helper 17 and follicular helper T cells, display lower levels of SAMHD1. These results pin point a role for SAMHD1 expression in HIV-1 infection and the concomitant depletion of CD4 T cells.

Mots clés: HIV restriction; HIV-1; lymphocyte activation; SAMHD1; T-helper 17 cells

Domaines: Sciences du Vivant [q-bio]; Biologie cellulaire; Virologie

Nicolas Ruffin, Vedran Brezar, Diana Ayinde, Cécile Lefebvre, Julian Schulze Zur Wiesch, et al.. Low SAMHD1 expression following T-cell activation and proliferation renders CD4+ T cells susceptible to HIV-1.. AIDS. Official journal of the international AIDS Society, 2015, 29 (5), pp.519-30. ⟨10.1097/QAD.0000000000000594⟩. ⟨pasteur-01372413⟩