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

TY - JOUR

T1 - Low SAMHD1 expression following T-cell activation and proliferation renders CD4+ T cells susceptible to HIV-1

AU - Ruffin, Nicolas

AU - Brezar, Vedran

AU - Ayinde, Diana

AU - Lefebvre, Cécile

AU - Schulze Zur Wiesch, Julian

AU - Lunzen, Jan

AU - Bockhorn, Maximilian

AU - Schwartz, Olivier

AU - Hocini, Hakim

AU - Lelievre, Jean-Daniel

AU - Banchereau, Jacques

AU - Levy, Yves

AU - Seddiki, Nabila

PY - 2015/3/13

Y1 - 2015/3/13

N2 - OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.

AB - OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.

U2 - 10.1097/QAD.0000000000000594

DO - 10.1097/QAD.0000000000000594

M3 - SCORING: Journal article

C2 - 25715102

VL - 29

SP - 519

EP - 530

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 5

ER -