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

N Ruffin, V Brezar, D Ayinde, C Lefebvre… - Aids, 2015 - journals.lww.com
N Ruffin, V Brezar, D Ayinde, C Lefebvre, JS Zur Wiesch, J van Lunzen, M Bockhorn…
Aids, 2015journals.lww.com
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 …
Abstract
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 low cells are highly differentiated, exhibit a large proportion of Ki67+ cycling cells and are enriched in T-helper 17 cells. Importantly, memory SAMHD1 low 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.
Lippincott Williams & Wilkins