Background:
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 ex vivo, after their activation and in vitro HIV-1 infection. We performed phenotype analyzes and functional studies using CD4+ T cells from peripheral blood and lymph nodes from cohorts of HIV-1 infected subjects under anti-retroviral 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 SAMHD1low cells are highly differentiated, exhibit a large proportion of Ki67+ cycling cells and are enriched in Th17 cells. Importantly, memory SAMHD1low cells were depleted from peripheral blood of HIV-infected individuals. We also found that lymph node follicular helper T (Tfh) cells lacked the expression of SAMHD1, which was accompanied by a higher susceptibility to HIV-1 infection in vitro.
Conclusions:
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, e.g. Th17 and Tfh 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.