T cells with low CD2 levels express reduced restriction factors and are preferentially infected in therapy naïve chronic HIV-1 patients

Introduction: Restriction factors (RFs) suppress HIV-1 in cell lines and primary cell models. Hence, RFs might be attractive targets for novel antiviral strategies, but their importance for virus control in vivo is controversial. Methods: We profiled the expression of RFs in primary blood-derived mononuclear cells (PBMC) from therapy-naïve HIV-1 patients and quantified infection. Results: Overall, there was no correlation between individual RF expression and HIV-1 status in total PBMC. However, we identified a T cell population with low levels of intracellular CD2 and reduced expression of SAMHD1, p21 and SerinC5. CD2(low) T cells with reduced RF expression were markedly positive for HIV-1 p24. In contrast, CD2+ T cells were less infected and expressed higher levels of RFs. CD2(low) T cell infection correlated with viral loads and was associated with HIV-1 disease progression. Conclusions: In untreated therapy naïve chronic HIV-1 patients, RF expression in T cells is associated with CD2 expression and seems to influence viral loads. Our study suggests that RFs help to control HIV-1 infection in certain T cells in vivo and supports the potential for RFs as promising targets for therapeutic intervention.