The persistence of the HIV reservoir is a major obstacle to potential cures. In Nature, Benkirane and colleagues show that upregulation of CD32a, the low-affinity IgG receptor, is specific for HIV-1-infected quiescent CD4+ T cells. The authors create an experimental model of infection of resting CD4+ T cells, which are usually nonpermissive to HIV-1, by transfecting peripheral blood mononuclear cells with the SIV accessory protein Vpx, which degrades the restriction factor SAMHD1. Among the 16 transmembrane-protein-encoding genes that are specifically upregulated by HIV-1 infection in resting CD4+ T cells, FCGR2A (encoding CD32a) is upregulated 50-fold compared with its expression in non-infected cells. CD32a is not induced by productive infection with HIV-1 in proliferating CD4+ T cells. In 12 HIV-1-infected individuals undergoing antiretroviral therapy, CD32ahiCD4+ T cells were found to harbor up to three copies of HIV-1 DNA per cell, make up 26–86% of the CD4+ T cell viral reservoir, and harbor replication-competent proviruses. Thus, CD32a marks CD4+ T cells in the viral reservoir.

Nature 543, 564–567 (2017)