MAVSGenetic Variation Is Associated with Decreased HIV-1 Replication In Vitro and Reduced CD4+T Cell Infection in HIV-1-Infected Individuals

The mitochondrial antiviral protein MAVS is a key player in the induction of antiviral responses; however, human immunodeficiency virus 1 (HIV-1) is able to suppress these responses. Two linked single nucleotide polymorphisms (SNPs) in theMAVSgene render MAVS insensitive to HIV-1-dependent suppression, and have been shown to be associated with a lower viral load at set point and delayed increase of viral load during disease progression. Here, we studied the underlying mechanisms involved in the control of viral replication in individuals homozygous for thisMAVSgenotype. We observed that individuals with theMAVSminor genotype had more stable total CD4(+)T cell counts during a 7-year follow up and had lower cell-associated proviral DNA loads. Genetic variation inMAVSdid not affect immune activation levels; however, a significantly lower percentage of naive CD4(+)but not CD8(+)T cells was observed in theMAVSminor genotype. In vitro HIV-1 infection of peripheral blood mononuclear cells (PBMCs) from healthy donors with theMAVSminor genotype resulted in decreased viral replication. Although the precise underlying mechanism remains unclear, our data suggest that the protective effect of theMAVSminor genotype may be exerted by the initiation of local innate responses affecting viral replication and CD4(+)T cell susceptibility.