Heightened expression of type I interferon signaling genes in CD4+ T cells from acutely HIV-1 infected women is associated with lower viral loads

In this study, we have identified a number of differentially expressed genes in naïve, central memory, and effector memory CD4 T cells of HIV-infected women compared to men, with consistent elevated expression of genes linked to type 1 interferon signaling. Moreover, after controlling for differences in VL and CD4+ T cell count genes within the type I interferon (IFN) signaling pathway were further shown to be more highly expressed in women, whereas, those genes more highly expressed in men showed no such enrichment. A subset of the genes highly expressed in women were further identified, including several involved in type I IFN signaling in response to viral infections (IRF7, DDX58, SAMHD1, OAS2, and TRIM14), that are both more highly expressed in CD4+ T cells from women and negatively correlated with VL, suggesting that they play a role in the comparative control of VL observed in women. We have performed bulk RNA-seq experiments comparing gene expression between CD4+ T cells from acutely HIV-1 infected men and women in Zambia, since we observe lower viral load (VL) despite higher CD4+ T cell activation in these women during acute/early infection. We performed analysis on both individual CD4+ T cell subsets (Naive, Central Memory and Effector Memory) as well as combined CD4 T cells) controlling for CD4 T cell counts and viral load.