Upregulation of IFN-stimulated genes persists beyond the transitory broad immunologic changes of acute HIV-1 infection

Chronic immune activation during HIV-1 infection contributes to morbidity and mortality in people living with HIV. To elucidate the underlying biological pathways, we evaluated whole blood gene expression trajectories from before, through acute, and into chronic HIV-1 infection. Interferon-stimulated genes, including MX1, IFI27 and ISG15, were upregulated during acute infection, remained elevated into chronic infection, and were strongly correlated with plasma HIV-1 RNA as well as TNF-α and CXCL10 cytokine levels. In contrast, genes involved in cellular immune responses, such as CD8A, were upregulated during acute infection before reaching a peak and returning to near pre-infection levels in chronic infection. Our results indicate that chronic immune activation during HIV-1 infection is characterized by persistent elevation of a narrow set of interferon-stimulated genes and innate cytokines. These findings raise the prospect of devising a targeted intervention to restore healthy immune homeostasis in people living with HIV-1. [Display omitted] •On HIV infection, HIV RNA and CD8+T cells increased rapidly to a peak level•Genes involved in T cell responses were only transiently upregulated•Select interferon-stimulated genes remained upregulated into chronic HIV infection•Persistently upregulated ISGs were associated with HIV RNA and CXCL10 levels Molecular physiology; Immunology; Virology