Type I interferon and HIV: Subtle balance between antiviral activity, immunopathogenesis and the microbiome

Graphical abstract
Highlights • Induction and action of IFN during acute and chronic HIV-1 infection. • Host and viral factors influencing IFN response in HIV-1 infected patients. • Type I IFN and IFNα subtypes signatures and their antiviral activity during HIV-1 infection. • The microbiome and intestinal IFN responses relationship in HIV-1 infection and disease.
Type I interferon (IFN) response initially limits HIV-1 spread and may delay disease progression by stimulating several immune system components. Nonetheless, persistent exposure to type I IFN in the chronic phase of HIV-1 infection is associated with desensitization and/or detrimental immune activation, thereby hindering immune recovery and fostering viral persistence. This review provides a basis for understanding the complexity and function of IFN pleiotropic activity in HIV-1 infection. In particular, the dichotomous role of the IFN response in HIV-1 immunopathogenesis will be discussed, highlighting recent advances in the dynamic modulation of IFN production in acute versus chronic infection, expression signatures of IFN subtypes, and viral and host factors affecting the magnitude of IFN response during HIV-1 infection. Lastly, the review gives a forward-looking perspective on the interplay between microbiome compositions and IFN response.