The sooner the better: innate immunity as a path toward the HIV cure

•Virus dissemination occurs rapidly after mucosal SIV infection.•Early innate host immune response after HIV/SIV infection dictates viral load at acute phase.•Specific Interferon signatures are associated to viral dissemination.•Inflammasome activation at early time-points inhibits intrinsic innate anti-viral responses and leads to virus dissemination and seeding.

To combat the diverse pathogens that infect humans, the immune system has evolved complex and diverse transcriptional signatures, which drive differential cellular and humoral responses. These signatures are induced by immune receptor sensing of pathogens and by cytokines produced at the earliest onset of infection. The specific nature of immune activation is as critical to pathogen clearance as the induction of an adaptive immune response. This is particularly true for HIV, which has developed numerous immune evasion mechanisms. In this review, we will highlight recent findings that show the differential role for early innate immune responses in promoting infection versus clearance and demonstrate the need for continued research on these pathways for development of effective HIV treatments.