Natural killer cells during acute HIV-1 infection: clues for HIV-1 prevention and therapy

Despite progress in preexposure prophylaxis, the number of newly diagnosed cases with HIV-1 remains high, highlighting the urgent need for preventive and therapeutic strategies to reduce HIV-1 acquisition and limit disease progression. Early immunological events, occurring during acute infection, are key determinants of the outcome and course of disease. Understanding early immune responses occurring before viral set-point is established, is critical to identify potential targets for prophylactic and therapeutic approaches. Natural killer (NK) cells represent a key cellular component of innate immunity and contribute to the early host defence against HIV-1 infection, modulating the pathogenesis of acute HIV-1 infection (AHI). Emerging studies have identified tools for harnessing NK cell responses and expanding specialized NK subpopulations with adaptive/memory features, paving the way for development of novel HIV-1 therapeutics. This review highlights the knowns and unknowns regarding the role of NK cell subsets in the containment of acute HIV-1 infection, and summarizes recent advances in selectively augmenting NK cell functions through prophylactic and therapeutic interventions.