Immunological effector mechanisms in HIV-1 elite controllers

HIV-1 elite controllers encompass small populations of people infected with HIV-1 who can spontaneously control plasma viral loads below the limit of detection, in the absence of antiretroviral treatment. Antiviral immune responses are likely to contribute to such an impressive HIV-1 disease outcome. In this review, we discuss recent novel findings regarding antiviral innate and adaptive immune responses in elite controllers.

Elite controllers maintain a pool of infected cells in which intact HIV-1 proviruses are more frequently integrated into noncoding regions of the host genome, likely conferring a state of deep latency. This atypical viral reservoir configuration is best explained by potent antiviral immune responses that can successfully eliminate virally infected cells in which proviruses are integrated into permissive chromatin. However, identifying the specific type and nature of this immune selection pressure represents a formidable challenge. Recent studies continue to support the role of HIV-1-specific CD8+ T cells as the main driver of elite immune control of HIV-1, however, increasing evidence suggests that their role is complemented by a fine-tuned interplay with innate immune cell subsets. Therefore, the combination of different immune effector mechanisms may shape antiviral immunity in elite controllers.

Understanding the complex immune mechanisms responsible for natural, drug-free HIV-1 control represents a premier avenue to find and develop interventions for a cure of HIV-1 infection. Future single-cell assays designed to uncover the full genetic, epigenetic, transcriptional and functional complexity of antiviral immune responses in elite controllers may allow us to define correlates of antiviral immune protection in greater detail.