Double trouble: HIV latency and CTL escape

Abstract

HIV can enter a state of latency that allows it to persist for decades in antiretroviral drug-treated patients. In a recent Nature paper, Deng et al. (2015) show that this latent reservoir also contains a large number of cytotoxic T lymphocyte escape mutants, presenting another challenge to HIV cure efforts.

Figure 1. CTL Escape Mutant Viruses in the Latent HIV Reservoir

(A) Soon after HIV transmission, latently infected CD4+ T cells contain HIV genomes encoding primarily CTL-susceptible epitopes (green cells). However, these are replaced over time with viruses encoding CTL escape mutations (red cells). Early initiation of antiretroviral therapy (ART) can prevent this accumulation of resistant viruses. (B) Upon expression of latent HIV, cells from patients that initiated ART early are susceptible to killing by CTL specific for wild-type immunodominant HIV epitopes. (C) HIV variants isolated from individuals treated later in infection (>3 months post-infection) are resistant to killing by many CTLs that target common epitopes. Yet, these cells can still be killed by appropriately stimulated CTLs specific for other non-mutated epitopes. Hence, elimination of the latent reservoir may require both activation of latent virus expression and the stimulation of a broad CTL response.