Immune Control of HIV

The uman mmunodeficiency irus (HIV) infection of the immune cells expressing the luster of ifferentiation cell surface glycoprotein (CD4 cells) causes progressive decline of the immune system and leads to the cquired mmunoeficiency yndrome (AIDS). The ongoing global HIV/AIDS pandemic has already claimed over 35 million lives. Even after 37 years into the epidemic, neither a cure is available for the 37 million eople iving with (PLHIV) nor is a vaccine discovered to avert the millions of new HIV infections that continue to occur each year. If left untreated, HIV infection typically progresses to AIDS and, ultimately, causes death in a majority of PLHIV. The recommended ombination ntietroviral herapy (cART) suppresses virus replication and viremia, prevents or delays progression to AIDS, reduces transmission rates, and lowers HIV-associated mortality and morbidity. However, because cART does not eliminate HIV, and an enduring pool of infected resting memory CD4 T cells (latent HIV reservoir) is established early on, any interruption to cART leads to a relapse of viremia and disease progression. Hence, strict adherence to a life-long cART regimen is mandatory for managing HIV infection in PLHIV. The HIV-1-specific ytooxic cells expressing the CD8 glycoprotein (CD8 CTL) limit the virus replication by recognizing the viral antigens presented by uman eukocyte ntigen (HLA) class I molecules on the infected cell surface and killing those cells. Nevertheless, CTLs fail to durably control HIV-1 replication and disease progression in the absence of cART. Intriguingly, <1% of cART-naive HIV-infected individuals called elite controllers/IV ontrollers (HCs) exhibit the core features that define a HIV-1 "functional cure" outcome in the absence of cART: durable viral suppression to below the limit of detection, long-term non-progression to AIDS, and absence of viral transmission. Robust HIV-1-specific CTL responses and prevalence of protective HLA alleles associated with enduring HIV-1 control have been linked to the HC phenotype. An understanding of the molecular mechanisms underlying the CTL-mediated suppression of HIV-1 replication and disease progression in HCs carrying specific protective HLA alleles may yield promising insights towards advancing the research on HIV cure and prophylactic HIV vaccine.