Journal Article

Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis

Parker, Rachel, Tang, Jianming, Scully, Eileen P., Palmer, Christine D., Kilembe, William, Price, Matt A., Macharia, Gladys N., Nganou-Makamdop, Krystelle, Michelo, Clive M., Wiener, Howard W., Kopycinski, Jakub, Prince, Jessica L., Gilmour, Jill, Hunter, Eric, Allen, Susan A., Claiborne, Daniel T., Altfeld, Marcus, Douek, Daniel

2019

Overview

Despite extensive research on the mechanisms of HLA-mediated immune control of HIV-1 pathogenesis, it is clear that much remains to be discovered, as exemplified by protective HLA alleles like HLA-B*81 which are associated with profound protection from CD4+ T cell decline without robust control of early plasma viremia. Here, we report on additional HLA class I (B*1401, B*57, B*5801, as well as B*81), and HLA class II (DQB1*02 and DRB1*15) alleles that display discordant virological and immunological phenotypes in a Zambian early infection cohort. HLA class I alleles of this nature were also associated with enhanced immune responses to conserved epitopes in Gag. Furthermore, these HLA class I alleles were associated with reduced levels of lipopolysaccharide (LPS) in the plasma during acute infection. Elevated LPS levels measured early in infection predicted accelerated CD4+ T cell decline, as well as immune activation and exhaustion. Taken together, these data suggest novel mechanisms for HLA-mediated immune control of HIV-1 pathogenesis that do not necessarily involve significant control of early viremia and point to microbial translocation as a direct driver of HIV-1 pathogenesis rather than simply a consequence.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / AIDS / Alleles / Analysis / Antigenic determinants / Antiretroviral drugs / Biology and Life Sciences / CD4 antigen / CD4-Positive T-Lymphocytes - immunology / Cell activation / Cohort Studies / Development and progression / Drb1 protein / Epitopes / Exhaustion / Female / Gag protein / Genes, MHC Class I - genetics / Health aspects / Histocompatibility antigen HLA / HIV / HIV infections / HIV Infections - genetics / HIV Infections - immunology / HIV Infections - virology / HIV-1 - genetics / HIV-1 - immunology / HIV-1 - pathogenicity / HLA antigens / Human immunodeficiency virus / Humans / Immune response / Immunology / Infections / Laboratories / Lipopolysaccharides / Lipopolysaccharides - deficiency / Lymphocytes / Lymphocytes T / Male / Measurement / Medical research / Medicine and Health Sciences / Microorganisms / Mitogens / Novels / Pathogenesis / Phenotypes / Robust control / T cells / T-Lymphocytes, Cytotoxic - immunology / Translocation / Vaccines / Viral Load / Viremia / Virus diseases / Virus Replication - genetics / Virus Replication - immunology