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

Academic Article

Abstract

  • 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.
  • Published In

  • PLoS Pathogens  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 27550065
  • Author List

  • Claiborne DT; Scully EP; Palmer CD; Prince JL; MacHaria GN; Kopycinski J; Michelo CM; Wiener HW; Parker R; Nganou-Makamdop K
  • Volume

  • 15
  • Issue

  • 8