TY - JOUR
T1 - Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis
AU - Claiborne, Daniel T.
AU - Scully, Eileen P.
AU - Palmer, Christine D.
AU - Prince, Jessica L.
AU - MacHaria, Gladys N.
AU - Kopycinski, Jakub
AU - Michelo, Clive M.
AU - Wiener, Howard W.
AU - Parker, Rachel
AU - Nganou-Makamdop, Krystelle
AU - Douek, Daniel
AU - Altfeld, Marcus
AU - Gilmour, Jill
AU - Price, Matt A.
AU - Tang, Jianming
AU - Kilembe, William
AU - Allen, Susan A.
AU - Hunter, Eric
N1 - Publisher Copyright:
© 2019 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.ppat.1007981
DO - 10.1371/journal.ppat.1007981
M3 - Article
C2 - 31449552
AN - SCOPUS:85071829653
SN - 1553-7366
VL - 15
JO - PLoS pathogens
JF - PLoS pathogens
IS - 8
M1 - e1007981
ER -