دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis.
المؤلفون: Claiborne DT; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America., Scully EP; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America., Palmer CD; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America., Prince JL; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America., Macharia GN; Human Immunology Laboratory, International AIDS Vaccine Initiative, London, United Kingdom., Kopycinski J; Human Immunology Laboratory, International AIDS Vaccine Initiative, London, United Kingdom., Michelo CM; Zambia-Emory HIV Research Project, Lusaka, Zambia., Wiener HW; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America., Parker R; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America., Nganou-Makamdop K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America., Douek D; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America., Altfeld M; Virus Immunology Unit, Heinrich-Pette-Institut, Hamburg, Germany., Gilmour J; Human Immunology Laboratory, International AIDS Vaccine Initiative, London, United Kingdom., Price MA; International AIDS Vaccine Initiative, New York, New York, United States of America.; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California, United States of America., Tang J; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America., Kilembe W; Zambia-Emory HIV Research Project, Lusaka, Zambia., Allen SA; Zambia-Emory HIV Research Project, Lusaka, Zambia.; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America., Hunter E; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America.
المصدر: PLoS pathogens [PLoS Pathog] 2019 Aug 26; Vol. 15 (8), pp. e1007981. Date of Electronic Publication: 2019 Aug 26 (Print Publication: 2019).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: CD4-Positive T-Lymphocytes/*immunology , Genes, MHC Class I/*genetics , HIV Infections/*immunology , HIV-1/*immunology , HIV-1/*pathogenicity , Lipopolysaccharides/*deficiency , Virus Replication/*immunology, Alleles ; Cohort Studies ; Female ; HIV Infections/genetics ; HIV Infections/virology ; HIV-1/genetics ; Humans ; Male ; T-Lymphocytes, Cytotoxic/immunology ; Viral Load ; Virus Replication/genetics
مستخلص: 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.
Competing Interests: The authors have declared that no competing interests exist.
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معلومات مُعتمدة: P30 AI050409 United States AI NIAID NIH HHS; P51 OD011132 United States OD NIH HHS; R01 AI051231 United States AI NIAID NIH HHS; F32 AI136750 United States AI NIAID NIH HHS; K08 AI116344 United States AI NIAID NIH HHS; R01 AI064060 United States AI NIAID NIH HHS; R01 MH095503 United States MH NIMH NIH HHS
المشرفين على المادة: 0 (Lipopolysaccharides)
تواريخ الأحداث: Date Created: 20190827 Date Completed: 20200115 Latest Revision: 20201213
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6730937
DOI: 10.1371/journal.ppat.1007981
PMID: 31449552
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1007981