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Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1

PLoS pathogens, 2007-07, Vol.3 (7), p.e94 [Peer Reviewed Journal]

COPYRIGHT 2007 Public Library of Science ;2007 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Brumme ZL, Brumme CJ, Heckerman D, Korber BT, Daniels M, et al. (2007) Evidence of Differential HLA Class I-Mediated Viral Evolution in Functional and Accessory/Regulatory Genes of HIV-1. PLoS Pathog 3(7): e94. doi:10.1371/journal.ppat.0030094 ;This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. 2007 ;2007 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Brumme ZL, Brumme CJ, Heckerman D, Korber BT, Daniels M, et al. (2007) Evidence of Differential HLA Class I-Mediated Viral Evolution in Functional and Accessory/Regulatory Genes of HIV-1. PLoS Pathog 3(7): e94. doi:10.1371/journal.ppat.0030094 ;ISSN: 1553-7374 ;ISSN: 1553-7366 ;EISSN: 1553-7374 ;DOI: 10.1371/journal.ppat.0030094 ;PMID: 17616974

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Title:
Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1
Author: Brumme, Zabrina L ; Brumme, Chanson J ; Heckerman, David ; Korber, Bette T ; Daniels, Marcus ; Carlson, Jonathan ; Kadie, Carl ; Bhattacharya, Tanmoy ; Chui, Celia ; Szinger, James ; Mo, Theresa ; Hogg, Robert S ; Montaner, Julio S G ; Frahm, Nicole ; Brander, Christian ; Walker, Bruce D ; Harrigan, P Richard
Koup, Richard A
Subjects: alleles ; Amino Acid Sequence ; BASIC BIOLOGICAL SCIENCES ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; epitope mapping ; Epitopes, T-Lymphocyte - genetics ; Epitopes, T-Lymphocyte - immunology ; Evolution ; Evolution, Molecular ; Gene Expression Regulation, Viral ; Genes ; Genes, MHC Class I - physiology ; Genetic aspects ; Histocompatibility Antigens Class I - genetics ; HIV ; HIV (Viruses) ; HIV-1 ; HIV-1 - genetics ; HIV-1 - immunology ; Human Immunodeficiency Virus Proteins - genetics ; Human Immunodeficiency Virus Proteins - metabolism ; Humans ; Immunology ; Medical research ; microbial mutation ; Minor Histocompatibility Antigens ; Molecular evolution ; Molecular Sequence Data ; Mutation ; nef Gene Products, Human Immunodeficiency Virus - genetics ; nef Gene Products, Human Immunodeficiency Virus - metabolism ; Phylogeny ; Polymorphism, Genetic ; proteases ; protein sequencing ; Selection, Genetic ; Studies ; Viral genetics ; Viral Regulatory and Accessory Proteins - genetics ; Viral Regulatory and Accessory Proteins - metabolism ; Virology ; Viruses ; vpr Gene Products, Human Immunodeficiency Virus - genetics ; vpr Gene Products, Human Immunodeficiency Virus - metabolism
Is Part Of: PLoS pathogens, 2007-07, Vol.3 (7), p.e94
Description: Despite the formidable mutational capacity and sequence diversity of HIV-1, evidence suggests that viral evolution in response to specific selective pressures follows generally predictable mutational pathways. Population-based analyses of clinically derived HIV sequences may be used to identify immune escape mutations in viral genes; however, prior attempts to identify such mutations have been complicated by the inability to discriminate active immune selection from virus founder effects. Furthermore, the association between mutations arising under in vivo immune selection and disease progression for highly variable pathogens such as HIV-1 remains incompletely understood. We applied a viral lineage-corrected analytical method to investigate HLA class I-associated sequence imprinting in HIV protease, reverse transcriptase (RT), Vpr, and Nef in a large cohort of chronically infected, antiretrovirally naïve individuals. A total of 478 unique HLA-associated polymorphisms were observed and organized into a series of "escape maps," which identify known and putative cytotoxic T lymphocyte (CTL) epitopes under selection pressure in vivo. Our data indicate that pathways to immune escape are predictable based on host HLA class I profile, and that epitope anchor residues are not the preferred sites of CTL escape. Results reveal differential contributions of immune imprinting to viral gene diversity, with Nef exhibiting far greater evidence for HLA class I-mediated selection compared to other genes. Moreover, these data reveal a significant, dose-dependent inverse correlation between HLA-associated polymorphisms and HIV disease stage as estimated by CD4(+) T cell count. Identification of specific sites and patterns of HLA-associated polymorphisms across HIV protease, RT, Vpr, and Nef illuminates regions of the genes encoding these products under active immune selection pressure in vivo. The high density of HLA-associated polymorphisms in Nef compared to other genes investigated indicates differential HLA class I-driven evolution in different viral genes. The relationship between HLA class I-associated polymorphisms and lower CD4(+) cell count suggests that immune escape correlates with disease status, supporting an essential role of maintenance of effective CTL responses in immune control of HIV-1. The design of preventative and therapeutic CTL-based vaccine approaches could incorporate information on predictable escape pathways.
Publisher: United States: Public Library of Science
Language: English
Identifier: ISSN: 1553-7374
ISSN: 1553-7366
EISSN: 1553-7374
DOI: 10.1371/journal.ppat.0030094
PMID: 17616974
Source: PLoS (Open access)
PubMed Central (Open access)
Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
Directory of Open Access Journals
ProQuest Central

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Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1

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