دورية أكاديمية
Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1.
| العنوان: | Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1. |
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| المؤلفون: | Zabrina L Brumme, Chanson J Brumme, David Heckerman, Bette T Korber, Marcus Daniels, Jonathan Carlson, Carl Kadie, Tanmoy Bhattacharya, Celia Chui, James Szinger, Theresa Mo, Robert S Hogg, Julio S G Montaner, Nicole Frahm, Christian Brander, Bruce D Walker, P Richard Harrigan |
| المصدر: | PLoS Pathogens, Vol 3, Iss 7, p e94 (2007) |
| بيانات النشر: | Public Library of Science (PLoS), 2007. |
| سنة النشر: | 2007 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| Relation: | http://europepmc.org/articles/PMC1904471?pdf=render; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.0030094 |
| URL الوصول: | https://doaj.org/article/19de9ceb19fb40818ab5ac1b57c7dd0d |
| رقم الأكسشن: | edsdoj.19de9ceb19fb40818ab5ac1b57c7dd0d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.0030094 |