Journal article
Weaker HLA footprints on HIV in the unique and highly genetically admixed host population of Mexico
Journal of Virology, Vol.92(2)
2017
Abstract
HIV circumvents HLA class I-restricted CD8+ T-cell responses through selection of escape mutations that leave characteristic mutational “footprints,” also known as HLA-associated polymorphisms (HAPs), on HIV sequences at the population level. While many HLA footprints are universal across HIV subtypes and human populations, others can be region specific as a result of the unique immunogenetic background of each host population. Using a published probabilistic phylogenetically informed model, we compared HAPs in HIV Gag and Pol (PR-RT) in 1,612 subtype B-infected, antiretroviral treatment-naive individuals from Mexico and 1,641 individuals from Canada/United States. A total of 252 HLA class I allele subtypes were represented, including 140 observed in both cohorts, 67 unique to Mexico, and 45 unique to Canada/United States. At the predefined statistical threshold of a q value of <0.2, 358 HAPs (201 in Gag, 157 in PR-RT) were identified in Mexico, while 905 (534 in Gag and 371 in PR-RT) were identified in Canada/United States. HAPs identified in Mexico included both canonical HLA-associated escape pathways and novel associations, in particular with HLA alleles enriched in Amerindian and mestizo populations. Remarkably, HLA footprints on HIV in Mexico were not only fewer but also, on average, significantly weaker than those in Canada/United States, although some exceptions were noted. Moreover, exploratory analyses suggested that the weaker HLA footprint on HIV in Mexico may be due, at least in part, to weaker and/or less reproducible HLA-mediated immune pressures on HIV in this population. The implications of these differences for natural and vaccine-induced anti-HIV immunity merit further investigation.
Details
- Title
- Weaker HLA footprints on HIV in the unique and highly genetically admixed host population of Mexico
- Authors/Creators
- M. Soto-Nava (Author/Creator) - aCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoS. Avila-Rios (Author/Creator) - aCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoH. Valenzuela-Ponce (Author/Creator) - aCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoC. Garcia-Morales (Author/Creator) - aCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoJ.M. Carlson (Author/Creator) - bMicrosoft Research, Redmond, Washington, USAD. Tapia-Trejo (Author/Creator) - aCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoD. Garrido-Rodriguez (Author/Creator) - aCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoS.N. Alva-Hernández (Author/Creator) - aCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoT.A. García-Tellez (Author/Creator) - aCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoA. Murakami-Ogasawara (Author/Creator) - aCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoS.A. Mallal (Author/Creator) - Murdoch UniversityM. John (Author/Creator) - Murdoch UniversityM.A. Brockman (Author/Creator) - Simon Fraser UniversityC.J. Brumme (Author/Creator) - AIDS VancouverZ.L. Brumme (Author/Creator) - Simon Fraser UniversityG. Reyes-Teran (Author/Creator) - aCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoG. Silvestri (Author/Creator)
- Publication Details
- Journal of Virology, Vol.92(2)
- Publisher
- American Society for Microbiology
- Identifiers
- 991005540376407891
- Copyright
- © 2018 by the American Society for Microbiology
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.46 HIV Pathogenesis
- Web Of Science research areas
- Virology
- ESI research areas
- Microbiology