Journal article
Balance between transmitted HLA preadapted and nonassociated polymorphisms is a major determinant of HIV-1 disease progression
The Journal of experimental medicine, Vol.213(10), pp.2049-2063
09/19/2016
DOI: 10.1084/jem.20151984
PMCID: PMC5030801
PMID: 27551154
Abstract
HIV-1 adapts to a new host through mutations that facilitate immune escape. Here, we evaluate the impact on viral control and disease progression of transmitted polymorphisms that were either preadapted to or nonassociated with the new host's HLA. In a cohort of 169 Zambian heterosexual transmission pairs, we found that almost one-third of possible HLA-linked target sites in the transmitted virus Gag protein are already adapted, and that this transmitted preadaptation significantly reduced early immune recognition of epitopes. Transmitted preadapted and nonassociated polymorphisms showed opposing effects on set-point VL and the balance between the two was significantly associated with higher set-point VLs in a multivariable model including other risk factors. Transmitted preadaptation was also significantly associated with faster CD4 decline (<350 cells/µl) and this association was stronger after accounting for nonassociated polymorphisms, which were linked with slower CD4 decline. Overall, the relative ratio of the two classes of polymorphisms was found to be the major determinant of CD4 decline in a multivariable model including other risk factors. This study reveals that, even before an immune response is mounted in the new host, the balance of these opposing factors can significantly influence the outcome of HIV-1 infection.
Details
- Title: Subtitle
- Balance between transmitted HLA preadapted and nonassociated polymorphisms is a major determinant of HIV-1 disease progression
- Creators
- Daniela C Mónaco - Emory UniversityDario A Dilernia - Emory UniversityAndrew Fiore-Gartland - Fred Hutch Cancer CenterTianwei Yu - Emory UniversityJessica L Prince - Emory UniversityKristine K Dennis - Emory UniversityKai Qin - University of Alabama at BirminghamMalinda Schaefer - Emory UniversityDaniel T Claiborne - Emory UniversityWilliam Kilembe - Emory and Henry CollegeJianming Tang - University of Alabama at BirminghamMatt A Price - University of California, San FranciscoPaul Farmer - Emory UniversityJill Gilmour - IAVI, London SW10 9NH, England, UKAnju Bansal - University of Alabama at BirminghamSusan Allen - Emory UniversityPaul Goepfert - University of Alabama at BirminghamEric Hunter - Emory University
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.213(10), pp.2049-2063
- DOI
- 10.1084/jem.20151984
- PMID
- 27551154
- PMCID
- PMC5030801
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Grant note
- R37 AI051231 / NIAID NIH HHS R01 AI064060 / NIAID NIH HHS P30 AI050409 / NIAID NIH HHS P51 RR000165 / NCRR NIH HHS UM1 AI068635 / NIAID NIH HHS P51 OD011132 / NIH HHS R01 AI112566 / NIAID NIH HHS
- Language
- English
- Date published
- 09/19/2016
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984697044002771
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