Journal article
HLA-associated preadaptation in HIV Vif is associated with higher set point viral load and faster CD4+ decline in Zambian transmission pairs
AIDS (London), Vol.35(8), pp.1157-1165
07/01/2021
DOI: 10.1097/QAD.0000000000002868
PMCID: PMC8546905
PMID: 33710015
Abstract
Objective (s): We investigated the relationship between human leukocyte antigen (HLA)-associated preadaptation for the entire subtype C HIV-1 proteome of the transmitted founder virus and subsequent HIV-1 disease progression in a cohort of heterosexual linked transmission pairs in Zambia.
Design: An adaptation model was used to calculate an adaptation score for each virus-HLA combination in order to quantify the degree of preadaptation of the transmitted virus to the linked recipient's HLA alleles. These scores were then assessed for their relationship to viral load and longitudinal CD4(+) decline in the recipient.
Methods: Viral RNA was extracted from the plasma of the donor partner and the linked recipient near the time of transmission, as well as longitudinally from the linked recipient. Viral adaptation scores were calculated for each individual and each protein in the subtype C HIV-1 proteome.
Results: The majority of HLA-associated sites were located in Gag, Pol and Nef; however, proportional to protein length, the accessory and regulatory proteins contained a relatively high proportion of HLA-associated sites. Over the course of infection, HLA-mediated immune adaptation increased for all proteins except Vpu and gp120. Preadaptation was positively associated with higher early set point viral load and faster CD4(+) decline. When examined by protein, preadaptation in Pol and Vif were statistically significantly associated with these markers of disease progression.
Conclusion: Adaptation in Pol had the greatest impact on viral control. Despite containing a large proportion of HLA-associated sites, Vif was the only regulatory or accessory protein for which preadaptation significantly correlated with disease progression.
Details
- Title: Subtitle
- HLA-associated preadaptation in HIV Vif is associated with higher set point viral load and faster CD4+ decline in Zambian transmission pairs
- Creators
- Sarah Connolly - Emory UniversityJonathan M. Carlson - Microsoft (United States)Malinda Schaefer - Emory UniversityAlfred Bere - Emory UniversityWilliam Kilembe - Emory and Henry CollegeSusan Allen - Emory UniversityEric Hunter - Emory University
- Resource Type
- Journal article
- Publication Details
- AIDS (London), Vol.35(8), pp.1157-1165
- DOI
- 10.1097/QAD.0000000000002868
- PMID
- 33710015
- PMCID
- PMC8546905
- NLM abbreviation
- AIDS
- ISSN
- 0269-9370
- eISSN
- 1473-5571
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 9
- Grant note
- Norwegian Agency for Development Cooperation (NORAD); Norwegian Agency for Development Cooperation - NORAD P51OD11132 / Yerkes National Primate Research Center base grant through the Office of Research Infrastructure Programs/OD Ministry of Foreign Affairs of the Netherlands United States Agency for International Development (USAID); CGIAR; Norwegian Agency for Development Cooperation - NORAD Ministry of Foreign Affairs of Denmark P30 AI050409 / Virology Core at the Emory Center for AIDS Research Bill & Melinda Gates Foundation; Bill & Melinda Gates Foundation Grand Challenges Explorations Initiative; CGIAR IAVI Irish Aid; CGIAR Ministry of Finance of Japan United Kingdom Department for International Development (DFID)
- Language
- English
- Date published
- 07/01/2021
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984696762402771
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