Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1
Year: 2017
Type: article
Study design: Observational Study
Abstract: Host genetic variation modifying HIV-1 acquisition risk can inform development of HIV-1 prevention strategies. However, associations between rare or intermediate-frequency variants and HIV-1 acquisition are not well studied. We tested for the association between variation in genic regions and extreme HIV-1 acquisition phenotypes in 100 sub-Saharan Africans with whole genome sequencing data. Missense variants in immunoglobulin-like regions of CD101 and, among women, one missense/5' UTR variant in UBE2V1, were associated with increased HIV-1 acquisition risk (p = 1.9x10-4 and p = 3.7x10-3, respectively, for replication). Both of these genes are known to impact host inflammatory pathways. Effect sizes increased with exposure to HIV-1 after adjusting for the independent effect of increasing exposure on acquisition risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT00194519; NCT00557245.
Source: PLoS Pathogens
Authors: Romel D. Mackelprang, Michael J. Bamshad, Jessica X. Chong, Xuanlin Hou, Kati J. Buckingham, Kathryn Shively, Guy deBruyn, Nelly R. Mugo, James I. Mullins, M. Juliana McElrath, Jared M. Baeten, Connie Celum, Mary J. Emond, Jairam R. Lingappa, for the Partners in Prevention HSV/HIV Transmission Study and the Partners PrEP Study Teams
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Awards: G1088475248, G2121068341, Complete Genome Variation in Africans with Extreme HIV-1 Transmission Phenotypes, G2219438539, G4393346530, G4941764901, G5806381717, G6625095162, G7335502968, G7791962275, CD101 function, T regulatory cells and HIV-1 acquisition risk, G9000186388, University of Washington/Fred Hutch Center for AIDS Research
OpenAlex ID: W2768025743