Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1

PLoS Pathog. 2017 Nov 6;13(11):e1006703. doi: 10.1371/journal.ppat.1006703. eCollection 2017 Nov.


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.

MeSH terms

  • African Continental Ancestry Group
  • Antigens, CD / genetics*
  • Genetic Predisposition to Disease*
  • Genetic Variation / genetics
  • Genome-Wide Association Study
  • HIV Infections / genetics*
  • HIV Infections / transmission
  • HIV-1 / genetics
  • Humans
  • Membrane Glycoproteins / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Risk
  • Sexual Behavior
  • Transcription Factors / genetics*
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Whole Genome Sequencing*


  • Antigens, CD
  • CD101 antigen, human
  • Membrane Glycoproteins
  • Transcription Factors
  • UBE2V1 protein, human
  • Ubiquitin-Conjugating Enzymes

Associated data

  • ClinicalTrials.gov/NCT00194519
  • ClinicalTrials.gov/NCT00557245