Human Immunotypes Impose Selection on Viral Genotypes Through Viral Epitope Specificity

Migle Gabrielaite, Marc Bennedbæk, Adrian G. Zucco, Christina Ekenberg, Daniel D. Murray, Virginia L. Kan, Giota Touloumi, Linos Vandekerckhove, Dan Turner, James Neaton, H. Clifford Lane, Sandra Safo, Alejandro Arenas-Pinto, Mark N. Polizzotto, Huldrych F. Günthard, Jens D. Lundgren, Rasmus L. Marvig

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Understanding the genetic interplay between human hosts and infectious pathogens is crucial for how we interpret virulence factors. Here, we tested for associations between HIV and host genetics, and interactive genetic effects on viral load (VL) in HIV-positive antiretroviral treatment-naive clinical trial participants. Methods: HIV genomes were sequenced and the encoded amino acid (AA) variants were associated with VL, human single nucleotide polymorphisms (SNPs), and imputed HLA alleles using generalized linear models with Bonferroni correction. Results: Human (388 501 SNPs) and HIV (3010 variants) genetic data were available for 2122 persons. Four HIV variants were associated with VL (P < 1.66 × 10-5). Twelve HIV variants were associated with a range of 1-512 human SNPs (P < 4.28 × 10-11). We found 46 associations between HLA alleles and HIV variants (P < 1.29 × 10-7). HIV variants and immunotypes when analyzed separately were associated with lower VL, whereas the opposite was true when analyzed in concert. Epitope binding predictions supported our observations. Conclusions: Our results show the importance of immunotype specificity on viral antigenic determinants, and the identified genetic interplay emphasizes that viral and human genetics should be studied in the context of each other. Clinical Trials Registration: NCT00867048.

Original languageEnglish
Pages (from-to)2053-2063
Number of pages11
JournalJournal of Infectious Diseases
Volume224
Issue number12
DOIs
StatePublished - 15 Dec 2021

Keywords

  • genome-to-genome analysis
  • genome-wide association study
  • GWAS
  • HIV
  • host genomics
  • viral genomics
  • viral load

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