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Rigshospitalet - a part of Copenhagen University Hospital
E-pub ahead of print

Human immunotypes impose selection on viral genotypes through viral epitope specificity

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

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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+ ART-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 (3,010 variants) genetic data was available for 2,122 persons. Four HIV variants were associated with VL (p-values<1.66×10 -5). Twelve HIV variants were associated with a range of 1-512 human SNPs (p-value<4.28×10 -11). We found 46 associations between HLA alleles and HIV variants (p-values<1.29×10 -7). We found HIV variants and immunotypes when analyzed separately, were associated with lower VL, whereas the opposite was true when analyzed in concert. Epitope binding prediction showed HLA alleles to be weaker binders of associated HIV AA variants relative to alternative variants on the same position.

CONCLUSIONS: Our results show the importance of immunotype specificity on viral antigenic determinants, and the identified genetic interplay puts emphasis that viral and human genetics should be studied in the context of each other.

Original languageEnglish
JournalThe Journal of infectious diseases
ISSN0022-1899
DOIs
Publication statusE-pub ahead of print - 11 May 2021

ID: 65482963