Τίτλος:
Human Immunotypes Impose Selection on Viral Genotypes Through Viral Epitope Specificity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2021 The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Συγγραφείς:
Gabrielaite, M.
Bennedbæk, M.
Zucco, A.G.
Ekenberg, C.
Murray, D.D.
Kan, V.L.
Touloumi, G.
Vandekerckhove, L.
Turner, D.
Neaton, J.
Clifford Lane, H.
Safo, S.
Arenas-Pinto, A.
Polizzotto, M.N.
Günthard, H.F.
Lundgren, J.D.
Marvig, R.L.
Περιοδικό:
JOURNAL OF INFECTIOUS DISEASES
Εκδότης:
Oxford University Press
Λέξεις-κλειδιά:
epitope, adult; female; genetics; genome-wide association study; genotype; human; human genome; Human immunodeficiency virus 1; Human immunodeficiency virus infection; immunology; male; middle aged; single nucleotide polymorphism; virology; virus genome; virus load, Adult; Epitopes; Female; Genome, Human; Genome, Viral; Genome-Wide Association Study; Genotype; HIV Infections; HIV-1; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Viral Load
DOI:
10.1093/infdis/jiab253
