TY - JOUR
T1 - Human immunotypes impose selection on viral genotypes through viral epitope specificity
AU - Gabrielaite, Migle
AU - Bennedbæk, Marc
AU - Zucco, Adrian G
AU - Ekenberg, Christina
AU - Murray, Daniel D
AU - Kan, Virginia L
AU - Touloumi, Giota
AU - Vandekerckhove, Linos
AU - Turner, Dan
AU - Neaton, James
AU - Lane, H Clifford
AU - Safo, Sandra
AU - Arenas-Pinto, Alejandro
AU - Polizzotto, Mark N
AU - Günthard, Huldrych F
AU - Lundgren, Jens D
AU - Marvig, Rasmus L
AU - INSIGHT START trial group
N1 - © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].
PY - 2021/12/15
Y1 - 2021/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85123648462&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiab253
DO - 10.1093/infdis/jiab253
M3 - Journal article
C2 - 33974707
SN - 0022-1899
VL - 224
SP - 2053
EP - 2063
JO - The Journal of infectious diseases
JF - The Journal of infectious diseases
IS - 12
ER -