Systematic screening of viral and human genetic variation identifies antiretroviral resistance and immune escape link.

Détails

ID Serval
serval:BIB_CDF338C143A7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Systematic screening of viral and human genetic variation identifies antiretroviral resistance and immune escape link.
Périodique
eLife
Auteur(s)
Nguyen H., Thorball C.W., Fellay J., Böni J., Yerly S., Perreau M., Hirsch H.H., Kusejko K., Thurnheer M.C., Battegay M., Cavassini M., Kahlert C.R., Bernasconi E., Günthard H.F., Kouyos R.D.
Collaborateur(s)
Swiss HIV Cohort Study
ISSN
2050-084X (Electronic)
ISSN-L
2050-084X
Statut éditorial
Publié
Date de publication
01/06/2021
Peer-reviewed
Oui
Volume
10
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Considering the remaining threat of drug-resistantmutations (DRMs) to antiretroviral treatment (ART) efficacy, we investigated how the selective pressure of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes drives certain DRMs' emergence and retention.
We systematically screened DRM:HLA class I allele combinations in 3997 ART-naïve Swiss HIV Cohort Study (SHCS) patients. For each pair, a logistic regression model preliminarily tested for an association with the DRM as the outcome. The three HLA:DRM pairs remaining after multiple testing adjustment were analyzed in three ways: cross-sectional logistic regression models to determine any HLA/infection time interaction, survival analyses to examine if HLA type correlated with developing specific DRMs, and via NetMHCpan to find epitope binding evidence of immune escape.
Only one pair, RT-E138:HLA-B18, exhibited a significant interaction between infection duration and HLA. The survival analyses predicted two pairs with an increased hazard of developing DRMs: RT-E138:HLA-B18 and RT-V179:HLA-B35. RT-E138:HLA-B18 exhibited the greatest significance in both analyses (interaction term odds ratio [OR] 1.169 [95% confidence interval (CI) 1.075-1.273]; p-value<0.001; survival hazard ratio 12.211 [95% CI 3.523-42.318]; p-value<0.001). The same two pairs were also predicted by netMHCpan to have epitopic binding.
We identified DRM:HLA pairs where HLA presence is associated with the presence or emergence of the DRM, indicating that the selective pressure for these mutations alternates direction depending on the presence of these HLA alleles.
Funded by the Swiss National Science Foundation within the framework of the SHCS, and the University of Zurich, University Research Priority Program: Evolution in Action: From Genomes Ecosystems, in Switzerland.
Mots-clé
HIV, HLA, epidemiology, global health, human, infectious disease, microbiology, mutations
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/06/2021 14:30
Dernière modification de la notice
27/06/2021 6:37
Données d'usage