Year: 2019
Type: article
Abstract: BACKGROUND: HIV's capacity to escape immune recognition by human leukocyte antigen (HLA) is a core component of HIV pathogenesis. A better understanding of the distribution of HLA class I in HIV-infected patients would improve our knowledge of pathogenesis in relation to the host HLA type and could better improve therapeutic strategies against HIV. MATERIALS AND METHODS: Three hundred one to 325 transmission pairs and 469-496 clusters were identified for analysis among Swiss HIV Cohort Study (SHCS) participants using HIV pol sequences from the drug resistance database. HLA class I data were compiled at 3 specificity levels: 4-digit, 2-digit alleles, and HLA-B supertype. The analysis tabulated HLA-I homogeneity as 2 measures: the proportion of transmission pairs, which are HLA concordant, and the average percentage of allele matches within all clusters. These measures were compared with the mean value across randomizations with randomly assorted individuals. RESULTS: We repeated the analysis for different HLA classification levels and separately for HLA-A, -B, and -C. Subanalyses by the risk group were performed for HLA-B. HLA-B showed significantly greater homogeneity in the transmission chains (2-digit clusters: 0.291 vs. 0.251, P value = 0.009; supertype clusters: 0.659 vs. 0.611, P value = 0.002; supertype pairs: 0.655 vs. 0.608, P value = 0.014). Risk group restriction caused the effect to disappear for men-who-have-sex-with-men but not for other risk groups. We also examined if protective HLA alleles B27 and B57 were under- or overrepresented in the transmission chains, although this yielded no significant pattern. CONCLUSIONS: The HLA-B alleles of patients within HIV-1 transmission chains segregate in homogenous clusters/pairs, potentially indicating preferential transmission among HLA-B concordant individuals.
Authors: Huyen Nguyen, Christian W. Thorball, Jacques Fellay, Jürg Böni, Sabine Yerly, Matthieu Perreau, Thomas Klimkait, Katharina Kusejko, Nadine Bachmann, Sandra E. Chaudron, Paolo Paioni, Maria C. Thurnheer, Manuel Battegay, Matthias Cavassini, Pietro Vernazza, Enos Bernasconi, Huldrych F. Günthard, Roger Kouyos, the Swiss HIV Cohort Study
Institutions: University of Zurich, University Hospital Zurich, SIB Swiss Institute of Bioinformatics, École Polytechnique Fédérale de Lausanne, University of Geneva, University Hospital of Geneva, Centre Hospitalier Universitaire Vaudois, University of Lausanne, University of Basel, University Children's Hospital Zurich, University of Bern, University Hospital of Bern, University Hospital of Basel, Kantonsspital St. Gallen, Ospedale regionale di Lugano
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2945808168