{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:41:56Z","timestamp":1788572516339,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012359","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000}}],"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1148284"],"award-info":[{"award-number":["APP1148284"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health-funded Tennessee Center for AIDS Research","award":["P30AI110527"],"award-info":[{"award-number":["P30AI110527"]}]},{"DOI":"10.13039\/501100001801","name":"University of Western Australia","doi-asserted-by":"publisher","award":["2022\/GR000787"],"award-info":[{"award-number":["2022\/GR000787"]}],"id":[{"id":"10.13039\/501100001801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011025","name":"Government of Western Australia","doi-asserted-by":"publisher","award":["2021\/GR000223"],"award-info":[{"award-number":["2021\/GR000223"]}],"id":[{"id":"10.13039\/501100011025","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BioZone"},{"name":"BioZone","award":["Completion Scholarship"],"award-info":[{"award-number":["Completion Scholarship"]}]},{"name":"Australian Government Research Training Program"},{"name":"Australian Government Research Training Program Fees Offset"},{"name":"The Swiss National Science Foundation","award":["201369"],"award-info":[{"award-number":["201369"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    A strong genetic predictor of outcome following untreated HIV-1 infection is the carriage of specific alleles of human leukocyte antigens (HLAs) that present viral epitopes to T cells. Residual variation in outcome measures may be attributed, in part, to viral adaptation to HLA-restricted T cell responses. Variants of the endoplasmic reticulum aminopeptidases (ERAPs) influence the repertoire of T cell epitopes presented by HLA alleles as they trim pathogen-derived peptide precursors to optimal lengths for antigen presentation, along with other functions unrelated to antigen presentation. We investigated whether ERAP variants influence HLA-associated HIV-1 adaptation with demonstrable effects on overall HIV-1 disease outcome. Utilizing host and viral data of 249 West Australian individuals with HIV-1 subtype B infection, we identified a novel association between two linked\n                    <jats:italic>ERAP2<\/jats:italic>\n                    single nucleotide polymorphisms (SNPs; rs2248374 and rs2549782) with plasma HIV RNA concentration (viral load) (P adjusted = 0.0024 for both SNPs). Greater HLA-associated HIV-1 adaptation in the HIV-1\n                    <jats:italic>Gag<\/jats:italic>\n                    gene correlated significantly with higher viral load, lower CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell count and proportion; P = 0.0103, P = 0.0061, P = 0.0061, respectively). When considered together, there was a significant interaction between the two\n                    <jats:italic>ERAP2<\/jats:italic>\n                    SNPs and HLA-associated HIV-1 adaptation on viral load (P = 0.0111). In a comprehensive multivariate model, addition of\n                    <jats:italic>ERAP2<\/jats:italic>\n                    haplotypes and HLA associated adaptation as an interaction term to known HLA and CCR5 determinants and demographic factors, increased the explanatory variance of population viral load from 17.67% to 45.1% in this dataset. These effects were not replicated in publicly available datasets with comparably sized cohorts, suggesting that any true global epistasis may be dependent on specific HLA-ERAP allelic combinations. Our data raises the possibility that\n                    <jats:italic>ERAP2<\/jats:italic>\n                    variants may shape peptide repertoires presented to HLA class I-restricted T cells to modulate the degree of viral adaptation within individuals, in turn contributing to disease variability at the population level. Analyses of other populations and experimental studies, ideally with locally derived ERAP genotyping and HLA-specific viral adaptations are needed to elucidate this further.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012359","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T14:33:32Z","timestamp":1720535612000},"page":"e1012359","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Epistatic interaction between ERAP2 and HLA modulates HIV-1 adaptation and disease outcome in an Australian population"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4228-8765","authenticated-orcid":true,"given":"Marwah","family":"Al-kaabi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Firth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Pavlos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abha","family":"Chopra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed","family":"Basiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Currenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyros","family":"Kalams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Fellay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Mallal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6873-0198","authenticated-orcid":true,"given":"Silvana","family":"Gaudieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"issue":"4","key":"ppat.1012359.ref001","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1073\/pnas.1119675109","article-title":"The mystery of missing heritability: Genetic interactions create phantom heritability","volume":"109","author":"O Zuk","year":"2012","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"12","key":"ppat.1012359.ref002","doi-asserted-by":"crossref","first-page":"e1000791","DOI":"10.1371\/journal.pgen.1000791","article-title":"Common genetic variation and the control of HIV-1 in humans.","volume":"5","author":"J Fellay","year":"2009","journal-title":"PLoS Genet"},{"issue":"6010","key":"ppat.1012359.ref003","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1126\/science.1195271","article-title":"The major genetic determinants of HIV-1 control affect HLA class I peptide presentation","volume":"330","author":"F Pereyra","year":"2010","journal-title":"Science"},{"issue":"47","key":"ppat.1012359.ref004","doi-asserted-by":"crossref","first-page":"14658","DOI":"10.1073\/pnas.1514867112","article-title":"Polymorphisms of large effect explain the majority of the host 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Kemming","year":"2019","journal-title":"J Hepatol"},{"issue":"32","key":"ppat.1012359.ref010","doi-asserted-by":"crossref","first-page":"30050","DOI":"10.1074\/jbc.M103177200","article-title":"A role for a novel luminal endoplasmic reticulum aminopeptidase in final trimming of 26 S proteasome-generated major histocompatability complex class I antigenic peptides","volume":"276","author":"A Komlosh","year":"2001","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1012359.ref011","doi-asserted-by":"crossref","first-page":"28902","DOI":"10.1038\/srep28902","article-title":"ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing","volume":"6","author":"H Chen","year":"2016","journal-title":"Scientific Reports"},{"issue":"6","key":"ppat.1012359.ref012","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.4049\/jimmunol.0903712","article-title":"Endoplasmic reticulum aminopeptidase associated with antigen processing defines the 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Services"},{"issue":"8","key":"ppat.1012359.ref024","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/sj.gene.6364256","article-title":"Killer immunoglobulin-like receptors and HLA act both independently and synergistically to modify HIV disease progression","volume":"6","author":"S Gaudieri","year":"2005","journal-title":"Genes Immun"},{"issue":"10","key":"ppat.1012359.ref025","doi-asserted-by":"crossref","first-page":"e1001157","DOI":"10.1371\/journal.pgen.1001157","article-title":"Balancing selection maintains a form of ERAP2 that undergoes nonsense-mediated decay and affects antigen presentation.","volume":"6","author":"AM Andr\u00e9s","year":"2010","journal-title":"PLoS Genet"},{"issue":"5","key":"ppat.1012359.ref026","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.4049\/jimmunol.1200918","article-title":"A common single nucleotide polymorphism in endoplasmic reticulum aminopeptidase 2 induces a specificity switch that leads to altered antigen processing","volume":"189","author":"I Evnouchidou","year":"2012","journal-title":"J Immunol"},{"issue":"4","key":"ppat.1012359.ref027","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/BOR.0000000000000189","article-title":"Endoplasmic reticulum-associated amino-peptidase 1 and rheumatic disease: genetics","volume":"27","author":"MJ Ombrello","year":"2015","journal-title":"Curr Opin Rheumatol"},{"key":"ppat.1012359.ref028","doi-asserted-by":"crossref","first-page":"566190","DOI":"10.3389\/fgene.2020.566190","article-title":"Polymorphisms in ERAP1 and ERAP2 Genes Are Associated With Tuberculosis in the Han Chinese.","volume":"11","author":"S Zhang","year":"2020","journal-title":"Front Genet"},{"issue":"3","key":"ppat.1012359.ref029","doi-asserted-by":"crossref","DOI":"10.3390\/cells9030720","article-title":"An Overview on ERAP Roles in Infectious Diseases.","volume":"9","author":"I Saulle","year":"2020","journal-title":"Cells"},{"issue":"7","key":"ppat.1012359.ref030","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1084\/jem.20031982","article-title":"Immune selection for altered antigen processing leads to cytotoxic T lymphocyte escape in chronic HIV-1 infection","volume":"199","author":"R Draenert","year":"2004","journal-title":"J Exp Med"},{"issue":"24","key":"ppat.1012359.ref031","doi-asserted-by":"crossref","first-page":"13202","DOI":"10.1128\/JVI.01998-12","article-title":"Correlates of protective cellular immunity revealed by analysis of population-level immune escape pathways in HIV-1","volume":"86","author":"JM Carlson","year":"2012","journal-title":"Journal of virology"},{"issue":"1","key":"ppat.1012359.ref032","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nm1520","article-title":"CD8+ T-cell responses to different HIV proteins have discordant associations with viral load","volume":"13","author":"P Kiepiela","year":"2007","journal-title":"Nature Medicine"},{"issue":"W1","key":"ppat.1012359.ref033","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data","volume":"48","author":"B Reynisson","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"ppat.1012359.ref034","doi-asserted-by":"crossref","first-page":"e1001341","DOI":"10.1371\/journal.ppat.1001341","article-title":"The antiviral efficacy of HIV-specific CD8+ T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate.","volume":"7","author":"SR Ranasinghe","year":"2011","journal-title":"PLoS Pathog."},{"issue":"7","key":"ppat.1012359.ref035","doi-asserted-by":"crossref","first-page":"4618","DOI":"10.4049\/jimmunol.175.7.4618","article-title":"CD8+ T cell epitope-flanking mutations disrupt proteasomal processing of HIV-1 Nef","volume":"175","author":"A Milicic","year":"2005","journal-title":"J Immunol"},{"key":"ppat.1012359.ref036","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.746986","article-title":"Cross-Reactivity to Mutated Viral Immune Targets Can Influence CD8+ T Cell Functionality: An Alternative Viral Adaptation Strategy.","volume":"12","author":"J Currenti","year":"2021","journal-title":"Frontiers in Immunology"},{"issue":"8","key":"ppat.1012359.ref037","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1128\/JVI.06000-11","article-title":"Antiretroviral Therapy Reduces the Magnitude and T Cell Receptor Repertoire Diversity of HIV-Specific T Cell Responses without Changing T Cell Clonotype Dominance","volume":"86","author":"JA Conrad","year":"2012","journal-title":"Journal of Virology"},{"issue":"21","key":"ppat.1012359.ref038","doi-asserted-by":"crossref","first-page":"10418","DOI":"10.1128\/JVI.01190-08","article-title":"Enhancement of human immunodeficiency virus (HIV)-specific CD8+ T cells in cerebrospinal fluid compared to those in blood among antiretroviral therapy-naive HIV-positive subjects.","volume":"82","author":"S Sadagopal","year":"2008","journal-title":"J Virol"},{"issue":"7976","key":"ppat.1012359.ref039","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/s41586-023-06370-4","article-title":"Africa-specific human genetic variation near CHD1L associates with HIV-1 load","volume":"620","author":"PJ McLaren","year":"2023","journal-title":"Nature"},{"key":"ppat.1012359.ref040","doi-asserted-by":"crossref","first-page":"e01123","DOI":"10.7554\/eLife.01123","article-title":"A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.","volume":"2","author":"I Bartha","year":"2013","journal-title":"eLife"},{"issue":"2","key":"ppat.1012359.ref041","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/tpj.2013.18","article-title":"HIBAG\u2014HLA genotype imputation with attribute bagging","volume":"14","author":"X Zheng","year":"2014","journal-title":"Pharmacogenomics J"},{"issue":"1","key":"ppat.1012359.ref042","first-page":"535","volume":"54","author":"O Carrington M","year":"2003","journal-title":"Brien SJ. The Influence of HLA Genotype on AIDS. Annual Review of Medicine"},{"key":"ppat.1012359.ref043","doi-asserted-by":"crossref","first-page":"778103","DOI":"10.3389\/fimmu.2021.778103","article-title":"ERAP1 Controls the Interaction of the Inhibitory Receptor KIR3DL1 With HLA-B51:01 by Affecting Natural Killer Cell Function.","volume":"12","author":"S D\u2019Amico","year":"2021","journal-title":"Front Immunol."},{"issue":"6","key":"ppat.1012359.ref044","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/ni.1728","article-title":"Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance","volume":"10","author":"S Tenzer","year":"2009","journal-title":"Nature Immunology"},{"issue":"11","key":"ppat.1012359.ref045","doi-asserted-by":"crossref","first-page":"e3658","DOI":"10.1371\/journal.pone.0003658","article-title":"The internal sequence of the peptide-substrate determines its N-terminus trimming by ERAP1.","volume":"3","author":"I Evnouchidou","year":"2008","journal-title":"PLoS One"},{"issue":"22","key":"ppat.1012359.ref046","doi-asserted-by":"crossref","first-page":"6081","DOI":"10.1093\/hmg\/ddu307","article-title":"A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy","volume":"23","author":"JJ Kuiper","year":"2014","journal-title":"Hum Mol Genet"},{"issue":"12","key":"ppat.1012359.ref047","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1101\/gr.240390.118","article-title":"Genetic analysis of isoform usage in the human anti-viral response reveals influenza-specific regulation of ERAP2 transcripts under balancing selection","volume":"28","author":"CJ Ye","year":"2018","journal-title":"Genome Res"},{"issue":"2","key":"ppat.1012359.ref048","doi-asserted-by":"crossref","first-page":"901","DOI":"10.4049\/jimmunol.1302855","article-title":"ERAP1-ERAP2 dimerization increases peptide-trimming efficiency","volume":"193","author":"I Evnouchidou","year":"2014","journal-title":"J Immunol"},{"issue":"7","key":"ppat.1012359.ref049","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/ni1208","article-title":"Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum","volume":"6","author":"L Saveanu","year":"2005","journal-title":"Nat Immunol"},{"key":"ppat.1012359.ref050","doi-asserted-by":"crossref","first-page":"902567","DOI":"10.3389\/fimmu.2022.902567","article-title":"To Be or Not to Be: The Case of Endoplasmic Reticulum Aminopeptidase 2.","volume":"13","author":"P. Ku\u015bnierczyk","year":"2022","journal-title":"Front Immunol."},{"issue":"11\u201312","key":"ppat.1012359.ref051","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.humimm.2017.10.005","article-title":"The ERAP gene is associated with HCV chronic infection in a Chinese Han population","volume":"78","author":"S Liu","year":"2017","journal-title":"Hum Immunol"},{"issue":"23","key":"ppat.1012359.ref052","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1093\/hmg\/ddq401","article-title":"Genetic diversity at endoplasmic reticulum aminopeptidases is maintained by balancing selection and is associated with natural resistance to HIV-1 infection","volume":"19","author":"R Cagliani","year":"2010","journal-title":"Hum Mol Genet"},{"issue":"11","key":"ppat.1012359.ref053","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1097\/QAD.0b013e3283601cee","article-title":"Endoplasmic reticulum aminopeptidase 2 haplotypes play a role in modulating susceptibility to HIV 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Reviews Genetics"},{"key":"ppat.1012359.ref057","article-title":"Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2).","author":"A Raja","year":"2023","journal-title":"Genes & Immunity"},{"issue":"2","key":"ppat.1012359.ref058","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/mgg3.13","article-title":"A Novel ERAP2 Haplotype Structure in a Chilean Population: Implications for ERAP2 Protein Expression and Preeclampsia Risk.","volume":"1","author":"DL Vanhille","year":"2013","journal-title":"Mol Genet Genomic Med."},{"issue":"7571","key":"ppat.1012359.ref059","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"A Auton","year":"2015","journal-title":"Nature"},{"issue":"10","key":"ppat.1012359.ref060","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1002\/art.39734","article-title":"Functional Interaction of the Ankylosing Spondylitis-Associated Endoplasmic Reticulum Aminopeptidase 2 With the HLA-B*27 Peptidome in Human Cells.","volume":"68","author":"A Mart\u00edn-Esteban","year":"2016","journal-title":"Arthritis Rheumatol."},{"issue":"11","key":"ppat.1012359.ref061","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1074\/mcp.RA119.001710","article-title":"Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis","volume":"18","author":"E Lorente","year":"2019","journal-title":"Mol Cell Proteomics"},{"key":"ppat.1012359.ref062","author":"S Leary","journal-title":"IIID VGAS\u2014A Visual Genome Analysis Studio incorporating high performance next generation sequence analysis2013."},{"issue":"6","key":"ppat.1012359.ref063","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1034\/j.1399-0039.2002.600602.x","article-title":"Common HLA-B8-DR3 haplotype in Northern India is different from that found in Europe","volume":"60","author":"CS Witt","year":"2002","journal-title":"Tissue Antigens"},{"key":"ppat.1012359.ref064","doi-asserted-by":"crossref","first-page":"497","DOI":"10.4236\/abb.2018.99034","article-title":"A High-Performing and Cost-Effective SNP Genotyping Method Using rhPCR and Universal Reporters","volume":"9","author":"K Beltz","year":"2018","journal-title":"Advances in Bioscience and Biotechnology"},{"key":"ppat.1012359.ref065","article-title":"haplo.stats: Statistical Analysis of Haplotypes with Traits and Covariates when Linkage Phase is Ambiguous","author":"JP Sinnwell","year":"2022","journal-title":"R package version 1.8.9."},{"issue":"3","key":"ppat.1012359.ref066","first-page":"799","article-title":"An E-M algorithm and testing strategy for multiple-locus haplotypes","volume":"56","author":"JC Long","year":"1995","journal-title":"Am J Hum Genet"},{"issue":"5","key":"ppat.1012359.ref067","first-page":"921","article-title":"Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population","volume":"12","author":"L Excoffier","year":"1995","journal-title":"Mol Biol Evol"},{"issue":"19","key":"ppat.1012359.ref068","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1093\/bioinformatics\/bti607","article-title":"An automated genotyping system for analysis of HIV-1 and other microbial sequences","volume":"21","author":"T de Oliveira","year":"2005","journal-title":"Bioinformatics"},{"issue":"18","key":"ppat.1012359.ref069","doi-asserted-by":"crossref","first-page":"e144","DOI":"10.1093\/nar\/gku739","article-title":"COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification","volume":"42","author":"D Struck","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"ppat.1012359.ref070","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms","volume":"35","author":"S Kumar","year":"2018","journal-title":"Mol Biol Evol"},{"issue":"2","key":"ppat.1012359.ref071","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/01.qai.0000223017.01568.e7","article-title":"Cross-clade reactivity of HIV-1-specific T-cell responses in HIV-1-infected individuals from Botswana and Cameroon.","volume":"42","author":"SB Gupta","year":"2006","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"17","key":"ppat.1012359.ref072","doi-asserted-by":"crossref","first-page":"11247","DOI":"10.1128\/JVI.79.17.11247-11258.2005","article-title":"Broad cross-clade T-cell responses to gag in individuals infected with human immunodeficiency virus type 1 non-B clades (A to G): importance of HLA anchor residue conservation.","volume":"79","author":"MJ Geels","year":"2005","journal-title":"J Virol"},{"issue":"40","key":"ppat.1012359.ref073","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.1016\/j.vaccine.2008.03.094","article-title":"Cross-clade immune responses to Gag p24 in patients infected with different HIV-1 subtypes and correlation with HLA class I and II alleles","volume":"26","author":"L Gudmundsdotter","year":"2008","journal-title":"Vaccine"},{"issue":"2","key":"ppat.1012359.ref074","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","article-title":"Haploview: analysis and visualization of LD and haplotype maps","volume":"21","author":"JC Barrett","year":"2005","journal-title":"Bioinformatics"},{"issue":"7","key":"ppat.1012359.ref075","doi-asserted-by":"crossref","first-page":"e1009131","DOI":"10.1371\/journal.pcbi.1009131","article-title":"MiDAS\u2014Meaningful Immunogenetic Data at Scale.","volume":"17","author":"M Migdal","year":"2021","journal-title":"PLOS Computational Biology"},{"issue":"5","key":"ppat.1012359.ref076","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1093\/bioinformatics\/btm025","article-title":"SNPassoc: an R package to perform whole genome association studies","volume":"23","author":"JR Gonz\u00e1lez","year":"2007","journal-title":"Bioinformatics"},{"issue":"5","key":"ppat.1012359.ref077","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1086\/429864","article-title":"A note on exact tests of Hardy-Weinberg equilibrium","volume":"76","author":"JE Wigginton","year":"2005","journal-title":"Am J Hum Genet"},{"issue":"6186","key":"ppat.1012359.ref078","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/335167a0","article-title":"Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection","volume":"335","author":"AL Hughes","year":"1988","journal-title":"Nature"},{"issue":"2","key":"ppat.1012359.ref079","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.2517-6161.1964.tb00553.x","article-title":"An Analysis of Transformations","volume":"26","author":"GEP Box","year":"1964","journal-title":"Journal of the Royal Statistical Society: Series B (Methodological)."},{"issue":"3","key":"ppat.1012359.ref080","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/00126334-200007010-00004","article-title":"Association of race and gender with HIV-1 RNA levels and immunologic progression","volume":"24","author":"K Anastos","year":"2000","journal-title":"J Acquir Immune Defic Syndr"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012359","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000}}],"container-title":["PLOS 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