{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:54:31Z","timestamp":1760151271005,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003006","name":"ETH Zurich","doi-asserted-by":"publisher","award":["ETH-33 13-1"],"award-info":[{"award-number":["ETH-33 13-1"]}],"id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["CR32I2_146331","33CS30-134277","130865"],"award-info":[{"award-number":["CR32I2_146331","33CS30-134277","130865"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yvonne Jacob Foundation","award":["xx"],"award-info":[{"award-number":["xx"]}]},{"name":"Gilead Sciences (Switzerland)","award":["xx"],"award-info":[{"award-number":["xx"]}]},{"DOI":"10.13039\/501100006447","name":"University of Zurich","doi-asserted-by":"publisher","award":["CRPP"],"award-info":[{"award-number":["CRPP"]}],"id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Little is known about whether and how variation in the HIV-1 genome affects its transmissibility. Assessing which genomic features of HIV-1 are under positive or negative selection during transmission is challenging, because very few virus particles are typically transmitted, and random genetic drift can dilute genetic signals in the recipient virus population. We analyzed 30 transmitter\u2013recipient pairs from the Zurich Primary HIV Infection Study and the Swiss HIV Cohort Study using near full-length HIV-1 genomes. We developed a new statistical test to detect selection during transmission, called Selection Test in Transmission (SeTesT), based on comparing the transmitter and recipient virus population and accounting for the transmission bottleneck. We performed extensive simulations and found that sensitivity of detecting selection during transmission is limited by the strong population bottleneck of few transmitted virions. When pooling individual test results across patients, we found two candidate HIV-1 genomic features for affecting transmission, namely amino acid positions 3 and 18 of Vpu, which were significant before but not after correction for multiple testing. In summary, SeTesT provides a general framework for detecting selection based on genomic sequencing data of transmitted viruses. Our study shows that a higher number of transmitter\u2013recipient pairs is required to improve sensitivity of detecting selection.<\/jats:p>","DOI":"10.3390\/v14020406","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T20:28:59Z","timestamp":1645043339000},"page":"406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Detecting Selection in the HIV-1 Genome during Sexual Transmission Events"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4739-5110","authenticated-orcid":false,"given":"David","family":"Seifert","sequence":"first","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland"},{"name":"SIB Swiss Institute of Bioinformatics, 4058 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3082-8875","authenticated-orcid":false,"given":"Beda","family":"Joos","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4036-1030","authenticated-orcid":false,"given":"Dominique L.","family":"Braun","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"},{"name":"Institute of Medical Virology, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinna S.","family":"Oberle","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"},{"name":"Institute of Medical Virology, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne D.","family":"Schenkel","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"},{"name":"Institute of Medical Virology, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6873-0091","authenticated-orcid":false,"given":"Herbert","family":"Kuster","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"},{"name":"Institute of Medical Virology, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Grube","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrg","family":"B\u00f6ni","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Yerly","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, University Hospital Geneva, 1205 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0352-9797","authenticated-orcid":false,"given":"Vincent","family":"Aubert","sequence":"additional","affiliation":[{"name":"University Hospital Lausanne, Service of Immunology and Allergy, University Hospital Center, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4945-6511","authenticated-orcid":false,"given":"Thomas","family":"Klimkait","sequence":"additional","affiliation":[{"name":"Molecular Virology, Department of Biomedicine-Petersplatz, University of Basel, 4009 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-6723","authenticated-orcid":false,"given":"Huldrych F.","family":"G\u00fcnthard","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"},{"name":"Institute of Medical Virology, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-6119","authenticated-orcid":false,"given":"Niko","family":"Beerenwinkel","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland"},{"name":"SIB Swiss Institute of Bioinformatics, 4058 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4862-1503","authenticated-orcid":false,"given":"Karin J.","family":"Metzner","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"},{"name":"Institute of Medical Virology, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the Swiss HIV Cohort Study","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS (2021, December 09). Global HIV & AIDS Statistics\u20142020 Fact Sheets. Available online: https:\/\/www.unaids.org\/en\/resources\/fact-sheet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrmicro729","article-title":"Inhibiting sexual transmission of HIV-1 infection","volume":"1","author":"Shattock","year":"2003","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nrmicro3471","article-title":"Bottlenecks in HIV-1 transmission: Insights from the study of founder viruses","volume":"13","author":"Joseph","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"a006965","DOI":"10.1101\/cshperspect.a006965","article-title":"HIV Transmission","volume":"2","author":"Shaw","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S289","DOI":"10.1086\/655656","article-title":"HIV-1 transmission biology: Selection and characteristics of infecting viruses","volume":"202","author":"Sagar","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S1368-7646(02)00123-1","article-title":"Fitness of drug resistant HIV-1: Methodology and clinical implications","volume":"5","author":"Arts","year":"2002","journal-title":"Drug Resist. Updat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1874357900903010001","article-title":"The evolution of viruses in multi-host fitness landscapes","volume":"3","author":"Elena","year":"2009","journal-title":"Open Virol. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1534\/genetics.114.172312","article-title":"A framework for inferring fitness landscapes of patient-derived viruses using quasispecies theory","volume":"199","author":"Seifert","year":"2015","journal-title":"Genetics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1098\/rspb.2002.2097","article-title":"Procedures for reliable estimation of viral fitness from time-series data","volume":"269","author":"Bonhoeffer","year":"2002","journal-title":"Proc. Biol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nature12091","article-title":"HIV: Roadmaps to a vaccine","volume":"496","author":"Mouquet","year":"2013","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1128\/jvi.69.2.1001-1012.1995","article-title":"Genetic analysis of human immunodeficiency virus type 1 envelope V3 region isolates from mothers and infants after perinatal transmission","volume":"69","author":"Ahmad","year":"1995","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1126\/science.8356453","article-title":"Genotypic and phenotypic characterization of HIV-1 patients with primary infection","volume":"261","author":"Zhu","year":"1993","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6528","DOI":"10.1128\/JVI.79.10.6528-6531.2005","article-title":"Selection for human immunodeficiency virus type 1 envelope glycosylation variants with shorter V1\u2013V2 loop sequences occurs during transmission of certain genetic subtypes and may impact viral RNA levels","volume":"79","author":"Chohan","year":"2005","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.virol.2008.01.029","article-title":"Env length and N-linked glycosylation following transmission of human immunodeficiency virus Type 1 subtype B viruses","volume":"374","author":"Liu","year":"2008","journal-title":"Virology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1093\/infdis\/jix184","article-title":"Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1","volume":"215","author":"Choi","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1254031","DOI":"10.1126\/science.1254031","article-title":"HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck","volume":"345","author":"Carlson","year":"2014","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7552","DOI":"10.1073\/pnas.0802203105","article-title":"Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection","volume":"105","author":"Keele","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1126\/science.1093137","article-title":"Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission","volume":"303","author":"Derdeyn","year":"2004","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Haaland, R.E., Hawkins, P.A., Salazar-Gonzalez, J., Johnson, A., Tichacek, A., Karita, E., Manigart, O., Mulenga, J., Keele, B.F., and Shaw, G.M. (2009). Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000274"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1093\/cid\/cir725","article-title":"Characterization of Human Immunodeficiency Virus Type 1 (HIV-1) Diversity and Tropism in 145 Patients With Primary HIV-1 Infection","volume":"53","author":"Rieder","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1097\/01.aids.0000172879.20628.e1","article-title":"Review of sampling hard-to-reach and hidden populations for HIV surveillance","volume":"19","author":"Magnani","year":"2005","journal-title":"AIDS"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.virusres.2016.09.016","article-title":"Recent advances in inferring viral diversity from high-throughput sequencing data","volume":"239","author":"Seifert","year":"2017","journal-title":"Virus. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1093\/bioinformatics\/btab015","article-title":"V-pipe: A computational pipeline for assessing viral genetic diversity from high-throughput data","volume":"37","author":"Seifert","year":"2021","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5095","DOI":"10.1073\/pnas.96.9.5095","article-title":"Transmission bottlenecks as determinants of virulence in rapidly evolving pathogens","volume":"96","author":"Bergstrom","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00171-17","DOI":"10.1128\/JVI.00171-17","article-title":"Transmission Bottleneck Size Estimation from Pathogen Deep-Sequencing Data, with an Application to Human Influenza A Virus","volume":"91","author":"Weissman","year":"2017","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lumby, C.K., Nene, N.R., and Illingworth, C.J.R. (2018). A novel framework for inferring parameters of transmission from viral sequence data. PLoS Genet., 14.","DOI":"10.1101\/302331"},{"key":"ref_27","first-page":"e62105","article-title":"Asynchrony between virus diversity and antibody selection limits influenza virus evolution","volume":"9","author":"Morris","year":"2020","journal-title":"bioRxiv"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1093\/ije\/dyp321","article-title":"Cohort profile: The Swiss HIV Cohort study","volume":"39","author":"Ledergerber","year":"2010","journal-title":"Int. J. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1093\/infdis\/jiv012","article-title":"Assessing the Paradox Between Transmitted and Acquired HIV Type 1 Drug Resistance Mutations in the Swiss HIV Cohort Study From 1998 to 2012","volume":"212","author":"Yang","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1097\/QAD.0b013e328338e4de","article-title":"HIV-1 transmission after cessation of early antiretroviral therapy among men having sex with men","volume":"24","author":"Rieder","year":"2010","journal-title":"AIDS"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Oberle, C.S., Joos, B., Rusert, P., Campbell, N.K., Beauparlant, D., Kuster, H., Weber, J., Schenkel, C.D., Scherrer, A.U., and Magnus, C. (2016). Tracing HIV-1 transmission: Envelope traits of HIV-1 transmitter and recipient pairs. Retrovirology, 13.","DOI":"10.1186\/s12977-016-0299-0"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1093\/nar\/gku537","article-title":"Full-length haplotype reconstruction to infer the structure of heterogeneous virus populations","volume":"42","author":"Giallonardo","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/bioinformatics\/btr026","article-title":"Quality control and preprocessing of metagenomic datasets","volume":"27","author":"Schmieder","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: Improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.1093\/nar\/gku1341","article-title":"Insight into biases and sequencing errors for amplicon sequencing with the Illumina MiSeq platform","volume":"43","author":"Schirmer","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_36","first-page":"1","article-title":"Contributions to the theory of testing statistical hypotheses","volume":"1","author":"Neyman","year":"1936","journal-title":"Stat. Res. Mem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/gepi.21689","article-title":"Robust and Powerful Tests for Rare Variants Using Fisher\u2019s Method to Combine Evidence of Association From Two or More Complementary Tests","volume":"37","author":"Derkach","year":"2013","journal-title":"Genet. Epidemiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.virol.2009.12.030","article-title":"Long sequence duplications, repeats, and palindromes in HIV-1 gp120: Length variation in V4 as the product of misalignment mechanism","volume":"399","author":"Guglietta","year":"2010","journal-title":"Virology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1089\/aid.2011.0206","article-title":"Diversity of HIV type 1 envelope (V3-V5) sequence in HIV type 1-infected Indian children","volume":"28","author":"Prakash","year":"2012","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5062","DOI":"10.1128\/JVI.03472-13","article-title":"Activities of Transmitted\/Founder and Chronic Clade B HIV-1 Vpu and a C-Terminal Polymorphism Specifically Affecting Virion Release","volume":"88","author":"Jafari","year":"2014","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4352","DOI":"10.3390\/v7082824","article-title":"Vpu Protein: The Viroporin Encoded by HIV-1","volume":"7","author":"Gonzalez","year":"2015","journal-title":"Viruses"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1128\/JVI.05933-11","article-title":"Transmembrane domain determinants of CD4 Downregulation by HIV-1 Vpu","volume":"86","author":"Magadan","year":"2012","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8540","DOI":"10.1128\/JVI.00522-15","article-title":"Primer ID Validates Template Sampling Depth and Greatly Reduces the Error Rate of Next Generation Sequencing of HIV-1 Genomic RNA Populations","volume":"89","author":"Zhou","year":"2015","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jmb.2015.12.012","article-title":"A Comprehensive Analysis of Primer IDs to Study Heterogeneous HIV-1 Populations","volume":"428","author":"Seifert","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/emmm.201202232","article-title":"R5 HIV-1 envelope attracts dendritic cells to cross the human intestinal epithelium and sample luminal virions via engagement of the CCR5","volume":"5","author":"Cavarelli","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1097\/QAD.0000000000000298","article-title":"Estimating per-act HIV transmission risk: A systematic review","volume":"28","author":"Patel","year":"2014","journal-title":"AIDS"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S1473-3099(09)70021-0","article-title":"Heterosexual risk of HIV-1 infection per sexual act: Systematic review and meta-analysis of observational studies","volume":"9","author":"Boily","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Agresti, A., and Gottard, A. (2006). Reducing conservatism of exact small-sample methods of inference for discrete data. Compstat 2006, Proceedings in Computational Statistics, Rome, Italy, 23 March 2006, Springer.","DOI":"10.1007\/978-3-7908-1709-6_19"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"E1156","DOI":"10.1073\/pnas.1103764108","article-title":"Role of donor genital tract HIV-1 diversity in the transmission bottleneck","volume":"108","author":"Boeras","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nm0297-205","article-title":"Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus","volume":"3","author":"Borrow","year":"1997","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1073\/pnas.94.5.1890","article-title":"Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection","volume":"94","author":"Price","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/2\/406\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:21:11Z","timestamp":1760134871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/2\/406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,16]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["v14020406"],"URL":"https:\/\/doi.org\/10.3390\/v14020406","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2022,2,16]]}}}