Detecting Selection in the HIV-1 Genome during Sexual Transmission Events
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 drif...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/2/406 |
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| author | David Seifert Beda Joos Dominique L. Braun Corinna S. Oberle Corinne D. Schenkel Herbert Kuster Christina Grube Jürg Böni Sabine Yerly Vincent Aubert Thomas Klimkait Huldrych F. Günthard Niko Beerenwinkel Karin J. Metzner on behalf of the Swiss HIV Cohort Study |
| author_facet | David Seifert Beda Joos Dominique L. Braun Corinna S. Oberle Corinne D. Schenkel Herbert Kuster Christina Grube Jürg Böni Sabine Yerly Vincent Aubert Thomas Klimkait Huldrych F. Günthard Niko Beerenwinkel Karin J. Metzner on behalf of the Swiss HIV Cohort Study |
| author_sort | David Seifert |
| collection | DOAJ |
| description | 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–recipient 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–recipient pairs is required to improve sensitivity of detecting selection. |
| first_indexed | 2024-03-09T20:51:48Z |
| format | Article |
| id | doaj.art-a2d2a2e73e1c475f92e18d04fcf25821 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T20:51:48Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a2d2a2e73e1c475f92e18d04fcf258212023-11-23T22:32:23ZengMDPI AGViruses1999-49152022-02-0114240610.3390/v14020406Detecting Selection in the HIV-1 Genome during Sexual Transmission EventsDavid Seifert0Beda Joos1Dominique L. Braun2Corinna S. Oberle3Corinne D. Schenkel4Herbert Kuster5Christina Grube6Jürg Böni7Sabine Yerly8Vincent Aubert9Thomas Klimkait10Huldrych F. Günthard11Niko Beerenwinkel12Karin J. Metzner13on behalf of the Swiss HIV Cohort StudyDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandInstitute of Medical Virology, University of Zurich, 8091 Zurich, SwitzerlandLaboratory of Virology, University Hospital Geneva, 1205 Geneva, SwitzerlandUniversity Hospital Lausanne, Service of Immunology and Allergy, University Hospital Center, 1011 Lausanne, SwitzerlandMolecular Virology, Department of Biomedicine-Petersplatz, University of Basel, 4009 Basel, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandLittle 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–recipient 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–recipient pairs is required to improve sensitivity of detecting selection.https://www.mdpi.com/1999-4915/14/2/406HIV-1transmissiontransmitter–recipient pairsSelection Test in Transmission (SeTesT)VpuZPHI |
| spellingShingle | David Seifert Beda Joos Dominique L. Braun Corinna S. Oberle Corinne D. Schenkel Herbert Kuster Christina Grube Jürg Böni Sabine Yerly Vincent Aubert Thomas Klimkait Huldrych F. Günthard Niko Beerenwinkel Karin J. Metzner on behalf of the Swiss HIV Cohort Study Detecting Selection in the HIV-1 Genome during Sexual Transmission Events Viruses HIV-1 transmission transmitter–recipient pairs Selection Test in Transmission (SeTesT) Vpu ZPHI |
| title | Detecting Selection in the HIV-1 Genome during Sexual Transmission Events |
| title_full | Detecting Selection in the HIV-1 Genome during Sexual Transmission Events |
| title_fullStr | Detecting Selection in the HIV-1 Genome during Sexual Transmission Events |
| title_full_unstemmed | Detecting Selection in the HIV-1 Genome during Sexual Transmission Events |
| title_short | Detecting Selection in the HIV-1 Genome during Sexual Transmission Events |
| title_sort | detecting selection in the hiv 1 genome during sexual transmission events |
| topic | HIV-1 transmission transmitter–recipient pairs Selection Test in Transmission (SeTesT) Vpu ZPHI |
| url | https://www.mdpi.com/1999-4915/14/2/406 |
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