HIV-1 <i>Gag-Pol</i> Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity
The ability to efficiently establish a new infection is a critical property for human immunodeficiency virus type 1 (HIV-1). Although the envelope protein of the virus plays an essential role in receptor binding and internalization of the infecting virus, the structural proteins, the polymerase and...
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| Language: | English |
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MDPI AG
2021-01-01
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| Online Access: | https://www.mdpi.com/1999-4915/13/2/171 |
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| author | Anne Kapaata Sheila N. Balinda Rui Xu Maria G. Salazar Kimberly Herard Kelsie Brooks Kato Laban Jonathan Hare Dario Dilernia Anatoli Kamali Eugene Ruzagira Freddie Mukasa Jill Gilmour Jesus F. Salazar-Gonzalez Ling Yue Matthew Cotten Eric Hunter Pontiano Kaleebu |
| author_facet | Anne Kapaata Sheila N. Balinda Rui Xu Maria G. Salazar Kimberly Herard Kelsie Brooks Kato Laban Jonathan Hare Dario Dilernia Anatoli Kamali Eugene Ruzagira Freddie Mukasa Jill Gilmour Jesus F. Salazar-Gonzalez Ling Yue Matthew Cotten Eric Hunter Pontiano Kaleebu |
| author_sort | Anne Kapaata |
| collection | DOAJ |
| description | The ability to efficiently establish a new infection is a critical property for human immunodeficiency virus type 1 (HIV-1). Although the envelope protein of the virus plays an essential role in receptor binding and internalization of the infecting virus, the structural proteins, the polymerase and the assembly of new virions may also play a role in establishing and spreading viral infection in a new host. We examined Ugandan viruses from newly infected patients and focused on the contribution of the <i>Gag-Pol</i> genes to replication capacity. A panel of <i>Gag-Pol</i> sequences generated using single genome amplification from incident HIV-1 infections were cloned into a common HIV-1 NL4.3 pol/env backbone and the influence of <i>Gag-Pol</i> changes on replication capacity was monitored. Using a novel protein domain approach, we then documented diversity in the functional protein domains across the <i>Gag-Pol</i> region and identified differences in the Gag-p6 domain that were frequently associated with higher in vitro replication. |
| first_indexed | 2024-03-09T03:50:42Z |
| format | Article |
| id | doaj.art-a13e42cdcef44f76bc46e52c1ad6574a |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T03:50:42Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a13e42cdcef44f76bc46e52c1ad6574a2023-12-03T14:28:52ZengMDPI AGViruses1999-49152021-01-0113217110.3390/v13020171HIV-1 <i>Gag-Pol</i> Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication CapacityAnne Kapaata0Sheila N. Balinda1Rui Xu2Maria G. Salazar3Kimberly Herard4Kelsie Brooks5Kato Laban6Jonathan Hare7Dario Dilernia8Anatoli Kamali9Eugene Ruzagira10Freddie Mukasa11Jill Gilmour12Jesus F. Salazar-Gonzalez13Ling Yue14Matthew Cotten15Eric Hunter16Pontiano Kaleebu17Medical Research Council, UVRI & LSTHM Uganda Research Unit, Plot 51–59, Entebbe, UgandaMedical Research Council, UVRI & LSTHM Uganda Research Unit, Plot 51–59, Entebbe, UgandaEmory University, Atlanta, GA 30322, USAMedical Research Council, UVRI & LSTHM Uganda Research Unit, Plot 51–59, Entebbe, UgandaEmory University, Atlanta, GA 30322, USAEmory University, Atlanta, GA 30322, USAMedical Research Council, UVRI & LSTHM Uganda Research Unit, Plot 51–59, Entebbe, UgandaImperial College London, London SW7 2AZ, UKEmory University, Atlanta, GA 30322, USAIAVI, Nairobi 00202, KenyaMedical Research Council, UVRI & LSTHM Uganda Research Unit, Plot 51–59, Entebbe, UgandaMedical Research Council, UVRI & LSTHM Uganda Research Unit, Plot 51–59, Entebbe, UgandaImperial College London, London SW7 2AZ, UKMedical Research Council, UVRI & LSTHM Uganda Research Unit, Plot 51–59, Entebbe, UgandaEmory University, Atlanta, GA 30322, USAMedical Research Council, UVRI & LSTHM Uganda Research Unit, Plot 51–59, Entebbe, UgandaEmory University, Atlanta, GA 30322, USAMedical Research Council, UVRI & LSTHM Uganda Research Unit, Plot 51–59, Entebbe, UgandaThe ability to efficiently establish a new infection is a critical property for human immunodeficiency virus type 1 (HIV-1). Although the envelope protein of the virus plays an essential role in receptor binding and internalization of the infecting virus, the structural proteins, the polymerase and the assembly of new virions may also play a role in establishing and spreading viral infection in a new host. We examined Ugandan viruses from newly infected patients and focused on the contribution of the <i>Gag-Pol</i> genes to replication capacity. A panel of <i>Gag-Pol</i> sequences generated using single genome amplification from incident HIV-1 infections were cloned into a common HIV-1 NL4.3 pol/env backbone and the influence of <i>Gag-Pol</i> changes on replication capacity was monitored. Using a novel protein domain approach, we then documented diversity in the functional protein domains across the <i>Gag-Pol</i> region and identified differences in the Gag-p6 domain that were frequently associated with higher in vitro replication.https://www.mdpi.com/1999-4915/13/2/171HIV-1Ugandarecombinant<i>Gag-Pol</i>protein domains |
| spellingShingle | Anne Kapaata Sheila N. Balinda Rui Xu Maria G. Salazar Kimberly Herard Kelsie Brooks Kato Laban Jonathan Hare Dario Dilernia Anatoli Kamali Eugene Ruzagira Freddie Mukasa Jill Gilmour Jesus F. Salazar-Gonzalez Ling Yue Matthew Cotten Eric Hunter Pontiano Kaleebu HIV-1 <i>Gag-Pol</i> Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity Viruses HIV-1 Uganda recombinant <i>Gag-Pol</i> protein domains |
| title | HIV-1 <i>Gag-Pol</i> Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity |
| title_full | HIV-1 <i>Gag-Pol</i> Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity |
| title_fullStr | HIV-1 <i>Gag-Pol</i> Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity |
| title_full_unstemmed | HIV-1 <i>Gag-Pol</i> Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity |
| title_short | HIV-1 <i>Gag-Pol</i> Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity |
| title_sort | hiv 1 i gag pol i sequences from ugandan early infections reveal sequence variants associated with elevated replication capacity |
| topic | HIV-1 Uganda recombinant <i>Gag-Pol</i> protein domains |
| url | https://www.mdpi.com/1999-4915/13/2/171 |
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