Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.
Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for H...
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Public Library of Science (PLoS)
2012
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oai:doaj.org-article:30936a9dc7f44f478975974860e15f412021-11-18T06:04:22ZTransmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.1553-73661553-737410.1371/journal.ppat.1002686https://doaj.org/article/30936a9dc7f44f478975974860e15f412012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22693444/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently.Nicholas F ParrishCraig B WilenLauren B BanksShilpa S IyerJennifer M PfaffJesus F Salazar-GonzalezMaria G SalazarJulie M DeckerErica H ParrishAnna BergJennifer HopperBhavna HoraAmit KumarTatenda MahlokozeraSally YuanCharl ColemanMarion VermeulenHaitao DingChristina OchsenbauerJohn C TiltonSallie R PermarJohn C KappesMichael R BettsMichael P BuschFeng GaoDavid MontefioriBarton F HaynesGeorge M ShawBeatrice H HahnRobert W DomsPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 5, p e1002686 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Nicholas F Parrish Craig B Wilen Lauren B Banks Shilpa S Iyer Jennifer M Pfaff Jesus F Salazar-Gonzalez Maria G Salazar Julie M Decker Erica H Parrish Anna Berg Jennifer Hopper Bhavna Hora Amit Kumar Tatenda Mahlokozera Sally Yuan Charl Coleman Marion Vermeulen Haitao Ding Christina Ochsenbauer John C Tilton Sallie R Permar John C Kappes Michael R Betts Michael P Busch Feng Gao David Montefiori Barton F Haynes George M Shaw Beatrice H Hahn Robert W Doms Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. |
| description |
Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently. |
| format |
article |
| author |
Nicholas F Parrish Craig B Wilen Lauren B Banks Shilpa S Iyer Jennifer M Pfaff Jesus F Salazar-Gonzalez Maria G Salazar Julie M Decker Erica H Parrish Anna Berg Jennifer Hopper Bhavna Hora Amit Kumar Tatenda Mahlokozera Sally Yuan Charl Coleman Marion Vermeulen Haitao Ding Christina Ochsenbauer John C Tilton Sallie R Permar John C Kappes Michael R Betts Michael P Busch Feng Gao David Montefiori Barton F Haynes George M Shaw Beatrice H Hahn Robert W Doms |
| author_facet |
Nicholas F Parrish Craig B Wilen Lauren B Banks Shilpa S Iyer Jennifer M Pfaff Jesus F Salazar-Gonzalez Maria G Salazar Julie M Decker Erica H Parrish Anna Berg Jennifer Hopper Bhavna Hora Amit Kumar Tatenda Mahlokozera Sally Yuan Charl Coleman Marion Vermeulen Haitao Ding Christina Ochsenbauer John C Tilton Sallie R Permar John C Kappes Michael R Betts Michael P Busch Feng Gao David Montefiori Barton F Haynes George M Shaw Beatrice H Hahn Robert W Doms |
| author_sort |
Nicholas F Parrish |
| title |
Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. |
| title_short |
Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. |
| title_full |
Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. |
| title_fullStr |
Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. |
| title_full_unstemmed |
Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. |
| title_sort |
transmitted/founder and chronic subtype c hiv-1 use cd4 and ccr5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/30936a9dc7f44f478975974860e15f41 |
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