Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection

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dc.contributor.authorBandawe, Gamaen_ZA
dc.contributor.authorMartin, Darrenen_ZA
dc.contributor.authorTreurnicht, Floretteen_ZA
dc.contributor.authorMlisana, Kolekaen_ZA
dc.contributor.authorKarim, Salimen_ZA
dc.contributor.authorWilliamson, Carolynen_ZA
dc.date.accessioned2015-10-12T10:57:15Z
dc.date.available2015-10-12T10:57:15Z
dc.date.issued2008en_ZA
dc.description.abstractBACKGROUND:The high diversity of HIV variants driving the global AIDS epidemic has caused many to doubt whether an effective vaccine against the virus is possible. However, by identifying the selective forces that are driving the ongoing diversification of HIV and characterising their genetic consequences, it may be possible to design vaccines that pre-empt some of the virus' more common evasion tactics. One component of such vaccines might be the envelope protein, gp41. Besides being targeted by both the humoral and cellular arms of the immune system this protein mediates fusion between viral and target cell membranes and is likely to be a primary determinant of HIV transmissibility. RESULTS: Using recombination aware analysis tools we compared site specific signals of selection in gp41 sequences from different HIV-1 M subtypes and circulating recombinant forms and identified twelve sites evolving under positive selection across multiple major HIV-1 lineages. To identify evidence of selection operating during transmission our analysis included two matched datasets sampled from patients with acute or chronic subtype C infections. We identified six gp41 sites apparently evolving under different selection pressures during acute and chronic HIV-1 infections. These sites mostly fell within functional gp41 domains, with one site located within the epitope recognised by the broadly neutralizing antibody, 4E10. CONCLUSION: Whereas these six sites are potentially determinants of fitness and are therefore good candidate targets for subtype-C specific vaccines, the twelve sites evolving under diversifying selection across multiple subtypes might make good candidate targets for broadly protective vaccines.en_ZA
dc.identifier.apacitationBandawe, G., Martin, D., Treurnicht, F., Mlisana, K., Karim, S., & Williamson, C. (2008). Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection. <i>Virology Journal</i>, http://hdl.handle.net/11427/14188en_ZA
dc.identifier.chicagocitationBandawe, Gama, Darren Martin, Florette Treurnicht, Koleka Mlisana, Salim Karim, and Carolyn Williamson "Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection." <i>Virology Journal</i> (2008) http://hdl.handle.net/11427/14188en_ZA
dc.identifier.citationBandawe, G. P., Martin, D. P., Treurnicht, F., Mlisana, K., Karim, S. S. A., & Williamson, C. (2008). Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection. Virology journal, 5(1), 141.en_ZA
dc.identifier.ris TY - Journal Article AU - Bandawe, Gama AU - Martin, Darren AU - Treurnicht, Florette AU - Mlisana, Koleka AU - Karim, Salim AU - Williamson, Carolyn AB - BACKGROUND:The high diversity of HIV variants driving the global AIDS epidemic has caused many to doubt whether an effective vaccine against the virus is possible. However, by identifying the selective forces that are driving the ongoing diversification of HIV and characterising their genetic consequences, it may be possible to design vaccines that pre-empt some of the virus' more common evasion tactics. One component of such vaccines might be the envelope protein, gp41. Besides being targeted by both the humoral and cellular arms of the immune system this protein mediates fusion between viral and target cell membranes and is likely to be a primary determinant of HIV transmissibility. RESULTS: Using recombination aware analysis tools we compared site specific signals of selection in gp41 sequences from different HIV-1 M subtypes and circulating recombinant forms and identified twelve sites evolving under positive selection across multiple major HIV-1 lineages. To identify evidence of selection operating during transmission our analysis included two matched datasets sampled from patients with acute or chronic subtype C infections. We identified six gp41 sites apparently evolving under different selection pressures during acute and chronic HIV-1 infections. These sites mostly fell within functional gp41 domains, with one site located within the epitope recognised by the broadly neutralizing antibody, 4E10. CONCLUSION: Whereas these six sites are potentially determinants of fitness and are therefore good candidate targets for subtype-C specific vaccines, the twelve sites evolving under diversifying selection across multiple subtypes might make good candidate targets for broadly protective vaccines. DA - 2008 DB - OpenUCT DP - University of Cape Town J1 - Virology Journal LK - https://open.uct.ac.za PB - University of Cape Town PY - 2008 T1 - Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection TI - Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection UR - http://hdl.handle.net/11427/14188 ER - en_ZA
dc.identifier.uri10.1186/1743-422X-5-141en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14188
dc.identifier.vancouvercitationBandawe G, Martin D, Treurnicht F, Mlisana K, Karim S, Williamson C. Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection. Virology Journal. 2008; http://hdl.handle.net/11427/14188.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceVirology Journalen_ZA
dc.source.urihttp://www.virologyj.com/en_ZA
dc.subject.otherVaccination strategiesen_ZA
dc.subject.otherHIVen_ZA
dc.titleConserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infectionen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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