HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC

Simple item page
dc.contributor.authorWood, Natashaen_ZA
dc.contributor.authorBhattacharya, Tanmoyen_ZA
dc.contributor.authorKeele, Brandon Fen_ZA
dc.contributor.authorGiorgi, Elenaen_ZA
dc.contributor.authorLiu, Michaelen_ZA
dc.contributor.authorGaschen, Brianen_ZA
dc.contributor.authorDaniels, Marcusen_ZA
dc.contributor.authorFerrari, Guidoen_ZA
dc.contributor.authorHaynes, Barton Fen_ZA
dc.contributor.authorMcMichael, Andrewen_ZA
dc.date.accessioned2016-01-02T05:05:53Z
dc.date.available2016-01-02T05:05:53Z
dc.date.issued2009en_ZA
dc.description.abstractAuthor Summary HIV is a rapidly evolving virus, displaying enormous genetic diversity between and even within infected individuals, with implications for vaccine design and drug treatment. Yet, recent research has shown that most new infections result from transmission of a single virus resulting in a homogeneous viral population in early infection. The process of diversification from the transmitted virus provides information about the selection pressures experienced by the virus during the establishment of a new infection. In this paper, we studied early diversification of the envelope gene in a cohort of 81 subjects acutely infected with HIV-1 subtype B and found evidence of adaptive evolution, with a proportion of sites that tended to diversify more rapidly than expected under a model of neutral evolution. Several of these rapidly diversifying sites facilitate escape from early cytotoxic immune responses. Interestingly, hypermutation of the virus, brought about by host proteins as a strategy to restrict infection, appeared to be associated with early immune escape. In addition to single base substitutions, insertions and deletions are an important aspect of HIV evolution. We show that insertion and deletion mutations occur evenly across the gene, but are preferentially fixed in the variable loop regions.en_ZA
dc.identifier.apacitationWood, N., Bhattacharya, T., Keele, B. F., Giorgi, E., Liu, M., Gaschen, B., ... McMichael, A. (2009). HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC. <i>PLoS One</i>, http://hdl.handle.net/11427/16168en_ZA
dc.identifier.chicagocitationWood, Natasha, Tanmoy Bhattacharya, Brandon F Keele, Elena Giorgi, Michael Liu, Brian Gaschen, Marcus Daniels, Guido Ferrari, Barton F Haynes, and Andrew McMichael "HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC." <i>PLoS One</i> (2009) http://hdl.handle.net/11427/16168en_ZA
dc.identifier.citationWood, N., Bhattacharya, T., Keele, B. F., Giorgi, E., Liu, M., Gaschen, B., ... & Shaw, G. M. (2009). HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC. PLoS Pathog, 5(5), e1000414. doi:10.1371/journal.ppat.1000414en_ZA
dc.identifier.ris TY - Journal Article AU - Wood, Natasha AU - Bhattacharya, Tanmoy AU - Keele, Brandon F AU - Giorgi, Elena AU - Liu, Michael AU - Gaschen, Brian AU - Daniels, Marcus AU - Ferrari, Guido AU - Haynes, Barton F AU - McMichael, Andrew AB - Author Summary HIV is a rapidly evolving virus, displaying enormous genetic diversity between and even within infected individuals, with implications for vaccine design and drug treatment. Yet, recent research has shown that most new infections result from transmission of a single virus resulting in a homogeneous viral population in early infection. The process of diversification from the transmitted virus provides information about the selection pressures experienced by the virus during the establishment of a new infection. In this paper, we studied early diversification of the envelope gene in a cohort of 81 subjects acutely infected with HIV-1 subtype B and found evidence of adaptive evolution, with a proportion of sites that tended to diversify more rapidly than expected under a model of neutral evolution. Several of these rapidly diversifying sites facilitate escape from early cytotoxic immune responses. Interestingly, hypermutation of the virus, brought about by host proteins as a strategy to restrict infection, appeared to be associated with early immune escape. In addition to single base substitutions, insertions and deletions are an important aspect of HIV evolution. We show that insertion and deletion mutations occur evenly across the gene, but are preferentially fixed in the variable loop regions. DA - 2009 DB - OpenUCT DO - 10.1371/journal.ppat.1000414 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC TI - HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC UR - http://hdl.handle.net/11427/16168 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16168
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.1000414
dc.identifier.vancouvercitationWood N, Bhattacharya T, Keele BF, Giorgi E, Liu M, Gaschen B, et al. HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC. PLoS One. 2009; http://hdl.handle.net/11427/16168.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_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 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2009 Wood et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherSequence motif analysisen_ZA
dc.subject.otherSequence alignmenten_ZA
dc.subject.otherNatural selectionen_ZA
dc.subject.otherSubstitution mutationen_ZA
dc.subject.otherHIV-1en_ZA
dc.subject.otherViral evolutionen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherEvolutionary immunologyen_ZA
dc.titleHIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBECen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Wood_HIV_Evolution_2009.pdf
Size:
653.06 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles