Variability at Human Immunodeficiency Virus Type 1 Subtype C Protease Cleavage Sites : an indication of viral fitness

Show simple item record De Oliveira, Tulio Engelbrecht, Susan Janse van Rensburg, Estrelita Gordon, Michelle Bishop, Karen Zur Megede, Jan Barnett, Susan W.
dc.contributor.upauthor Cassol, Sharon 2007-06-23T10:19:22Z 2007-06-23T10:19:22Z 2003-09
dc.description This article was written by Prof Janse van Rensburg and Prof Cassol before they joined the University of Pretoria. en
dc.description.abstract Naturally occurring polymorphisms in the protease of human immunodeficiency virus type 1 (HIV-1)subtype C would be expected to lead to adaptive (compensatory) changes in protease cleavage sites. To test this hypothesis, we examined the prevalences and patterns of cleavage site polymorphisms in the Gag, Gag-Pol, and Nef cleavage sites of C compared to those in non-C subtypes. Codon-based maximum-likelihood methods were used to assess the natural selection and evolutionary history of individual cleavage sites. Seven cleavage sites (p17/p24, p24/p2, NC/p1, NC/TFP, PR/RT, RT/p66, and p66/IN) were well conserved over time and in all HIV-1 subtypes. One site (p1/p6gag) exhibited moderate variation, and four sites (p2/NC, TFP/p6pol, p6pol/PR, and Nef) were highly variable, both within and between subtypes. Three of the variable sites are known to be major determinants of polyprotein processing and virion production. P2/NC controls the rate and order of cleavage, p6gag is an important phosphoprotein required for virion release, and TFP/p6pol, a novel cleavage site in the transframe domain, influences the specificity of Gag-Pol processing and the activation of protease. Overall, 58.3% of the 12 HIV-1 cleavage sites were significantly more diverse in C than in B viruses. When analyzed as a single concatenated fragment of 360 bp, 96.0% of group M cleavage site sequences fell into subtype-specific phylogenetic clusters, suggesting that they coevolved with the virus. Natural variation at C cleavage sites may play an important role, not only in regulation of the viral cycle but also in disease progression and response to therapy. en
dc.description.sponsorship Wellcome Trust (United Kingdom) (grant number 061238/2/00/2 to S.C.), NIH HIV Vaccine Design and Development Team (contract number NO1-AI-05396 to S.W.B.) and the Poliomyelitis Research Foundation (PRF) and the Harry Crossley Foundation (to S.E.). en
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dc.identifier.citation De Oliveira, T, Engelbrecht, S, Janse van Rensburg, E, Gordon, M, Bishop, K, Zur Megede, J, Barnett, SW & Cassol, S 2003, 'Variability at Human Immunodeficiency Virus Type 1 Subtype C Protease Cleavage Sites: an indication of viral fitness', Journal of Virology, vol.77, no. 17, pp. 9422-9430. [] en
dc.identifier.issn 0022-538X
dc.identifier.other 10.1128/JVI.77.17.9422–9430.2003
dc.language.iso en en
dc.publisher American Society for Microbiology en
dc.rights American Society for Microbiology en
dc.subject HIV-1 en
dc.subject.lcsh HIV (Viruses)
dc.subject.lcsh Virus diseases -- Research
dc.subject.lcsh Natural immunity
dc.title Variability at Human Immunodeficiency Virus Type 1 Subtype C Protease Cleavage Sites : an indication of viral fitness en
dc.type Article en

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