Constraints from protein structure and intra-molecular coevolution influence the fitness of HIV-1 recombinants

Woo, J., Robertson, D. L. and Lovell, S. C. (2014) Constraints from protein structure and intra-molecular coevolution influence the fitness of HIV-1 recombinants. Virology, 454-45, pp. 34-39. (doi: 10.1016/j.virol.2014.01.029) (PMID:24725929)

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Abstract

A major challenge for developing effective treatments for HIV-1 is the viruses' ability to generate new variants. Inter-strain recombination is a major contributor to this high evolutionary rate, since at least 20% of viruses are observed to be recombinant. However, the patterns of recombination vary across the viral genome. A number of factors influence recombination, including sequence identity and secondary RNA structure. In addition the recombinant genome must code for a functional virus, and expressed proteins must fold to stable and functional structures. Any intragenic recombination that disrupts internal residue contacts may therefore produce an unfolded protein. Here we find that contact maps based on protein structures predict recombination breakpoints observed in the HIV-1 pandemic. Moreover, many pairs of contacting residues that are unlikely to be disrupted by recombination are coevolving. We conclude that purifying selection arising from protein structure and intramolecular coevolutionary changes shapes the observed patterns of recombination in HIV-1.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robertson, Professor David
Authors: Woo, J., Robertson, D. L., and Lovell, S. C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Virology
Publisher:Elsevier
ISSN:0042-6822
ISSN (Online):1096-0341
Published Online:22 February 2014

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