Identifying Recombination Hot Spots in the HIV-1 Genome
Smyth, R.P., Schlub, T.E., Grimm, A.J., Waugh, C., Ellenberg, P., Chopra, A., Mallal, S., Cromer, D., Mak, J., Davenport, M.P. and Hahn, B.H. (2014) Identifying Recombination Hot Spots in the HIV-1 Genome. Journal of Virology, 88 (5). pp. 2891-2902.
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HIV-1 infection is characterised by the rapid generation of genetic diversity that facilitates viral escape from immune selection and antiretroviral therapy. Despite recombination's crucial role in viral diversity and evolution, little is known about the genomic factors that influence recombination between highly similar genomes. In this study, we use a minimally modified full length HIV-1 genome and high throughput sequence analysis to study recombination in gag and pol in T cells. We find that recombination is favoured at a number of recombination hotspots, where recombination occurs six times more frequently than at corresponding coldspots. Interestingly, these hotspots occur near important features of the HIV-1 genome, but do not occur at sites immediately around protease inhibitor or reverse transcriptase inhibitor drug resistance mutations. We show that the recombination hot and cold spots are consistent across five blood donors and are independent of co-receptor mediated entry. Finally, we check common experimental confounders and find that these are not driving the location of recombination hotspots. This is the first study to identify the location of recombination hotspots, between two similar viral genomes with great statistical power and under conditions that closely reflect natural recombination events amongst HIV-1 quasispecies.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||Institute for Immunology and Infectious Diseases|
|Publisher:||American Society for Microbiology|
|Copyright:||© 2013, American Society for Microbiology|
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