Oral Presentation Lorne Infection and Immunity 2013

Identifying recombination hotspots in the HIV genome (#26)

Johnson Mak 1 , Red P Smyth 2 , Timothy E Schlub 3 , Andrew J Grimm 4 , Abha Chopra 5 , Simon Mallal 5 , Deborah Cromer 6 , Miles Davenport 4
  1. Deakin University, CSIRO AAHL, East Geelong, VIC, Australia
  2. Université de Strasbourg, Strasbourg, France
  3. University of Sydney, Sydney, Australia
  4. University of New South Wales, Sydney, Australia
  5. Murdoch University, Perth, Australia
  6. University of New South Wales, Sydney, Australia

HIV infection is characterised by the rapid generation of genetic diversity that facilitates viral escape from immune selection and antiretroviral therapy. Genetic diversity results from high levels of mutation and recombination coupled with high viral turnover and strong selection. In HIV, recombination occurs much more frequently than mutation, leading to the rapid reassortment of mutations within the viral quasispecies. Despite recombination’s crucial role in viral 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 genome and high throughput sequence analysis to study recombination in gag and pol.  We find that recombination occurs on average 19-20 times per genome per replication cycle. We also find that recombination does not occur randomly, but 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 genome, but do not occur at known sites of drug resistance. We also show that the recombination hot and cold spots in T cells are consistent across five blood donors and are independent of co-receptor mediated entry. Finally, we check common experimental confounders and find that these effects 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 mimicking HIV quasispecies with great statistical power and under experimental conditions that closely reflect a natural infection.