The role of recombination in HIV evolution

Poster number: 3

Andreas Meyerhans1, Tanja Breinig1, Jochen Reiter1, Jean-Pierre Vartanian2, Simon Wain-Hobson2, and Gennady Bocharov3

  1. Department of Virology, University of the Saarland, D-66421 Homburg
  2. Unité de Rétrovirologie Moléculaire, Institut Pasteur, F-75724 Paris cedex 15
  3. Institute of Numerical Mathematics, Russian Academy of Sciences, Moscow

From a posteriori analyses of genetic variation, recombination can only be identified when the parental genomes are distinct. For viruses like HIV-1, this requires the producer cell to be infected by more than one virus. By fluorescence in situ hybridization, the provirus copy numbers in splenocytes from two HIV-1 patients have been determined. The majority of the infected splenocytes harboured two or more proviruses per cell. Sequencing of amplified DNA from single laser microdissected cells showed an extraordinary degree of diversity while numerous recombinants were evident. These data together with the known recombination rate of ~3 to 30 cross-overs per cycle enabled us to develope an in silico stochastic model and explore the effects of major microscopic parameters (e.g. the point mutation and recombination rates, the proviral copy number per cell, etc.) on the dynamics of macroscopic characteristics such as the genetic distance and the abundance of n-point mutants. The model seeks to accommodate the rapid turnover and restriction of HIV replication observed in vivo. It is shown that both multi-infection and recombination serve to accelerate viral diversity even in situations where there is no selection. Studies on the role of recombination for the evolution of drug resistance are ongoing.