Recombination profoundly influences HIV evolution & 8/23/03 SMW

In the 8/23/03 Swiss Medical Weekly article titled "The non-clonal and
transitory nature of HIV in vivo," Meyerhans et al. (Wain-Hobson is
senior author) state:

"Even SIVcpz, the suspected founder of HIV-1 in humans, was recently
shown to be a recombinant of 2 SIVs from different species."

"Assuming that there are few recombination hot spots then a 9200
nucleotide genome should be marked by approximately as many
recombination sites as nucleotides in the genome. The effects of such
rampant recombination on phylogenic analyses of HIV need to be
addressed. For example, simulations of sequence evolution allowing
recombination have indicated that the molecular clock breaks down, while
branch lengths appear to be overestimated. However, the degree of
recombination postulated was low compared to that indicated by the
present study."

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Meyerhans A, Jung A, Maier R, Vartanian JP, Bocharov G, Wain-Hobson S.
The non-clonal and transitory nature of HIV in vivo. Swiss Med Wkly.
2003 Aug 23;133(33-34):451-4.

Department of Virology, University of the Saarland, Homburg, Germany.

Abstract: 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. Using fluorescence in situ hybridisation, the
provirus copy numbers in splenocytes from two HIV-1 patients were
determined. More than 75% of infected splenocytes harboured two or more
proviruses, range 1-8, with a mean of approximately 3-4 per cell.
Sequencing of amplified DNA from single laser micro-dissected cells
showed an extraordinary degree of diversity while numerous recombinants
were evident. Given the dynamics of HIV-1 turnover in vivo and a
recombination rate of approximately 3 cross-overs per cycle, some
genomes from a fifteen year old infection may have undergone as many
cross-overs as bases in the genome. Thus, recombination profoundly
influences HIV evolution and gives it a non-clonal and transitory nature
in vivo.