AEGiS-14IAC: The majority of HIV-1 positive cells in vivo are multiply infected with divergent viruses culminating in rampant recombination.

14th International AIDS Conference


Barcelona, Spain - July 7-12, 2002

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The majority of HIV-1 positive cells in vivo are multiply infected with divergent viruses culminating in rampant recombination.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1380)

Meyerhans A, Jung A, Maier R, Jung V, Fischer U, Meese E, Bocharov G, Vartanian JP, Wain-Hobson S
University of the Saarland, Homburg, Germany

BACKGROUND: From a posterori 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, something that has not been readily forthcoming in vivo.

METHODS: Fluorescent in situ hybridisation has been used to identify proviruses in splenocytes from two HIV-1 patients. Individual cells were laser microdissected and the HIV genomes were amplified by PCR. Amplified DNA of the hypervariable V1V2 regions of Env was cloned and several clones were sequenced.

RESULTS: More than 75% of infected splenocytes harboured two or more proviruses, range 1-8, with a mean of ~3-4 per cell. Extrapolation of the frequency distribution of cellular proviral copy number indicated an upper limit of ~14-16 copies/cell. The distributions were remarkably similar for the two patients despite different clinical and virological settings. Sequencing of amplified HIV DNA from individual cells showed an extraordinary degree of diversity - up to 29% amino acid difference. Furthermore numerous recombinants were evident.

CONCLUSIONS: Given the dynamics of HIV-1 turnover in vivo and a recombination rate of ~3 cross-overs per cycle, genomes from a fifteen year old infection may have undergone as many cross-overs as bases in the genome. Recombination profoundly influences HIV evolution and presents a huge challenge to its analysis.

Keywords: AEGIS, HIV-1, Proviruses, Recombination, Genetic, HIV Infections, AIDS Dementia Complex, HIV Seropositivity, Variation (Genetics), Polymerase Chain Reaction, Human, virology, geneticsKWDaegis,hiv-1,proviruses,recombination,genetic,hivinfections,aidsdementiacomplex,hivseropositivity,variation(genetics),polymerasechainreaction,human,virology,genetics

020707
ThOrA1380

Copyright © 2002 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.