Open AccessRecombination leads to the rapid emergence of HIV-1 dually resistant mutants under selective drug pressure.
Author(s) -
Laure Moutouh,
Jacques Corbeil,
Douglas D. Richman
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.12.6106
Subject(s) - zidovudine , biology , virology , drug resistance , genotype , viral quasispecies , mutant , recombination , mutation , virus , genetics , genetic recombination , reverse transcriptase , viral evolution , gene , viral disease , rna , hepatitis c virus
The potential contribution of recombination to the development of HIV-1 resistance to multiple drugs was investigated. Two distinct viruses, one highly resistant to a protease inhibitor (SC-52151) and the other highly resistant to zidovudine, were used to coinfect T lymphoblastoid cells in culture. The viral genotypes could be distinguished by four mutations conferring drug resistance to each drug and by other sequence differences specific for each parental virus. Progeny virions recovered from mixed infection were passaged in the presence and absence of both zidovudine and SC-52151. Dually resistant mutants emerged rapidly under selective conditions, and these viruses were genetic recombinants. These results emphasize that genetic recombination could contribute to high-level multiple-drug resistance and that this process must be considered in chemotherapeutic strategies for HIV infection.