Recombination leads to the rapid emergence of HIV-1 dually resistant mutants under selective drug pressure.
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.
Moutouh
L
L
Department of Pathology, University of California, San Diego, 92093-0679, USA.
Corbeil
J
J
Richman
D D
DD
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004352:Drug Resistance, Microbial / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects; D011995:Recombination, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D012692:Serial Passage; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D014508:Urea; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016333:HIV Protease; C079293:SC 52151