1st National Conference Human Retroviruses and Related Infections Washington, DC - December 12-16, 1993

Natl Conf Hum Retrovir Relat Infect 1993 Dec 12-16;1: (abstract no. 6)

Gao Q, Fang H, Gu Z, Wainberg MA
McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada

To assess the possibility that the syncytium-inducing (SI) phenotype of HIV-1 might be related to genetic recombination and the development of multiple drug resistance, U-937 cells that had been infected with viruses resistant to either 3′-deoxy-3′deoxythymidine (AZT) or 2′,3′-deoxythiacytidine (3TC) were fused with polyethylene glycol (PEG). (Similar attempts with lymphocytes were unsuccessful due to PEG-related toxicity and non-viability of hybrids.) Eight large polymorphonuclear cells (hybrid cells) were selected under microscopy using a large bore pipette for co- culture with previously uninfected MT-4 cells. Eight of 9 such co-cultures produced infectious progeny within 4-6 days, as demonstrated by appearance of syncytia, detectable RT activity, and presence of p24 Ag in culture fluids. The viruses generated in 5 of 8 cases possessed resistance to either AZT or 3TC, indicating that the hybrids in question may have involved fusions among cells of similar phenotype or that no recombination had occurred. The viral progeny of these hybrids contained, as expected, mutations at either site 184, in the case of 3TC, or sites 70 and 215, for AZT. In 3 instances, viral progeny were 40-50 fold resistant against AZT and 90-120 fold against 3TC, in comparison with wild-type HXB2-D. Sequencing and PCR analysis showed that these dually resistant variants contained the expected mutations at each of sites 70, 184 and 215 or, alternatively at sites 184 and 215 only.

Keywords: Drug Resistance, HIV-1, HIV-1 Reverse Transcriptase, Humans, Lamivudine, Mutation, Pharmaceutical Preparations, Single Person, Zidovudine, genetics

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1993-12-12
6

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