Inhibition by AZT of HIV-1 replication in acutely infected U-937 cells.
We studied the effect of AZT on the replication of HIV-1 in freshly and chronically infected U-937 monocytoid cells over a period of 2 months. Expression of viral antigens was monitored by indirect immunofluorescence, and viral replication was assessed by reverse transcriptase assay on virus pelleted from culture fluids. In U-937 cells not treated by AZT, viral antigens were expressed by 7 days after infection. The inclusion of a variety of concentrations of AZT in the culture medium was shown to retard virus replication in a dose-dependent fashion, although a complete inhibitory effect was not seen with any clinically attainable concentration of drug. Exposure of HIV-1-inoculated cells to AZT did not give rise to progeny virus possessing a drug-resistant phenotype. However, the study of clonal derivatives of U-937 cells revealed cellular variants with increased susceptibility to HIV-1, and against which AZT had reduced effectiveness in comparison with the parental line. No effect of AZT was seen on cells already infected by HIV-1, suggesting that this drug had no influence on viral replication in U-937 cells into which viral DNA had previously integrated.
Boulerice
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F
Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
Wainberg
M A
MA
D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D014644:Genetic Variation; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000382:microbiology / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000382:microbiology; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*
D015215:Zidovudine; D006854:Hydrocortisone