Microtubule-depolymerizing agents inhibit Moloney murine leukaemia virus production.

The effects of microtubule-depolymerizing agents on virion production in MJD-54 cells chronically infected with Moloney murine leukaemia virus were examined. By measuring the amount of reverse transcriptase activity remaining in particles recovered from culture fluids, we found that incubation with 1 microM- or 10 microM-colchicine, vinblastine or nocodazole resulted in 30 to 40% decreases in virus production. The decrease in virus production did not seem to be due to general damage to the cells since cellular RNA and protein synthesis were only slightly, if at all, inhibited by the drug treatment (less than 10%). Furthermore, virus proteins accumulated inside drug-treated cells, viz, [35S]methionine-labelled Pr65gag showed a 1.5-fold increase over a 3 h continuous label interval. Consistent with this accumulation of virus protein, electron microscope studies showed that inside drug-treated cells ther was a 2- to 2.5-fold accumulation of virions within cytoplasmic vesicles. All of these results support the idea that cytoplasmic microtubules play a role in the production of murine leukaemia virus.