Mode of Action of 5-Azacytidine on Arboviruses
FORT DETRICK FREDERICK MD
Pagination or Media Count:
Using eastern equine encephalitis EEE virus or Ets-4 a temperature-sensitive mutant of EEE in pulse-labeled experiments, 5-AzaC did not show any significant effect on the initiation or rate of total RNA synthesis but did lower the cumulative uptake of C14-uridine in 6-hour infected cells. The lower cumulative uptake may be the result of breakdown of RNA synthesized in the presence of 5-AzaC as hypothesized for bacteria. Sucrose gradient analysis of the different viral RNA species in infected cells revealed a somewhat diminished 20S and 27S RNA fraction in 6-hour infected cultures treated with 25 microgram ml 5-AzaC but the 45S fraction was not affected. The viral RNA synthesized in the presence of 5-AzaC was significantly labile upon phenol extraction, having only 2 to 5 of the infectivity of controls, yet it showed approximately the same quantity of 45S RNA the latter is normally the most infectious of the known species of viral RNA. The data accumulated on the mutagenic and inhibitory effects of 5-AzaC suggest that it acts directly on viral RNA and support the notion yet to be proved that it is incorporated into the viral RNA.
- Chemical, Biological and Radiological Warfare