Effect of Ribavirin on Protein and RNA Synthesis in VEE Virus-Infected Cells.
Abstract
Ribavirin is a nucleoside analogue with antiviral activity against the etiologic agents of such militarily important diseases as Lassa fever, Bolivian and Argentinian hemorrhagic fevers, Rift Valley fever, and Venezuelan equine encephalomyelitis (VEE). Use of antiviral drugs in military personnel, however, requires a comprehensive understanding of their pharmacology to ensure selection of the correct drug which combines low toxicity and high efficacy for treating specific virus infections. To this end, we studied the mechanism by which ribavirin regulates the replication of VEE virus grown in vitro in BHK-21 cells. The following observations were made: (1) Ribavirin (50-300 micro/ml) inhibited virus growth by more than 90%; (2) The replication of viral genome was not inhibited by ribavirin; (3) Chromatography of polynucleotides obtained by treatment of tritium guano-since-labeled mRNA with ribonuclease, showed a peak with the same profile as ppp7mG 'cap' standard. The magnitude of the peak was reduced or absent from mRNA preparations isolated from virus-infected cells treated with ribavirin; and (4) mRNA isolated from ribavirin-treated infected cells was less efficient in its capacity to direct protein synthesis in an in vitro translation system. These observations show that ribavirin interferes with translation of viral messenger by replacing or inhibiting formation of the cap structure on viral RNA genome.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 11, 1980
- Accession Number
- ADA084699
Entities
People
- Edward L. Stephen
- James S. Little
- Peter B. Jahrling
- Peter G. Canonico
Organizations
- United States Army Medical Research Institute of Infectious Diseases