Effect of Ribavirin on Hela Cells ExpressingE. coliXanthine-Guanine Phosphoribosyl Transferase
| Autor: | Byron K. Murray, Douglas O. Andersen, James A. North |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
0301 basic medicine
biology Guanine viruses Ribavirin 030106 microbiology Guanosine General Medicine biology.organism_classification 01 natural sciences Virology Virus 0104 chemical sciences HeLa Xanthine phosphoribosyltransferase 010404 medicinal & biomolecular chemistry 03 medical and health sciences chemistry.chemical_compound chemistry IMP dehydrogenase Vesicular stomatitis virus |
| Zdroj: | Antiviral Chemistry and Chemotherapy. 4:249-252 |
| ISSN: | 2040-2066 |
| DOI: | 10.1177/095632029300400409 |
| Popis: | Summary HeLa cells expressing the E. coli gene Ecogpt and cultured with xanthine were extremely resistant to antiproliferation by mycophenolic acid, but were only partially resistant to the effects of ribavlrln, Nucleotide analyses of these transfected cells, and;,the parental HeLa cells, demonstrated an assoclatldn between the GTP/ribavirin triphosphate ratio and virus yield reductions. The antiviral mechanism of ribavirin (1-I3-D-ribofuranosyl 1,2,4-triazole-3-carboxamide), a guanosine analogue that inhibits a broad range of DNA and RNA viruses, continues to be elusive. It has been established that ribavirin monophosphate (RMP) inhibits inosine monophosphate dehydrogenase (IMPDH; K;= 2.5 x 10- 7 M) and depletes the intracellular GTP pool (Streeter et sl., 1973; Malinoski and Stollar, 1981; Stridh, 1983). It has been suggested that this depletion indirectly suppresses viral nucleic acid synthesis (Streeter et aI., 1973). Another compound, mycophenolic acid (MPA), while structurally unrelated to ribavirin, has been characterized as a prototypic IMPDH inhibitor with K; = 3 x 10- 8 M (Franklin and Cook, 1969). However, studies performed recently in our laboratory demonstrate that in combination, MPA and ribavirin act in a synergistic manner to reduce yields of parainfluenza virus type 3 (Para-3) and vesicular stomatitis virus 0/Sv) in infected human epithelioid cervical carcinoma (HeLa) cells, suggesting that ribavirin inhibits virus replication by a mechanism distinct from IMPDH inhibition (data not shown). |
| Databáze: | OpenAIRE |
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