Biomaterial Database

Sindbis virus mutants resistant to mycophenolic acid and ribavirin. 1987

L M Scheidel, and R K Durbin, and V Stollar

Previous work from this laboratory has demonstrated a correlation between the inhibition by ribavirin (Rbv), mycophenolic acid (MPA), or 2-amino thiadiazole (TDA) of Sindbis virus replication in Aedes albopictus mosquito cells and a reduction in cellular GTP levels. This reduction in GTP results from the inhibition by these drugs of inosine monophosphate dehydrogenase (IMPDH), the first enzyme specific for the de novo synthesis of GMP. By serial passage of SV in A. albopictus cells in the presence of 25 microM MPA, we have now isolated viral mutants which are highly resistant not only to MPA but also to Rbv and TDA. For example, whereas 500 microM Rbv reduced the plaquing efficiency of SVSTD by at least 10(6)-fold, the same concentration of Rbv reduced the plaquing efficiency of the MPA-resistant mutants less than 5-fold. This is the first example of a viral mutant resistant to the antiviral compound Rbv.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D009173	Mycophenolic Acid	Compound derived from Penicillium stoloniferum and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase (IMP DEHYDROGENASE). Mycophenolic acid exerts selective effects on the immune system in which it prevents the proliferation of T-CELLS, LYMPHOCYTES, and the formation of antibodies from B-CELLS. It may also inhibit recruitment of LEUKOCYTES to sites of INFLAMMATION.	Cellcept,Mycophenolate Mofetil,Mycophenolate Mofetil Hydrochloride,Mycophenolate Sodium,Mycophenolic Acid Morpholinoethyl Ester,Myfortic,RS 61443,RS-61443,Sodium Mycophenolate,Mofetil Hydrochloride, Mycophenolate,Mofetil, Mycophenolate,Mycophenolate, Sodium,RS61443
D009713	Nucleotidyltransferases	A class of enzymes that transfers nucleotidyl residues. EC 2.7.7.	Nucleotidyltransferase
D002999	Clone Cells	A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)	Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D004352	Drug Resistance, Microbial	The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).	Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D006160	Guanosine Triphosphate	Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.	GTP,Triphosphate, Guanosine
D000330	Aedes	A genus of mosquitoes (CULICIDAE) frequently found in tropical and subtropical regions. YELLOW FEVER and DENGUE are two of the diseases that can be transmitted by species of this genus.	Aede
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012254	Ribavirin	A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses.	Ribovirin,Tribavirin,ICN-1229,Rebetol,Ribamide,Ribamidil,Ribamidyl,Ribasphere,Vilona,Viramide,Virazide,Virazole,ICN 1229,ICN1229
D012263	Ribonucleosides	Nucleosides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)