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Mutants of feline immunodeficiency virus resistant to 3'-azido-3'-deoxythymidine. 1991

K M Remington, and B Chesebro, and K Wehrly, and N C Pedersen, and T W North
Division of Biological Sciences, University of Montana, Missoula 59812.

We selected 3'-azido-3'-deoxythymidine (AZT)-resistant mutants of feline immunodeficiency virus (FIV) in a cat cell culture system. The characterization of one of these mutants was facilitated by the development of a focal immunoassay which could accurately measure FIV infectivity. This assay was used to quantitate the susceptibility of FIV to various inhibitors. The AZT-resistant mutant was found to be cross-resistant to 3'-azido-2',3'-dideoxyuridine and 3'-azido-2',3'-dideoxyguanosine but remained sensitive to several other inhibitors (2',3'-dideoxyinosine, 2',3'-dideoxy-2',3'-didehydrothymidine, and phosphonoformate). These patterns of cross-resistance and sensitivity were similar to those of the AZT-resistant human immunodeficiency virus (HIV) that has recently been isolated from patients with AIDS (B. A. Larder and S. D. Kemp, Science 246:1155-1158, 1989). Like the AZT-resistant HIV, purified reverse transcriptase from mutant FIV failed to show resistance to the 5'-triphosphate of AZT. This mutant can be used in the FIV model system to study the mechanisms of drug resistance and to determine the pathogenicity of AZT-resistant mutants.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
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
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, 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
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
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D015215 Zidovudine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U
D016089 Immunodeficiency Virus, Feline A species of LENTIVIRUS, subgenus feline lentiviruses (LENTIVIRUSES, FELINE) isolated from cats with a chronic wasting syndrome, presumed to be immune deficiency. There are 3 strains: Petaluma (FIP-P), Oma (FIP-O) and Puma lentivirus (PLV). There is no antigenic relationship between FIV and HIV, nor does FIV grow in human T-cells. FIV,FTLV,Feline Immunodeficiency Virus,Feline T-Lymphotropic Lentivirus,Lentivirus, Puma,Puma lentivirus,Feline T-Lymphotropic Virus,Feline Immunodeficiency Viruses,Feline T Lymphotropic Lentivirus,Feline T Lymphotropic Virus,Lentivirus, Feline T-Lymphotropic,T-Lymphotropic Lentivirus, Feline,T-Lymphotropic Virus, Feline

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