This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Remington, K M Articles by North, T W Search for Related Content PubMed PubMed Citation Articles by Remington, K M Articles by North, T W

 Previous Article  |  Next Article 

J Virol. 1994 February; 68(2): 632-637

Rapid phenotypic reversion of zidovudine-resistant feline immunodeficiency virus without loss of drug-resistant reverse transcriptase.

Division of Biological Sciences, University of Montana, Missoula 59812.

ABSTRACT

We have selected and plaque purified zidovudine (3'-azido-3'-deoxythymidine [AZT])-resistant mutants from an infectious molecular clone of feline immunodeficiency virus (FIV). The patterns of cross-resistance and drug susceptibilities of these mutants were similar to those of the AZT-resistant FIV that we previously selected in vitro from a wild-type FIV population and to those of the most common AZT-resistant clinical isolates of human immunodeficiency virus type 1. Two AZT-resistant mutants of FIV, one selected from a normal population and one selected from the molecular clone, each reverted rapidly to an AZT-sensitive phenotype when passaged in the absence of drug. Sequence analysis of the reverse transcriptase (RT)-encoding region from the plaque-purified AZT-resistant FIV revealed a single base change at position 2939, resulting in a Glu-to-Lys substitution at amino acid 202 of the RT. Similar analyses of plaque-purified revertants showed that the phenotypic reversion was not the result of a genotypic reversion at this position and that no additional mutations existed within the RT-encoding region of the revertants. Moreover, RTs purified from the mutant and revertant were both resistant to the 5'-triphosphate of AZT. These results indicate the complexity of AZT resistance and suggest the presence of additional factors, outside the RT-encoding region, which may contribute to AZT resistance.

This article has been cited by other articles:

• Saenz, D. T., Teo, W., Olsen, J. C., Poeschla, E. M. (2005). Restriction of Feline Immunodeficiency Virus by Ref1, Lv1, and Primate TRIM5{alpha} Proteins. J. Virol. 79: 15175-15188 [Abstract] [Full Text]  
• Klarmann, G. J., Smith, R. A., Schinazi, R. F., North, T. W., Preston, B. D. (2000). Site-specific Incorporation of Nucleoside Analogs by HIV-1 Reverse Transcriptase and the Template Grip Mutant P157S. TEMPLATE INTERACTIONS INFLUENCE SUBSTRATE RECOGNITION AT THE POLYMERASE ACTIVE SITE. J. Biol. Chem. 275: 359-366 [Abstract] [Full Text]  
• Smith, R. A., Klarmann, G. J., Stray, K. M., von Schwedler, U. K., Schinazi, R. F., Preston, B. D., North, T. W. (1999). A New Point Mutation (P157S) in the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 Confers Low-Level Resistance to (-)-beta -2',3'-Dideoxy-3'-Thiacytidine. Antimicrob. Agents Chemother. 43: 2077-2080 [Abstract] [Full Text]  
• Smith, R. A., Remington, K. M., Preston, B. D., Schinazi, R. F., North, T. W. (1998). A Novel Point Mutation at Position 156 of Reverse Transcriptase from Feline Immunodeficiency Virus Confers Resistance to the Combination of (-)-beta -2',3'-Dideoxy-3'-Thiacytidine and 3'-Azido-3'-Deoxythymidine. J. Virol. 72: 2335-2340 [Abstract] [Full Text]