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Updated: Aug 15, 2026
Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
Published on: June 16, 2011
The mutation frequency of feline immunodeficiency virus enhanced by 3'-azido-3'-deoxythymidine
R A LaCasse1, K M Remington, T W North
1Division of Biological Sciences, University of Montana, Missoula, 59812, USA.
Abstract:
We have developed a host range system to measure the mutation frequency of feline immunodeficiency virus (FIV), the feline homologue of human immunodeficiency virus type 1 (HIV-1). When wild-type FIV was grown in the presence of a known mutagen, 5-bromo-2'-deoxyuridine (BUdR), a dose-dependent increase of host range mutants was detected. Using this system, we have evaluated the effects of antiviral drugs upon the mutation frequency of FIV. Subinhibitory concentrations of 3'-azido-3'-deoxythymidine (AZT), the most common antiviral drug used in AIDS chemotherapy, increased the mutation frequency of FIV in a dose-dependent manner. Two other antivirals, 2',3'-dideoxyinosine (ddI) and 2'3'-dideoxycytidine (ddC), did not show this effect.
Insights
A new feline immunodeficiency virus (FIV) host range system revealed that the antiviral drug AZT increases FIV mutation frequency. Other tested antivirals, ddI and ddC, did not affect FIV mutation rates.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- Feline immunodeficiency virus (FIV) is a model lentivirus, analogous to human immunodeficiency virus type 1 (HIV-1).
- Measuring mutation frequency is crucial for understanding viral evolution and drug resistance.
- Existing methods for assessing FIV mutation rates are limited.
Purpose of the Study:
- To develop and validate a novel host range system for quantifying FIV mutation frequency.
- To evaluate the impact of antiviral drugs on FIV mutation rates.
- To assess the mutagenic potential of specific antiretroviral agents.
Main Methods:
- Development of a FIV host range assay.
- Exposure of wild-type FIV to a known mutagen, 5-bromo-2'-deoxyuridine (BUdR).
- Treatment of FIV with subinhibitory concentrations of antiviral drugs: 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI), and 2'3'-dideoxycytidine (ddC).
- Quantification of host range mutants to determine mutation frequency.
Main Results:
- The developed host range system successfully detected a dose-dependent increase in FIV host range mutants upon exposure to BUdR.
- Subinhibitory concentrations of AZT significantly increased FIV mutation frequency in a dose-dependent manner.
- The antiviral drugs ddI and ddC did not demonstrate a significant effect on FIV mutation frequency at the tested concentrations.
Conclusions:
- The novel FIV host range system is effective for measuring mutation frequency.
- AZT, at subinhibitory concentrations, acts as a mutagen for FIV, increasing its mutation rate.
- This finding has implications for FIV management and understanding lentiviral drug interactions.
