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Updated: May 17, 2026
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Pairwise Growth Competition Assay for Determining the Replication Fitness of Human Immunodeficiency Viruses
Published on: May 4, 2015
Interrelationship between HIV-1 fitness and mutation rate
Michael J Dapp1, Richard H Heineman, Louis M Mansky
1Institute for Molecular Virology, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, USA.
Journal of Molecular Biology
|October 23, 2012
Summary
Human immunodeficiency virus type 1 (HIV-1) mutation rates are heritable and influenced by natural selection. Studies show that altering HIV-1 reverse transcriptase (RT) fidelity impacts viral fitness, with both higher and lower fidelity correlating with reduced fitness.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Virus mutation rates are heritable and subject to natural selection.
- Human immunodeficiency virus type 1 (HIV-1) is an advantageous model for studying mutation rate optimization due to extensive data on its reverse transcriptase (RT).
Purpose of the Study:
- To analyze the relationship between mutation rate and viral fitness in HIV-1.
- To investigate the effects of specific RT mutants on viral fidelity and fitness.
Main Methods:
- A panel of 10 HIV-1 RT mutants, many with drug resistance, was analyzed.
- Viral fidelity was measured using single-cycle vector assays.
- Viral fitness was assessed through ex vivo head-to-head competition assays.
Main Results:
- Mutants with altered fidelity (higher or lower) exhibited a corresponding decrease in viral fitness.
- The study observed a higher prevalence of mutator phenotypes compared to antimutator phenotypes in the tested virus panel.
- An interrelationship between HIV-1 fitness and mutation rate was established.
Conclusions:
- Mutator and antimutator phenotypes in HIV-1 are associated with reduced viral fitness.
- Replication fidelity in viruses may come at the cost of replication kinetics.
- Findings support models explaining why retroviruses and RNA viruses maintain fidelity near the extinction threshold.
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