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Journal of Virology, March 2006, p. 2380-2389, Vol. 80, No. 5
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.5.2380-2389.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Modeling and Estimation of Replication Fitness of Human Immunodeficiency Virus Type 1 In Vitro Experiments by Using a Growth Competition Assay

Hulin Wu,1* Yangxin Huang,2 Carrie Dykes,3 Dacheng Liu,1 Jingming Ma,1 Alan S. Perelson,4 and Lisa M. Demeter3

Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 630, Rochester, New York 14642,1 Department of Epidemiology & Biostatistics, College of Public Health, MDC 56, University of South Florida, 13201 Bruce B. Downs Blvd., Tampa, Florida 33612,2 Department of Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 689, Rochester, New York 14642,3 Theoretical Biology & Biophysics Group, MS-K710, T-10, Los Alamos National Laboratory, Los Alamos, New Mexico 875454

Received 14 June 2005/ Accepted 2 December 2005

Growth competition assays have been developed to quantify the relative fitnesses of human immunodeficiency virus (HIV-1) mutants. In this article we develop mathematical models to describe viral/cellular dynamic interactions in the assay experiment, from which new competitive fitness indices or parameters are defined. These indices include the log fitness ratio (LFR), the log relative fitness (LRF), and the production rate ratio (PRR). From the population genetics perspective, we clarify the confusion and correct the inconsistency in the definition of relative fitness in the literature of HIV-1 viral fitness. The LFR and LRF are easier to estimate from the experimental data than the PRR, which was misleadingly defined as the relative fitness in recent HIV-1 research literature. Calculation and estimation methods based on two data points and multiple data points were proposed and were carefully studied. In particular, we suggest using both standard linear regression (method of least squares) and a measurement error model approach for more-accurate estimates of competitive fitness parameters from multiple data points. The developed methodologies are generally applicable to any growth competition assays. A user-friendly computational tool also has been developed and is publicly available on the World Wide Web at http://www.urmc.rochester.edu/bstools/vfitness/virusfitness.htm.

* Corresponding author. Mailing address: Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 630, Rochester, New York 14642. Phone: (585) 275-6767. Fax: (585) 273-1031. E-mail: hwu{at}bst.rochester.edu.

Journal of Virology, March 2006, p. 2380-2389, Vol. 80, No. 5
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.5.2380-2389.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dykes, C., Demeter, L. M. (2007). Clinical Significance of Human Immunodeficiency Virus Type 1 Replication Fitness. Clin. Microbiol. Rev. 20: 550-578 [Abstract] [Full Text]  
  • Dykes, C., Wang, J., Jin, X., Planelles, V., An, D. S., Tallo, A., Huang, Y., Wu, H., Demeter, L. M. (2006). Evaluation of a multiple-cycle, recombinant virus, growth competition assay that uses flow cytometry to measure replication efficiency of human immunodeficiency virus type 1 in cell culture.. J. Clin. Microbiol. 44: 1930-1943 [Abstract] [Full Text]  


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