Modeling within-host evolution of HIV: mutation, competition and strain replacement.
Virus evolution during infection of a single individual is a well-known feature of disease progression in chronic viral diseases. However, the simplest models of virus competition for host resources show the existence of a single dominant strain that grows most rapidly during the initial period of infection and competitively excludes all other virus strains. Here, we examine the dynamics of strain replacement in a simple model that includes a convex trade-off between rapid virus reproduction and long-term host cell survival. Strains are structured according to their within-cell replication rate. Over the course of infection, we find a progression in the dominant strain from fast- to moderately-replicating virus strains featuring distinct jumps in the replication rate of the dominant strain over time. We completely analyze the model and provide estimates for the replication rate of the initial dominant strain and its successors. Our model lays the groundwork for more detailed models of HIV selection and mutation. We outline future directions and application of related models to other biological situations.
Ball
Colleen L
CL
Department of Mathematics and Institute of Applied Mathematics, University of British Columbia, 1984 Mathematics Road, Vancouver, BC, V6T 1Z2, Canada.
Gilchrist
Michael A
MA
Coombs
Daniel
D
D000465:Algorithms; D016923:Cell Death; D003198:Computer Simulation; D019143:Evolution, Molecular; D005838:Genotype; D006678:HIV / Q000235:genetics* / Q000254:growth & development; D015658:HIV Infections / Q000097:blood / Q000821:virology*; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D017354:Point Mutation; D012641:Selection, Genetic; D013601:T-Lymphocytes / Q000473:pathology / Q000821:virology; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics