A hybrid stochastic-deterministic computational model accurately describes spatial dynamics and virus diffusion in HIV-1 growth competition assay.
We present a new hybrid stochastic-deterministic, spatially distributed computational model to simulate growth competition assays on a relatively immobile monolayer of peripheral blood mononuclear cells (PBMCs), commonly used for determining ex vivo fitness of human immunodeficiency virus type-1 (HIV-1). The novel features of our approach include incorporation of viral diffusion through a deterministic diffusion model while simulating cellular dynamics via a stochastic Markov chain model. The model accounts for multiple infections of target cells, CD4-downregulation, and the delay between the infection of a cell and the production of new virus particles. The minimum threshold level of infection induced by a virus inoculum is determined via a series of dilution experiments, and is used to determine the probability of infection of a susceptible cell as a function of local virus density. We illustrate how this model can be used for estimating the distribution of cells infected by either a single virus type or two competing viruses. Our model captures experimentally observed variation in the fitness difference between two virus strains, and suggests a way to minimize variation and dual infection in experiments.
Department of Mathematics, Case Western Reserve University, 10900 Euclid Avenue, Yost Hall Room 200, Cleveland, Ohio 44106, United States of America; Theoretical Biology and Biophysics, MS K710, T-6, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States of America. Electronic address: tti@case.edu.
Taina
T
Immonen
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, 2109 Adelbert Road, BRB1034, Cleveland, Ohio 44106, United States of America. Electronic address: rxg26@case.edu.
Richard
R
Gibson
Theoretical Biology and Biophysics, MS K710, T-6, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States of America. Electronic address: tkl@lanl.gov.
Thomas
T
Leitner
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, 2109 Adelbert Road, BRB1034, Cleveland, Ohio 44106, United States of America. Electronic address: maf60@case.edu.
Melanie A
MA
Miller
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, 2109 Adelbert Road, BRB1034, Cleveland, Ohio 44106, United States of America. Electronic address: eja3@case.edu.
Eric J
EJ
Arts
Department of Mathematics, Case Western Reserve University, 10900 Euclid Avenue, Yost Hall Room 200, Cleveland, Ohio 44106, United States of America. Electronic address: ejs49@case.edu.
Erkki
E
Somersalo
Department of Mathematics, Case Western Reserve University, 10900 Euclid Avenue, Yost Hall Room 200, Cleveland, Ohio 44106, United States of America. Electronic address: dxc57@case.edu.
Daniela
D
Calvetti
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008390:Markov Chains; D018448:Models, Immunological