title: A mathematical model of HIV dynamics in the presence of a rescuing virus with replication deficiency.
abstract: Recently, an enzyme (Cre recombinase) has been developed by directed evolution that successfully removes the HIV genome from the nuclear DNA of infected cells. To explore this idea further, we hypothesized that a replication deficient virus (called "police virus"), added externally, can deliver such a recombinase which excises the integrated HIV DNA from the genome of infected cells. Such a "police virus" could attack and remove the integrated provirus which is not possible using contemporary strategies. The hypothesis was tested by developing a mathematical model that describes the dynamics of virus-host cell interaction and the consequences of introducing the "police virus". The simulations show that such a therapeutic vector may eradicate all HIV viruses from the system in the long term. All components of the HIV infection (free virus, latently, and actively infected cells) can be cleared and the system ends up only with susceptible CD4+ cells. The proposed model may provide new insights in the dynamical behavior and future alternative treatments of HIV.
authors.affiliation: Department of Biomathematics, University of Thessaly School of Medicine, 2 Biopolis Str, Larissa 41110, Greece. zintza@med.uth.gr
authors.forename: Elias
authors.initials: E
authors.lastname: Zintzaras
authors.forename: Axel
authors.initials: A
authors.lastname: Kowald
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002467:Cell Nucleus / Q000378:metabolism; D003198:Computer Simulation; D004247:DNA / Q000235:genetics; D016679:Genome, Viral; D006678:HIV / Q000502:physiology*; D006801:Humans; D019426:Integrases / Q000235:genetics; D008954:Models, Biological; D008962:Models, Theoretical; D016296:Mutagenesis; D012984:Software; D014779:Virus Replication
chemical_list: D004247:DNA; C045073:Cre recombinase; D019426:Integrases