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Model with two types of CTL regulation and experiments on CTL dynamics.

TitleModel with two types of CTL regulation and experiments on CTL dynamics.
Publication TypeJournal Article
Year of Publication2010
AuthorsSergeev, RA, Batorsky, RE, IM Rouzine
JournalJ Theor Biol
Volume263
Issue3
Pagination369-84
Date Published2010 Apr 07
ISSN1095-8541
KeywordsAnimals, Anti-HIV Agents, Cell Differentiation, HIV, HIV Infections, Humans, Macaca, Models, Biological, Simian Acquired Immunodeficiency Syndrome, T-Lymphocytes, Cytotoxic, Virus Replication
Abstract

Recently, we developed a mathematical model of interaction between the HIV and the immune system to match various dynamic experiments carried out in HIV-infected humans and SIV-infected macaques. The model includes helper cell-dependent and helper cell-independent cytotoxic lymphocytes (CTLs) and predicts two stable steady states, a state with a high virus load and few helper cells, and another state with a low virus load and many helper cells. Here we upgrade the model to take into account recent reports on the link between the activation status of infected cells and their ability to produce virus, the effect of helper cells at the time of priming on CTL differentiation, and virus dynamics in unvaccinated macaques with a broad genetic background acutely infected with SIVmac251. We also discuss in detail the experimental justification of the CTL block and the robustness of model predictions with respect to the hypothesis of two CTL subtypes.

DOI10.1016/j.jtbi.2009.11.003
Alternate JournalJ. Theor. Biol.
PubMed ID19913558
PubMed Central IDPMC2827655
Grant ListR01 AI063926 / AI / NIAID NIH HHS / United States
R01 AI063926-03 / AI / NIAID NIH HHS / United States
T5R01AI063926 / AI / NIAID NIH HHS / United States