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Two types of cytotoxic lymphocyte regulation explain kinetics of immune response to human immunodeficiency virus.

TitleTwo types of cytotoxic lymphocyte regulation explain kinetics of immune response to human immunodeficiency virus.
Publication TypeJournal Article
Year of Publication2006
AuthorsIM Rouzine, Sergeev, RA, Glushtsov, AI
JournalProc Natl Acad Sci U S A
Volume103
Issue3
Pagination666-71
Date Published2006 Jan 17
ISSN0027-8424
KeywordsAnimals, Anti-Retroviral Agents, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Computer Simulation, HIV, HIV Infections, Humans, Kinetics, Lymphocyte Activation, Macaca mulatta, Models, Immunological, Simian Immunodeficiency Virus, T-Lymphocytes, Cytotoxic
Abstract

The organization of the cytotoxic T lymphocyte (CTL) response at organismal level is poorly understood. We propose a mathematical model describing the interaction between HIV and its host that explains 20 quantitative observations made in HIV-infected individuals and simian immunodeficiency virus-infected monkeys, including acute infection and response to various antiretroviral therapy regimens. The model is built on two modes of CTL activation: direct activation by infected cells and indirect activation by CD4 helper cells activated by small amounts of virus. Effective infection of helper cells by virus leads to a stable chronic infection at high virus load. We assume that CTLs control virus by killing infected cells. We explain the lack of correlation between the CTL number and the virus decay rate in therapy and predict that individuals with a high virus load can be switched to a low-viremia state that will maintain stability after therapy, but the switch requires fine adjustment of therapy regimen based on the model and individual parameters.

DOI10.1073/pnas.0510016103
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID16407101
PubMed Central IDPMC1334670
Grant ListK25 AI001811 / AI / NIAID NIH HHS / United States
K25AI01811 / AI / NIAID NIH HHS / United States