The race between initial T-helper expansion and virus growth upon HIV infection influences polyclonality of the response and viral set-point
| Autor: | R.J. de Boer, H. Korthals Altes, Ruy M. Ribeiro |
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| Přispěvatelé: | Theoretical Ecology (IBED, FNWI) |
| Rok vydání: | 2003 |
| Předmět: |
Clone (cell biology)
HIV Infections viral set-point Biology Virus Replication Models Biological General Biochemistry Genetics and Molecular Biology Virus Epitope Immune system CD4 T help Humans Avidity General Environmental Science General Immunology and Microbiology HIV T-Lymphocytes Helper-Inducer General Medicine Viral Load Virology Viral replication polyclonality Immunology HIV-1 General Agricultural and Biological Sciences Biologie Viral load mathematical model CD8 Research Article |
| Zdroj: | Proceedings of the Royal Society B-Biological Sciences, 270(1522), 1349-1358. Royal Society of London Proceedings. Biological sciences / The Royal Society, 270, 1349. Royal Society of London |
| ISSN: | 1471-2954 0962-8452 |
| Popis: | Infection with HIV is characterized by very diverse disease-progression patterns across patients, associated with a wide variation in viral set-points. Progression is a multifactorial process, but an important role has been attributed to the HIV-specific T-cell response. To explore the conditions under which different set-points may be explained by differences in initial CD4 and CD8 T-cell responses and virus inoculum, we have formulated a model assuming that HIV-specific CD4 cells are both targets for infection and mediators of a monoclonal or polyclonal immune response. Clones differ in functional avidity for HIV epitopes. Importantly, in contrast to previous models, in this model we obtained coexistence of multiple clones at steady-state viral set-point, as seen in HIV infection. We found that, for certain parameter conditions, multiple steady states are possible: with few initial CD4 helper cells and high virus inoculum, no immune response is established and target-cell-limited infection follows, with associated high viral load; when CD4 clones are initially large and virus inoculum is low, infection can be controlled by several clones. The conditions for the dependence of viral set-point on initial inoculum and CD4 T-helper clone availability are investigated in terms of the effector mechanism of the clones involved. |
| Databáze: | OpenAIRE |
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