The race between initial T-helper expansion and virus growth upon HIV infection influences polyclonality of the response and viral set-point

H. Korthals Altes*, R. M. Ribeiro, R. J. De Boer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1349-1358
Number of pages10
JournalProceedings of the Royal Society B: Biological Sciences
Volume270
Issue number1522
DOIs
Publication statusPublished - 7 Jul 2003

Keywords

  • CD4 T help
  • HIV
  • Mathematical model
  • Polyclonality
  • Viral set-point

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