The race between initial T-helper expansion and virus growth upon HIV infection influences polyclonality of the response and viral set-point.
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.
Korthals Altes
H
H
Laboratoire d'Immunologie Cellulaire et Tissulaire, Hôpital Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75013 Paris, France. altes@science.uva.nl
Ribeiro
R M
RM
de Boer
R J
RJ
D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000821:virology*; D019562:Viral Load; D014779:Virus Replication