Infection dynamics in HIV-specific CD4 T cells: does a CD4 T cell boost benefit the host or the virus?
Recent experimental data have shown that HIV-specific CD4 T cells provide a very important target for HIV replication. We use mathematical models to explore the effect of specific CD4 T cell infection on the dynamics of virus spread and immune responses. Infected CD4 T cells can provide antigen for their own stimulation. We show that such autocatalytic cell division can significantly enhance virus spread, and can also provide an additional reservoir for virus persistence during anti-viral drug therapy. In addition, the initial number of HIV-specific CD4 T cells is an important determinant of acute infection dynamics. A high initial number of HIV-specific CD4 T cells can lead to a sudden and fast drop of the population of HIV-specific CD4 T cells which results quickly in their extinction. On the other hand, a low initial number of HIV-specific CD4 T cells can lead to a prolonged persistence of HIV-specific CD4 T cell help at higher levels. The model suggests that boosting the population of HIV-specific CD4 T cells can increase the amount of virus-induced immune impairment, lead to less efficient anti-viral effector responses, and thus speed up disease progression, especially if effector responses such as CTL have not been sufficiently boosted at the same time.
Wodarz
Dominik
D
Department of Ecology and Evolutionary Biology, 321 Steinhaus Hall, University of California, Irvine, CA 92697, USA. dwodarz@uci.edu
Hamer
Dean H
DH
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003198:Computer Simulation; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D018448:Models, Immunological; D014779:Virus Replication / Q000276:immunology