Immune impairment in HIV infection: existence of risky and immunodeficiency thresholds.
Results of several studies show that some DC populations are susceptible to HIV. Modulation of DCs by HIV infection, in particular interference of the antigen-presenting function of DCs, is a key aspect in viral pathogenesis and contributes to viral evasion from immunity because the loss of the DC function engenders some impairment effects for a proliferation of CTL responses, which play an important role in the immune response to HIV. As described herein, we use a simple mathematical model to examine virus-immune dynamics over the course of HIV infection in the context of the immune impairment effects. A decrease of the DC number and function during the course of HIV-1 infection is observed. Therefore, we simply assumed that the immune impairment rate increases over the HIV infection. Under the assumption, four processes of the disease progression dynamics of our model are classifiable according to their virological properties. It is particularly interesting a typical disease progression presents a "risky threshold" and an "immunodeficiency threshold". Regarding the former, the immune system might collapse when the impairment rate of HIV exceeds a threshold value (which corresponds to a transcritical bifurcation point). For the latter, the immune system always collapses when the impairment rate exceeds the value (which corresponds to a saddle-node bifurcation point). To test our theoretical framework, we investigate the existence and distribution of these thresholds in 10 patients.
Iwami
Shingo
S
Graduate School of Science and Technology, Shizuoka University, Japan. dsiwami@ipc.shizuoka.ac.jp
Miura
Tomoyuki
T
Nakaoka
Shinji
S
Takeuchi
Yasuhiro
Y
D003713:Dendritic Cells / Q000276:immunology; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D018448:Models, Immunological; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology