Model of HIV-1 Disease Progression Based on Virus-Induced Lymph Node Homing and Homing-Induced Apoptosis of CD4+ Lymphocytes

Abstract

Several proposed theories have described the progression of HIV infection. Even so, no concrete evidence supports any as comprehensive, including, for example, why the CD4+ T-cell counts fall from 1000/mm^3 of blood to roughly 100/mm^3 over an average 10-year period, whereas concomitant viral loads are relatively constant, increasing by several orders of magnitude in late-stage disease. Here, we develop and validate a theoretical model that altered lymphocyte circulation patterns between the lymph system and blood due to HIV-induced enhanced lymph-node homing and subsequent apoptosis of resting CD4+ T cells can explain many aspects of HIV-1 disease progression. These results lead to a recalculation of the CD4+ lymphocyte dynamics during highly active antiretroviral therapy, and also suggest new targets for therapy.