Model of HIV-1 disease progression based on virus-induced lymph node homing and homing-induced apoptosis of CD4+ lymphocytes.
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/mm3 of blood to roughly 100/mm3 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.
Kirschner
D
D
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, Michigan, USA. kirschne@umich.edu
Webb
G F
GF
Cloyd
M
M
D019380:Anti-HIV Agents / Q000627:therapeutic use; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002465:Cell Movement; D015658:HIV Infections / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D015497:HIV-1; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008954:Models, Biological
D019380:Anti-HIV Agents