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.

Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-γ in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome

“…22,53,54 The data presented here on the effects of SIV infection in lymphoid tissues of rhesus macaques are consistent with such a model, although the CXCR3 ϩ T lymphocytes we propose as being important in these processes are likely effector T lymphocytes. Consistent with these models, the biphasic increase in CD4 ϩ T lymphocyte counts observed in patients after potent antiretroviral therapy 55 might be due partly to coordinated reductions in expression of IFN-␥ and CXCL9/Mig.…”

A Model to Predict Cell-Mediated Immune Regulatory Mechanisms During Human Infection withMycobacterium tuberculosis

“…Future studies will specifically investigate the role of this spatial component, and a two-compartment model (lymph node and lung) including the role of dendritic cells and Th0 cells in the lymph node is anticipated. Compartmental models of the lymph system and blood have contributed to a greater understanding of AIDS progression in pediatric patients (88) as well as progression of HIV in adults (89).…”

Optimal HIV treatment by maximising immune response

“…The exact mechanism by which this occurs remains unknown, but several models have been suggested. For a variety of different hypotheses of how this occurs, we refer the reader to papers by Weber and Weiss [27], Nowak and May [21], Haseltine and Wong-Staal [11], and Kirschner, Webb, and Cloyd [17].…”