Effectiveness of a 'hunter' virus in controlling human immunodeficiency virus type 1 infection.
Engineered therapeutic viruses provide an alternative method for treating infectious diseases, and mathematical models can clarify the system's dynamics underlying this type of therapy. In particular, this study developed models to evaluate the potential to contain human immunodeficiency virus type 1 (HIV-1) infection using a genetically engineered 'hunter' virus that kills HIV-1-infected cells. First, we constructed a novel model for understanding the progression of HIV infection that predicted the loss of the immune system's CD4(+) T cells across time. Subsequently, it determined the effects of introducing hunter viruses in restoring cell population. The model implemented direct and indirect mechanisms by which HIV-1 may cause cell depletion and an immune response. Results suggest that the slow progression of HIV infection may result from a slowly decaying CTL immune response, leading to a limited but constant removal of uninfected CD4 resting cells through apoptosis - and from resting cell proliferation that reduces the rate of cell depletion over time. Importantly, results show that the hunter virus does restrain HIV infection and has the potential to allow major cell recovery to 'functional' levels. Further, the hunter virus persisted at a reduced HIV load and was effective either early or late in the infection. This study indicates that hunter viruses may halt the progression of the HIV infection by restoring and sustaining high CD4(+) T-cell levels.
García-Ramos
Gisela
G
Department of Biology, University of Kentucky, Lexington, KY 40506, USA. ggarc0@uky.edu
Castillo
Derik
D
Crowley
Philip H
PH
D001691:Biological Therapy / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D015658:HIV Infections / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D008962:Models, Theoretical; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology