Effectiveness of a 'hunter' virus in controlling human immunodeficiency virus type 1 infection

被引:1
作者
Garcia-Ramos, Gisela [1 ]
Castillo, Derik [1 ]
Crowley, Philip H. [1 ]
机构
[1] Univ Kentucky, Dept Biol, Lexington, KY 40506 USA
基金
美国国家科学基金会;
关键词
T-CELL DEPLETION; ANTIRETROVIRAL THERAPY; POPULATION BIOLOGY; IMMUNE-RESPONSES; HIV-1; INFECTION; LIFE-SPAN; DYNAMICS; CD4(+); LYMPHOCYTES; MODEL;
D O I
10.1099/vir.0.023028-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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
引用
收藏
页码:2513 / 2523
页数:11
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