Mechanistic basis of post-treatment control of SIV after anti-?4?7 antibody therapy [electronic resource]

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Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 610.28 Auxiliary techniques and procedures; apparatus, equipment, materials

Thông tin xuất bản: Bethesda, Md. : Oak Ridge, Tenn. : National Institutes of Health (U.S.) ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2021

Mô tả vật lý: Size: Article No. e1009031 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 259677

 Treating macaques with an anti-?4?7 antibody under the umbrella of combination antiretroviral therapy (cART) during early SIV infection can lead to viral remission, with viral loads maintained at <
  50 SIV RNA copies/ml after removal of all treatment in a subset of animals. Depletion of CD8+ lymphocytes in controllers resulted in transient recrudescence of viremia, suggesting that the combination of cART and anti-?4?7 antibody treatment led to a state where ongoing immune responses kept the virus undetectable in the absence of treatment. A previous mathematical model of HIV infection and cART incorporates immune effector cell responses and exhibits the property of two different viral load set-points. While the lower set-point could correspond to the attainment of long-term viral remission, attaining the higher set-point may be the result of viral rebound. Here we expand that model to include possible mechanisms of action of an anti-?4?7 antibody operating in these treated animals. We show that the model can fit the longitudinal viral load data from both IgG control and anti-?4?7 antibody treated macaques, suggesting explanations for the viral control associated with cART and an anti-?4?7 antibody treatment. This effective perturbation to the virus-host interaction can also explain observations in other nonhuman primate experiments in which cART and immunotherapy have led to post-treatment control or resetting of the viral load set-point. Interestingly, because the viral kinetics in the various treated animals differed?some animals exhibited large fluctuations in viral load after cART cessation?the model suggests that anti-?4?7 treatment could act by different primary mechanisms in different animals and still lead to post-treatment viral control. This outcome is nonetheless in accordance with a model with two stable viral load set-points, in which therapy can perturb the system from one set-point to a lower one through different biological mechanisms.
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