带有 IFN 反应的 CD4 T 细胞中 HIV-1 复制的随机建模。

Stochastic Modelling of HIV-1 Replication in a CD4 T Cell with an IFN Response.

机构信息

Faculty of Science and Engineering, Swansea University, Bay Campus, Fabian Way SA1 8EN, UK.

Marchuk Institute of Numerical Mathematics of the RAS, 119333 Moscow, Russia.

出版信息

Viruses. 2023 Jan 20;15(2):296. doi: 10.3390/v15020296.

DOI:10.3390/v15020296

PMID:36851511

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9966781/

Abstract

A mathematical model of the human immunodeficiency virus Type 1 (HIV-1) life cycle in CD4 T cells was constructed and calibrated. It describes the activation of the intracellular Type I interferon (IFN-I) response and the IFN-induced suppression of viral replication. The model includes viral replication inhibition by interferon-induced antiviral factors and their inactivation by the viral proteins Vpu and Vif. Both deterministic and stochastic model formulations are presented. The stochastic model was used to predict efficiency of IFN-I-induced suppression of viral replication in different initial conditions for autocrine and paracrine effects. The probability of virion excretion for various MOIs and various amounts of IFN-I was evaluated and the statistical properties of the heterogeneity of HIV-1 and IFN-I production characterised.

摘要

构建并校准了一个描述人类免疫缺陷病毒 1 型（HIV-1）在 CD4 T 细胞中的生命周期的数学模型。该模型描述了细胞内 I 型干扰素（IFN-I）反应的激活以及 IFN 诱导的病毒复制抑制。该模型包括干扰素诱导的抗病毒因子的病毒复制抑制及其被病毒蛋白 Vpu 和 Vif 失活。本文呈现了确定性和随机模型的公式。使用随机模型来预测自分泌和旁分泌作用的不同初始条件下 IFN-I 诱导的病毒复制抑制效率。评估了不同 MOI 和不同 IFN-I 量的病毒粒子排泄概率，并对 HIV-1 和 IFN-I 产生的异质性的统计特性进行了特征描述。