Host factors influencing viral persistence
Host factors influencing viral persistence
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DOI：
10.1098/rstb.2000.0640
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发表时间：
2000-08-29
影响因子：
6.3
通讯作者：
Christensen, JP
中科院分区：
文献类型：
--
作者：
Thomsen, AR;Nansen, A;Christensen, JP
为了表征对非杀细胞病毒的抗病毒免疫应答，我们研究了一些基因敲除小鼠品系中淋巴细胞性脉络丛脑膜炎病毒感染的结果。使用了两种病毒株，它们在鼠宿主内传播和复制的能力明显不同。我们的研究结果表明，根据病毒株和宿主的免疫活性，可能会观察到非常不同的结果。因此，虽然在病毒控制的初始阶段，CD 4（+）细胞不是关键的，但感染性病毒在缺乏CD 4（+）细胞、B细胞或CD 40配体的小鼠中再次出现。病毒的重现与受损的长期CD 8（+）T细胞介导的免疫监视有关，病毒重现的时间与病毒的复制率呈负相关。我们的研究还表明，干扰素-γ是一种重要的细胞因子，根据病毒复制的速率，缺乏产生干扰素-γ能力的小鼠可能发展为严重的、大多致命的T细胞介导的消耗综合征或慢性感染，其特征在于抗病毒细胞毒性T淋巴细胞和感染性病毒的长期共存。数学模型表明，这些不同的结果可以用相对简单的数学术语来解释。这表明，建模可以作为一种手段来预测关键的主机和病毒参数。因此，将数学建模与精确、定量的葡萄分析相结合，看起来是解决免疫生物学中核心定量问题的一种有前途的方法。
With the aim of characterizing the antiviral immune response to a non-cytocidal virus, we studied the outcome of lymphocytic choriomeningitis virus infection in a number of gene knockout mouse strains. Two virus strains differing markedly in their capacity to spread and replicate inside the murine host were used. Our results reveal that very different outcomes may be observed depending on Virus strain and immunocompetence of the host. Thus while CD4(+) cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4(+) cells, B cells or CD40 ligand. Reappearance of virus is associated with impaired long-term CD8(+) T-cell mediated immune surveillance, and the time to virus resurgence is inversely correlated to the replication rate of the virus. Our studies also reveal that interferon-gamma is a central cytokine, and depending on the rate of virus replication, mice lacking the ability to product: interferon-gamma may develop either a severe, mostly fatal, T-cell mediated wasting syndrome or a chronic infection characterized by long-term coexistence of antiviral cytotoxic T lymphocytes and infectious virus. Mathematical modelling indicates that these different outcomes may be explained in relatively simple mathematical terms. This suggests that modelling may be used as a means to predict critical host and virus parameters. Therefore, combining mathematical modelling with precise, quantitative, in vine analyses looks to be a promising approach in addressing central quantitative issues in immunobiology.