Expression of the interleukin-18 gene from rhesus macaque by the simian immunodeficiency virus does not result in increased viral replication.
Expression of the interleukin-18 gene from rhesus macaque by the simian immunodeficiency virus does not result in increased viral replication.
复制标题
猿猴免疫缺陷病毒表达恒河猴的 IL-18 基因不会导致病毒复制增加。
DOI：
10.1089/107999001750133212
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Hodara,VL
中科院分区：
文献类型：
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作者：
Giavedoni,LD;Imhoof,JD;Velasquillo,MC;Parodi,LM;Hodara,VL
白细胞介素-18（IL-18），以前称为干扰素-γ（IFN-γ）-诱导因子（IGIF），是由活化的巨噬细胞表达的促炎细胞因子，其与IL-12协同作用作为促炎细胞因子。 IFN-γ产生和Th 1发育的重要放大因子。为了研究IL-18对慢病毒感染的影响，我们从恒河猴中克隆了IL-18基因，并构建了具有复制能力的 猴免疫缺陷病毒（SIV），其表达IL-18的前体pro-IL-18（SIVIL-18）或成熟形式（SIVmIL-18）。恒河猴IL-18的预测氨基酸序列 与人的同源性为96%，在193个残基中仅有8个残基不同。SIVIL-18和SIVmIL-18在CEM × 174细胞系中的复制速度比对照病毒慢， 在表达高水平感染性SIV的慢性感染细胞系的开发中。由SIVIL-18产生的细胞系将大量IL-18释放到上清液中， 而从SIVmIL-18获得的结果显示IL-18在细胞质中积累。同样，SIVIL-18和SIVmIL-18的复制速度也比未修饰的病毒慢， 载体在恒河猴外周血单个核细胞（PMBC）中表达，但只有SIVIL-18表达具有生物学活性的IL-18。这些实验表明，IL-18的前体形式对于免疫应答是必需的。 IL-18不能促进SIV在恒河猴PBMC中的复制。
Interleukin-18 (IL-18), previously known as interferon-γ (IFN-γ)-inducing factor (IGIF), is a proinflammatory cytokine expressed by activated macrophages that acts in synergy with IL-12 as an important amplifying factor for IFN-γ production and Th1 development. To study the effect of IL-18 on a lentiviral infection, we cloned the IL-18 gene from a rhesus macaque and constructed replication-competent simian immunodeficiency virus (SIV) that expressed either the precursor pro-IL-18 (SIVIL-18) or the mature form (SIVmIL-18) of IL-18. The predicted amino acid sequence for rhesus IL-18 had 96% homology with the human one, differing in only 8 of 193 residues. SIVIL-18and SIVmIL-18replicated more slowly than control viruses in the CEM × 174 cell line and resulted in the development of chronically infected cell lines that expressed high levels of infectious SIV. The cell line generated by SIVIL-18released large quantities of IL-18 into the supernatant, whereas the one obtained from SIVmIL-18showed the accumulation of IL-18 in the cytoplasm. Similarly, SIVIL-18and SIVmIL-18replicated more slowly than the unmodified viral vector in rhesus peripheral blood mononuclear cells (PMBC), but only SIVIL-18expressed biologically active IL-18. These experiments show that the precursor form of IL-18 is necessary for the efficient release of the cytokine and that IL-18 does not promote increased replication of SIV in rhesus PBMC.