Simian virus 5 is a poor inducer of chemokine secretion from human lung epithelial cells: identification of viral mutants that activate interleukin-8 secretion by distinct mechanisms.
Simian virus 5 is a poor inducer of chemokine secretion from human lung epithelial cells: identification of viral mutants that activate interleukin-8 secretion by distinct mechanisms.
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猿猴病毒 5 是人肺上皮细胞趋化因子分泌的不良诱导剂：鉴定通过不同机制激活白细胞介素 8 分泌的病毒突变体。
DOI：
10.1128/jvi.77.12.7124-7130.2003
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发表时间：
2003
影响因子：
5.4
通讯作者：
Parks,GriffithD
中科院分区：
文献类型：
--
作者：
Young,VirginiaA;Parks,GriffithD
我们比较了感染猿病毒 5 (SV5) 和副粘病毒风疹病毒属其他成员的人肺 A549 细胞的趋化因子分泌。感染人副流感病毒 2 型 (HPIV-2) 的 A549 细胞分泌高水平的趋化因子白介素 8 (IL-8) 和巨噬细胞趋化蛋白 1 (MCP-1)，但感染野生型 (WT) SV5 的细胞则不分泌高水平的趋化因子白细胞介素 8 (IL-8) 和巨噬细胞趋化蛋白 1 (MCP-1)。 SV5感染的细胞缺乏IL-8分泌并不是由于导致IL-8分泌的所有信号转导途径的整体阻断，因为SV5感染的A549细胞在用外源添加的肿瘤坏死因子α刺激或与HPIV-2共感染后分泌IL-8。先前描述的重组 SV5 在 P/V 基因共享区域 (rSV5-P/V-CPI−) 中含有取代，通过依赖于病毒基因表达的机制诱导 IL-8 分泌。相比之下，从持续感染的细胞（犬副流感病毒的维克森林株）中分离出的 SV5 变体通过一种基本上不受病毒基因表达抑制剂影响的机制诱导 IL-8 分泌。总之，这些数据表明，与其他密切相关的副粘病毒相比，SV5 是不寻常的，因为 SV5 是细胞因子 IL-8 和 MCP-1 的非常差的诱导剂。分离两个在防止趋化因子诱导方面存在缺陷的重组SV5突变体将允许鉴定WT SV5所利用的机制，以避免激活宿主细胞对感染的先天免疫反应。
We have compared chemokine secretion from human lung A549 cells infected with simian virus 5 (SV5) with other members of theRubulavirusgenus of paramyxoviruses. High levels of the chemokines interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) were secreted from A549 cells infected withHuman parainfluenza virus type 2(HPIV-2) but not from cells infected with wild-type (WT) SV5. The lack of IL-8 secretion from SV5-infected cells was not due to a global block in all signal transduction pathways leading to IL-8 secretion, since SV5-infected A549 cells secreted IL-8 after stimulation with exogenously added tumor necrosis factor alpha or by coinfection with HPIV-2. A previously described, recombinant SV5 containing substitutions in the shared region of the P/V gene (rSV5-P/V-CPI−) induced IL-8 secretion by a mechanism that was dependent on viral gene expression. By contrast, an SV5 variant isolated from persistently infected cells (Wake Forest strain ofCanine parainfluenza virus) induced IL-8 secretion by a mechanism that was largely not affected by inhibitors of viral gene expression. Together, these data demonstrate that SV5 is unusual compared to other closely related paramyxoviruses, since SV5 is a very poor inducer of the cytokines IL-8 and MCP-1. The isolation of two recombinant SV5 mutants that are defective in preventing chemokine induction will allow an identification of mechanisms utilized by WT SV5 to avoid activation of host cell innate immune responses to infection.