Natural killer cells target HCV core proteins during the innate immune response in HCV transgenic mice
Natural killer cells target HCV core proteins during the innate immune response in HCV transgenic mice
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DOI：
10.1002/jmv.21859
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发表时间：
2010-09
影响因子：
12.7
通讯作者：
Kenichi Satoh;Hiroki Takahashi;C. Matsuda;Toshiyuki Tanaka;M. Miyasaka;M. Zeniya;M. Kohara
中科院分区：
文献类型：
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作者：
Kenichi Satoh;Hiroki Takahashi;C. Matsuda;Toshiyuki Tanaka;M. Miyasaka;M. Zeniya;M. Kohara
针对丙型肝炎病毒（HCV）的先天免疫反应机制尚未完全阐明，很大程度上是由于缺乏合适的模型。我们使用 HCV 转基因 (Tg) 小鼠（其表达受 Cre/loxP 转换表达系统调节的核心蛋白、E1、E2 和 NS2 蛋白）来检查对 HCV 结构蛋白的先天免疫反应。 HCV 转基因表达后 12 小时，Tg 小鼠肝脏中的 HCV 核心蛋白水平为 15-47 pg/mg。相比之下，在自然杀伤 (NK) 细胞耗尽的 Tg 小鼠中，我们观察到 HCV 核心蛋白水平要高得多 (1,597 pg/ml)。与未治疗的小鼠相比，在 0.5 至 1 天的 NK 细胞耗尽小鼠中，Cre 介导的 HCV-Tg 小鼠基因组 DNA 重组效率得到了强烈观察。这些数据表明，NK细胞参与HCV感染急性期先天免疫反应中核心表达肝细胞的消除。 J. Med。病毒。 82:1545–1553, 2010。© 2010 Wiley-Liss, Inc.
The mechanism of the innate immune response to hepatitis C virus (HCV) has not been fully elucidated, largely due to the lack of an appropriate model. We used HCV transgenic (Tg) mice, which express core, E1, E2, and NS2 proteins regulated by the Cre/loxP switching expression system, to examine the innate immune response to HCV structural proteins. Twelve hours after HCV transgene expression, HCV core protein levels in Tg mouse livers were 15–47 pg/mg. In contrast, in Tg mice with a depletion of natural killer (NK) cells, we observed much higher levels of HCV core proteins (1,597 pg/ml). Cre‐mediated genomic DNA recombination efficiency in the HCV‐Tg mice was strongly observed in NK cell‐depleted mice between 0.5 and 1 day as compared to non‐treated mice. These data indicated that NK cells participate in the elimination of core‐expressing hepatocytes in the innate immune responses during the acute phase of HCV infection. J. Med. Virol. 82:1545–1553, 2010. © 2010 Wiley‐Liss, Inc.