Viral-host interaction in kidney reveals strategies to escape host immunity and persistently shed virus to the urine.
Viral-host interaction in kidney reveals strategies to escape host immunity and persistently shed virus to the urine.
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肾脏中病毒与宿主的相互作用揭示了逃避宿主免疫并持续将病毒排入尿液的策略
DOI：
10.18632/oncotarget.14227
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发表时间：
2017-01-31
期刊：
影响因子：
--
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Ou X;Mao S;Jiang Y;Zhang S;Ke C;Ma G;Cheng A;Wang M;Zhu D;Chen S;Jia R;Liu M;Sun K;Yang Q;Wu Y;Chen X
甲型肝炎病毒是导致人类肝病的五种嗜肝病毒之一。在由鸭甲型肝炎病毒(DHAV)引起的鸭子中也发现了类似的肝病。值得注意的是，在尿液中可以检测到许多类型的嗜肝病毒。然而，这些病毒是如何进入尿液的，在很大程度上还没有被探索。为了阐明可能的机制，我们使用禽嗜肝病毒研究了复制策略和肾脏的免疫反应，直到感染后280天。免疫组织化学和定量聚合酶链式反应检测病毒在肾脏中的分布和复制。采用CD_4~+、CD_8~+T细胞、病毒和qPCR双重染色检测T细胞免疫应答和细胞因子的表达水平。常规HE染色进行组织病理学检查。在本研究中，病毒持续存在于散在的肾小管上。肾脏没有招募到CD4+或CD8+T细胞，只是伴随着一过性的细胞因子风暴。总之，这种极其分散的感染是逃避宿主免疫的病毒策略，可能会持续将病毒排放到尿液中。Th或TC细胞应答的缺失和短暂的细胞因子风暴确实为他们的持续生存提供了有利的肾脏环境。
Hepatitis A virus is one of five types of hepatotropic viruses that cause human liver disease. A similar liver disease is also identified in ducks caused by Duck Hepatitis A virus (DHAV). Notably, many types of hepatotropic viruses can be detected in urine. However, how those viruses enter into the urine is largely unexplored. To elucidate the potential mechanism, we used the avian hepatotropic virus to investigate replication strategies and immune responses in kidney until 280 days after infection. Immunohistochemistry and qPCR were used to detect viral distribution and copies in the kidney. Double staining of CD4+ or CD8+ T cells and virus and qPCR were used to investigate T cell immune responses and expression levels of cytokines. Histopathology was detected by standard HE staining. In this study, viruses were persistently located at scattered renal tubules. No CD4+ or CD8+ T cells were recruited to the kidney, which was only accompanied by transient cytokine storms. In conclusion, the extremely scattered infection was the viral strategy to escape host immunity and may persistently shed virus into urine. The deletion of Th or Tc cell responses and transient cytokine storms indeed provide an advantageous renal environment for their persistent survival.