Ou Xumin, Mao Sai, Jiang Yifan, Zhang Shengyong, Ke Chen, Ma Guangpeng, Cheng Anchun, Wang Mingshu, Zhu Dekang, Chen Shun, Jia Renyong, Liu Mafeng, Sun Kunfeng, Yang Qiao, Wu Ying, Chen Xiaoyue
Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan, People's Republic of China.
Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan, People's Republic of China.
Oncotarget. 2017 Jan 31;8(5):7336-7349. doi: 10.18632/oncotarget.14227.
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.
甲型肝炎病毒是导致人类肝脏疾病的五种嗜肝病毒之一。在鸭中也发现了由鸭甲型肝炎病毒（DHAV）引起的类似肝脏疾病。值得注意的是，在尿液中可以检测到多种嗜肝病毒。然而，这些病毒如何进入尿液在很大程度上尚未得到探索。为了阐明潜在机制，我们使用禽嗜肝病毒研究感染后280天内肾脏中的复制策略和免疫反应。采用免疫组织化学和qPCR检测病毒在肾脏中的分布和拷贝数。使用CD4+或CD8+ T细胞与病毒的双重染色以及qPCR来研究T细胞免疫反应和细胞因子的表达水平。通过标准HE染色检测组织病理学。在本研究中，病毒持续位于散在的肾小管处。没有CD4+或CD8+ T细胞被募集到肾脏，仅伴随着短暂的细胞因子风暴。总之，极其分散的感染是病毒逃避宿主免疫的策略，并且可能持续向尿液中排出病毒。Th或Tc细胞反应的缺失以及短暂的细胞因子风暴确实为它们的持续存活提供了有利的肾脏环境。
