Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi 710061, China.
Genome. 2020 Jun;63(6):307-317. doi: 10.1139/gen-2019-0161. Epub 2020 Apr 20.
The Himalayan marmot (), a natural host and transmitter of plague, is also susceptible to the hepadnavirus infection. To reveal the genetic basis of the hepadnavirus susceptibility and the immune response to plague, we systematically characterized the features of immune genes in Himalayan marmot with those of human and mouse. We found that the entire major histocompatibility complex region and the hepatitis B virus pathway genes of the Himalayan marmot were conserved with those of humans. A Trim (tripartite motif) gene cluster involved in immune response and antiviral activity displays dynamic evolution, which is reflected by the duplication of and the absence of and . Three key regions of Ntcp, which is critical for hepatitis B virus entry, had high identity among seven species of . Moreover, we observed a severe alveolar hemorrhage, inflammatory infiltrate in the infected lungs and livers from Himalayan marmots after infection of EV76, a live attenuated strain. Lots of immune genes were remarkably up-regulated, which several hub genes , , and are placed at the center of the gene network. These findings suggest that Himalayan marmot is a potential animal model for study on the hepadnavirus and plague infection.
喜马拉雅旱獭（）是鼠疫的天然宿主和传播者，也容易感染嗜肝 DNA 病毒。为了揭示嗜肝 DNA 病毒易感性和对鼠疫的免疫反应的遗传基础，我们系统地比较了喜马拉雅旱獭与人类和小鼠的免疫基因特征。我们发现，喜马拉雅旱獭的整个主要组织相容性复合体区域和乙型肝炎病毒途径基因与人类的基因保持保守。参与免疫反应和抗病毒活性的 Trim（三结构域）基因簇发生了动态进化，这反映在 和 的缺失和 的重复上。三个关键区域的 Ntcp，这对于乙型肝炎病毒进入至关重要，在七种 中具有高度的同一性。此外，我们观察到感染 EV76（一种活减毒 株）后，喜马拉雅旱獭的肺部和肝脏中出现严重的肺泡出血、炎症浸润。大量的免疫基因显著上调，其中几个枢纽基因 、 和 位于基因网络的中心。这些发现表明，喜马拉雅旱獭可能是研究嗜肝 DNA 病毒和鼠疫感染的潜在动物模型。
