Yang Zhangsheng, Du Jun, Chen Gang, Zhao Jie, Yang Xuanming, Su Lishan, Cheng Genhong, Tang Hong
Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China.
Virol Sin. 2014 Dec;29(6):393-402. doi: 10.1007/s12250-014-3530-y. Epub 2014 Dec 22.
It remains challenging to develop animal models of lung infection and severe pneumonia by severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome cornavirus (MERS-CoV) without high level of containment. This inevitably hinders understanding of virushost interaction and development of appropriate countermeasures. Here we report that intranasal inoculation of sublethal doses of murine coronavirus mouse hepatitis virus A-59 (MHV-A59), a hepatic and neuronal tropic coronavirus, can induce acute pneumonia and severe lung injuries in C57BL/6 mice. Inflammatory leukocyte infiltrations, hemorrhages and fibrosis of alveolar walls can be observed 2-11 days after MHV-A59 infection. This pathological manifestation is associated with dramatical elevation of tissue IP-10 and IFN-γ and moderate increase of TNF-α and IL-1β, but inability of anti-viral type I interferon response. These results suggest that intranasal infection of MHV-A59 would serve as a surrogate mouse model of acute respiratory distress syndrome by SARS-CoV and MERS-CoV infections.
在没有高级别隔离设施的情况下，利用严重急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒（MERS-CoV）开发肺部感染和严重肺炎的动物模型仍然具有挑战性。这不可避免地阻碍了对病毒与宿主相互作用的理解以及适当应对措施的开发。在此，我们报告鼻内接种亚致死剂量的鼠冠状病毒小鼠肝炎病毒A-59（MHV-A59），一种嗜肝和嗜神经的冠状病毒，可在C57BL/6小鼠中诱发急性肺炎和严重肺损伤。在MHV-A59感染后2至11天可观察到炎性白细胞浸润、出血和肺泡壁纤维化。这种病理表现与组织IP-10和IFN-γ的显著升高以及TNF-α和IL-1β的适度增加相关，但抗病毒I型干扰素反应缺失。这些结果表明，鼻内感染MHV-A59可作为SARS-CoV和MERS-CoV感染所致急性呼吸窘迫综合征的替代小鼠模型。
