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本研究探讨不同剂量DPP4转导小鼠后对中东呼吸综合征冠状病毒(Middle East respiratory syndrome coronavirus,MERS-CoV)感染建模及其生物特性的影响。首先将表达MERS-CoV受体DPP4的重组腺病毒以高剂量(2.5×108 PFU/只)、低剂量(0.5×108 PFU/只)分别转导转导BALB/c小鼠,继而滴鼻接种MERS-CoV,建立MERS-CoV感染小鼠模型。对成功构建的小鼠感染模型分别进行体征、病毒复制、免疫病理及抗体应答的比较分析。结果表明:两种剂量DPP4转导后MERS-CoV感染小鼠,均可引起典型肺炎表征,在小鼠肺部能检测到病毒复制及免疫病理,但高剂量DPP4转导组小鼠肺炎体征与肺病理损伤更明显,病毒复制水平亦高于低剂量DPP4转导组。小鼠感染建模后2w后可检测到结构蛋白特异抗体与中和抗体,高剂量DPP4转导组抗体应答亦明显高于低剂量转导组。本研究以两种剂量DPP4转导小鼠,均成功建立了MERS-CoV感染的小鼠模型,受体DPP4转导水平可影响MERS-CoV感染小鼠体征、病毒复制及抗体应答。
This study was designed to investigate the effects of different doses of DPP4-transduced mice on the modeling of MERS-CoV infections and their biological characteristics. First, the recombinant adenovirus expressing the MERS-CoV receptor DPP4 was transduced into BALB / c mice at high dose (2.5 × 108 PFU / mouse) and low dose (0.5 × 108 PFU / mouse), respectively, followed by intranasal inoculation MERS-CoV, a mouse model of MERS-CoV infection was established. Mouse model of infection was successfully constructed for signs, virus replication, immunopathology and antibody response to the comparative analysis. The results showed that mice infected with MERS-CoV after two doses of DPP4 transduced all could induce typical pneumonia, and virus replication and immunopathology could be detected in the lungs of mice. However, the signs of pneumonia in mice treated with high dose DPP4 transduction Pulmonary pathological damage is more obvious, the level of virus replication is also higher than low-dose DPP4 transduction group. Structural protein specific antibodies and neutralizing antibodies were detected 2 weeks after infection in mice. The antibody response of DPP4 transfection group was also significantly higher than that of low-dose transfection group. In this study, mice were transduced with DPP4 at two different dosages. Mouse models of MERS-CoV infection were successfully established. DPP4 transduction level could affect the signs of MERS-CoV infected mice and the antibody response.