Matrine exhibits antiviral activity in a PRRSV/PCV2 co-infected mouse model
Matrine exhibits antiviral activity in a PRRSV/PCV2 co-infected mouse model
复制标题
苦参碱在 PRRSV/PCV2 共感染小鼠模型中表现出抗病毒活性
DOI：
10.1016/j.phymed.2020.153289
复制
发表时间：
2020-10-01
期刊：
影响因子：
7.9
通讯作者：
Li, Hongquan
中科院分区：
文献类型：
--
作者：
Sun, Na;Zhang, Hua;Li, Hongquan
背景：猪繁殖与呼吸综合征病毒（PRRSV）和猪圆环病毒2型（PCV 2）混合感染在养猪业中十分普遍，在世界范围内造成了巨大的经济损失。虽然疫苗接种是预防病毒性疾病的有效手段，但由于PRRSV和PCV 2引起的免疫抑制，导致疫苗接种失败。目的：本实验室前期研究结果表明苦参碱具有抗PRRSV/PCV 2混合感染的体外活性。本研究旨在建立猪繁殖与呼吸综合征病毒（PRRSV）/猪圆环病毒2型（PCV 2）共感染KM小鼠模型，并评价苦参碱对PRRSV/PCV 2共感染KM小鼠的抗病毒作用。正常对照组、PRRSV/PCV 2共感染组（PRRSV/PCV 2组），利巴韦林处理阳性对照（利巴韦林对照）和苦参碱治疗组方法：除正常对照组外，其余5组小鼠均接种PRRSV，2 h后接种PCV 2。结果：PCR检测结果显示，在心、肝、脾、肺、肾、胸腺和腹股沟淋巴结等组织中均检测到PRRSV N和PCV 2 CAP基因。PCV 2在肝脏中的病毒载量最高，其次是胸腺和脾脏。qPCR分析表明，虽然在大部分组织中检测到了PRRSV，但病毒复制量并未明显增加。与PCV 2单独感染相比，PRRSV感染显著增加了PCV 2的复制，加重了PCV 2诱导的间质性肺炎。qPCR分析表明，40 mg/kg苦参碱可显著减弱肝脏中PCV 2的复制，并减轻病毒诱导的间质性肺炎，表明苦参碱可直接抑制病毒复制。此外，苦参碱处理增强腹腔巨噬细胞吞噬功能在13和16 dpi，和40 mg/kg的苦参碱增加淋巴细胞的增殖活性。结论：苦参碱对PRRSV/PCV 2共感染小鼠具有抗病毒作用，其作用机制可能与抑制病毒复制和调节免疫功能有关。这些数据为控制PRRSV和PCV 2感染提供了新的见解，并支持进一步研究开发苦参碱作为一种新的可能的兽药。
Background: PRRSV and PCV2 co-infection is very common in swine industry which results in huge economic losses worldwide. Although vaccination is used to prevent viral diseases, immunosuppression induced by PRRSV and PCV2 leads to vaccine failure.Purpose: Our previous results have demonstrated that Matrine possess antiviral activities against PRRSV/PCV2 co-infection in vitro. This study aims to establish a PRRSV/PCV2 co-infected KM mouse model and evaluate the antiviral activities of Matrine against PRRSV/PCV2 co-infection.Study design: A total of 144 KM mice were randomly divided into six groups with 24 mice in each group, named as: normal control, PRRSV/PCV2 co-infected group (PRRSV/PCV2 group), Ribavirin treatment positive control (Ribavirin control) and Matrine treatment groups (Matrine 40 mg/kg, Matrine 20 mg/kg and Matrine 10 mg/kg).Methods: Except normal control group, all mice in other five groups were inoculated with PRRSV, followed by PCV2 at 2 h later. At 7 days post-infection (dpi), mice in the treatment groups were intraperitoneally administered with various doses of Matrine and Ribavirin, twice a day for 5 consecutive days.Results: PRRSV N and PCV2 CAP genes were detected by PCR in multiple tissues including heart, liver, spleen, lungs, kidneys, thymus and inguinal lymph nodes. The viral load of PCV2 was the highest in liver followed by thymus and spleen. Although PRRSV were detected in most of tissues, but the replication of PRRSV was not significantly increased, as shown by qPCR analysis. Comparing with PCV2 infection alone, PRRSV infection significantly elevated PCV2 replication and exacerbated PCV2 induced interstitial pneumonia. qPCR analysis demonstrated 40 mg/kg Matrine significantly attenuated PCV2 replication in liver and alleviated virus induced interstitial pneumonia, suggesting Matrine could directly inhibit virus replication. In addition, Matrine treatment enhanced peritoneal macrophages phagocytosis at 13 and 16 dpi, and 40 mg/kg of Matrine increased the proliferation activity of lymphocytes. Body weight gain was continuously promoted by administrating Matrine at 10 mg/kg.Conclusion: Matrine possessed antiviral activities via inhibiting virus replication and regulating immune functions in mice co-infected by PRRSV/PCV2. These data provide new insight into controlling PRRSV and PCV2 infection and support further research for developing Matrine as a new possible veterinary medicine.