Establishment of pseudovirus infection mouse models for in vivo pharmacodynamics evaluation of filovirus entry inhibitors

作     者：Qing Chen Ke Tang Xiaoyu Zhang Panpan Chen Ying Guo 

作者机构：State Key Laboratory of Bioactive Substances and Function of Natural Medicines Department of Pharmacology Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2018年第8卷第2期

页      面：200-208页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China (81202568, 81473256, and 81273561) the National Science and Technology Major Project (2015ZX09102-023-004) the CAMS Innovation Fund for Medical Sciences (2016-I2M-1–014) the Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study (BZ0150) 

主　　题：Filovirus Ebola Marburg Pseudovirus Entry inhibitor Mouse model 

摘      要：Filoviruses cause severe and fatal viral hemorrhagic fever in humans. Filovirus research has been extensive since the 2014 Ebola outbreak. Due to their high pathogenicity and mortality, live filoviruses require Biosafety Level-4(BSL-4) facilities, which have restricted the development of anti-filovirus vaccines and *** HIV-based pseudovirus cell infection assay is widely used for viral entry studies in BSL-2 conditions. Here,we successfully constructed nine in vitro pseudo-filovirus models covering all filovirus genera and three in vivo pseudo-filovirus-infection mouse models using Ebola virus, Marburg virus, and Lloviu virus as representative viruses. The pseudo-filovirus-infected mice showed visualizing bioluminescence in a dose-dependent manner. A bioluminescence peak in mice was reached on day 5 post-infection for Ebola virus and Marburg virus and on day4 post-infection for Lloviu virus. Two known filovirus entry inhibitors, clomiphene and toremiphene, were used to validate the model. Collectively, our study shows that all genera of filoviruses can be well-pseudotyped and are infectious in vitro. The pseudo-filovirus-infection mouse models can be used for in vivo activity evaluation of anti-filovirus drugs. This sequential in vitro and in vivo evaluation system of filovirus entry inhibitors provides a secure and efficient platform for screening and assessing anti-filovirus agents in BSL-2 facilities.