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

• 来源期刊: 药学学报（英文版）
• 关键词: Filovirus Ebola Marburg Pseudovirus Entry inhibitor Mouse model
• 年，卷（期）: 2018,（2）
• 页码范围: 200-208
• 页数: 9页
• 语种: 英文

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 drugs.An HIV-based pseudovims 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 day 4 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.