Establishment of pseudovirus infection mouse models for pharmacodynamics evaluation of filovirus entry inhibitors.
10.1016/j.apsb.2017.08.003
- Author:
Qing CHEN
1
;
Ke TANG
1
;
Xiaoyu ZHANG
1
;
Panpan CHEN
1
;
Ying GUO
1
Author Information
1. 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, Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
3D, 3-dimensional;
BDBV, Bundibugyo virus;
BSL, Biosafety Level;
CLO, clomiphene;
DLIT, Diffuse Luminescence Imaging Tomography;
EBOV, Ebola virus;
Ebola;
Entry inhibitor;
Filovirus;
GP, glycoprotein;
IC50, the 50% inhibitory concentration;
LLOV, Lloviu virus;
MARV, Marburg virus;
Marburg;
Mouse model;
Pseudovirus;
RAVV, Ravn virus;
RESTV, Reston virus;
ROI, region of interest;
SD, standard deviation;
SEM, standard error of the mean;
SUDV, Sudan virus;
TAFV, Taï forest virus;
TORE, toremiphene;
VSV-G, vesicular stomatitis virus glycoprotein;
d.p.i., day post-infection;
h.p.i., hour post-infection;
i.p., intraperitoneally;
lg, logarithm
- From:
Acta Pharmaceutica Sinica B
2018;8(2):200-208
- CountryChina
- Language:English
-
Abstract:
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 pseudovirus cell infection assay is widely used for viral entry studies in BSL-2 conditions. Here, we successfully constructed nine pseudo-filovirus models covering all filovirus genera and three 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 . The pseudo-filovirus-infection mouse models can be used for activity evaluation of anti-filovirus drugs. This sequential and evaluation system of filovirus entry inhibitors provides a secure and efficient platform for screening and assessing anti-filovirus agents in BSL-2 facilities.
