Bioluminescent Imaging of Vaccinia Virus Infection in Immunocompetent and Immunodeficient Rats As a Model for Human Smallpox

Overview

Journal Sci Rep

Specialty Science

Date 2015 Aug 4

PMID 26235050

Citations 11

Authors

Qiang Liu

Changfa Fan

Shuya Zhou

Yanan Guo

Qin Zuo

Jian Ma

Susu Liu

Xi Wu

Zexu Peng

Tao Fan

Chaoshe Guo

Yuelei Shen

Weijin Huang

Baowen Li

Zhengming He

Youchun Wang

Affiliations

Soon will be listed here.

Abstract

Due to the increasing concern of using smallpox virus as biological weapons for terrorist attack, there is renewed interest in studying the pathogenesis of human smallpox and development of new therapies. Animal models are highly demanded for efficacy and safety examination of new vaccines and therapeutic drugs. Here, we demonstrated that both wild type and immunodeficient rats infected with an engineered vaccinia virus carrying Firefly luciferase reporter gene (rTV-Fluc) could recapitulate infectious and clinical features of human smallpox. Vaccinia viral infection in wild type Sprague-Dawley (SD) rats displayed a diffusible pattern in various organs, including liver, head and limbs. The intensity of bioluminescence generated from rTV-Fluc correlated well with viral loads in tissues. Moreover, neutralizing antibodies had a protective effect against virus reinfection. The recombination activating gene 2 (Rag2) knockout rats generated by transcription activator-like effector nucleases (TALENs) technology were further used to examine the infectivity of the rTV-Fluc in immunodeficient populations. Here we demonstrated that Rag2-/- rats were more susceptible to rTV-Fluc than SD rats with a slower virus clearance rate. Therefore, the rTV-Fluc/SD rats and rTV-Fluc/Rag2-/- rats are suitable visualization models, which recapitulate wild type or immunodeficient populations respectively, for testing human smallpox vaccine and antiviral drugs.

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