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Visualization of Chikungunya Virus Infection in vitro and in vivo

33 Pages Posted: 11 Jun 2019

See all articles by Hong-Lei Zhang

Hong-Lei Zhang

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

Hao-Long Dong

Academy of Military Sciences - State Key Laboratory of Pathogen and Biosecurity

Lin-Lin Xu

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

Cheng-Lin Deng

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

Xiao-Feng Li

Academy of Military Sciences - State Key Laboratory of Pathogen and Biosecurity

Xiao-Dan Li

Hunan Normal University - School of Medicine

Han-Qing Ye

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

Zhi-Ming Yuan

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

Cheng-Feng Qin

Academy of Military Sciences - State Key Laboratory of Pathogen and Biosecurity

Bo Zhang

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

More...

Abstract

Background: Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has become a global public health concern. The lack of effective vaccines and antiviral agents are largely attributed to the elusive infection and dissemination dynamics in vivo.

Methods: In this study, we designed and developed a novel, replication-competent, CHIKV reporter virus (CHIKV-iRFP) encoding a near infrared fluorescent protein (iRFP) for in vivo imaging.

Findings: In vitro and in vivo characterization demonstrated that CHIKV-iRFP retained similar replication and virulence phenotype to the parental CHIKV. Neonatal BABL/c mice and IFNAR-/- A129 mice displayed highly susceptive to CHIKV-iRFP infection. Following intracranial (i.c.) inoculation, CHIKV-iRFP efficiently replicated and disseminated into whole body, resulting in rapid death in a age-dependent manner. Remarkably, upon i.c. inoculation, CHIKV-iRFP readily disseminated from footpad to the head and whole skeleton, with a specific tropism for bone marrow.

Interpretation: Taken together, this novel reporter virus provides a powerful tool to visualize CHIKV replication and to test the efficacy of vaccines and antiviral therapeutics in a noninvasive and real-time manner.

Funding: The National Key Research and Development Program of China (2018YFA0507201), the National Natural Science Foundation of China (No. 81572003).

Declaration of Interest: The authors declare no conflict of interest.

Ethical Approval: The experimental protocols were approved by the Animal Experiment Committee of Beijing Institute of Microbiology and Epidemiology, Beijing, China.

Keywords: Chikungunya Virus, iRFP, live imaging, mice

Suggested Citation

Zhang, Hong-Lei and Dong, Hao-Long and Xu, Lin-Lin and Deng, Cheng-Lin and Li, Xiao-Feng and Li, Xiao-Dan and Ye, Han-Qing and Yuan, Zhi-Ming and Qin, Cheng-Feng and Zhang, Bo, Visualization of Chikungunya Virus Infection in vitro and in vivo (May 24, 2019). Available at SSRN: https://ssrn.com/abstract=3393690 or http://dx.doi.org/10.2139/ssrn.3393690

Hong-Lei Zhang

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

China

Hao-Long Dong

Academy of Military Sciences - State Key Laboratory of Pathogen and Biosecurity

Beijing, 100071
China

Lin-Lin Xu

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

China

Cheng-Lin Deng

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

China

Xiao-Feng Li

Academy of Military Sciences - State Key Laboratory of Pathogen and Biosecurity

Beijing, 100071
China

Xiao-Dan Li

Hunan Normal University - School of Medicine

No. 36, Lushan Road
Yuelu District
Changsha, Hunan 410001
China

Han-Qing Ye

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

China

Zhi-Ming Yuan

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety

China

Cheng-Feng Qin

Academy of Military Sciences - State Key Laboratory of Pathogen and Biosecurity

Beijing, 100071
China

Bo Zhang (Contact Author)

Chinese Academy of Sciences (CAS) - Key Laboratory of Special Pathogens and Biosafety ( email )

China

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