Noninvasive bioluminescence imaging of dengue virus infection in the brain of A129 mice

Xiao Feng Li, Yong Qiang Deng, Hui Zhao, Qing Ye, Hong Jiang Wang, Shi Hua Li, Shun Ya Zhu, Pei-Yong Shi, E. De Qin, Bo Zhang, Cheng Feng Qin

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Dengue virus (DENV) infection is one of the most important public health threats globally; however, no vaccines or effective antivirals are currently available. The bioluminescence imaging technique has emerged as a powerful tool for studies on viral pathogenesis in vitro and in vivo. In this study, using a recombinant DENV that stably expressed Renilla luciferase (Rluc-DENV), we used bioluminescence for imaging of DENV infection in the brain of A129 mice that lacked type I interferon receptors. Upon intracranial inoculation with Rluc-DENV, A129 mice developed typical neurological symptoms and rapidly succumbed to viral infection. Real-time bioluminescence intensity analysis revealed the replication kinetics of Rluc-DENV in the brain of A129 mice. Linear regression analyses showed a good correlation between photon flux and viral titers (R 2 = 0.9923). Finally, the bioluminescence model was validated using a known mouse monoclonal antibody, 2A10G6, and the therapeutic effects of this neutralizing antibody were readily monitored by live imaging in the same animal. The noninvasive bioluminescence imaging of DENV infection as described here shows distinct advantages over traditional animal models and provides a powerful tool for potential antiviral or vaccine assays against DENV infection in vivo.

Original languageEnglish (US)
Pages (from-to)4589-4596
Number of pages8
JournalApplied Microbiology and Biotechnology
Volume97
Issue number10
DOIs
StatePublished - May 2013
Externally publishedYes

Fingerprint

Dengue Virus
Virus Diseases
Brain
Antiviral Agents
Vaccines
Renilla Luciferases
Interferon alpha-beta Receptor
Therapeutic Uses
Neutralizing Antibodies
Photons
Linear Models
Animal Models
Public Health
Monoclonal Antibodies
Regression Analysis

Keywords

  • 2A10G6
  • A129 mice
  • Bioluminescence imaging
  • Dengue virus

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

Cite this

Li, X. F., Deng, Y. Q., Zhao, H., Ye, Q., Wang, H. J., Li, S. H., ... Qin, C. F. (2013). Noninvasive bioluminescence imaging of dengue virus infection in the brain of A129 mice. Applied Microbiology and Biotechnology, 97(10), 4589-4596. https://doi.org/10.1007/s00253-013-4799-8

Noninvasive bioluminescence imaging of dengue virus infection in the brain of A129 mice. / Li, Xiao Feng; Deng, Yong Qiang; Zhao, Hui; Ye, Qing; Wang, Hong Jiang; Li, Shi Hua; Zhu, Shun Ya; Shi, Pei-Yong; Qin, E. De; Zhang, Bo; Qin, Cheng Feng.

In: Applied Microbiology and Biotechnology, Vol. 97, No. 10, 05.2013, p. 4589-4596.

Research output: Contribution to journalArticle

Li, XF, Deng, YQ, Zhao, H, Ye, Q, Wang, HJ, Li, SH, Zhu, SY, Shi, P-Y, Qin, ED, Zhang, B & Qin, CF 2013, 'Noninvasive bioluminescence imaging of dengue virus infection in the brain of A129 mice', Applied Microbiology and Biotechnology, vol. 97, no. 10, pp. 4589-4596. https://doi.org/10.1007/s00253-013-4799-8
Li, Xiao Feng ; Deng, Yong Qiang ; Zhao, Hui ; Ye, Qing ; Wang, Hong Jiang ; Li, Shi Hua ; Zhu, Shun Ya ; Shi, Pei-Yong ; Qin, E. De ; Zhang, Bo ; Qin, Cheng Feng. / Noninvasive bioluminescence imaging of dengue virus infection in the brain of A129 mice. In: Applied Microbiology and Biotechnology. 2013 ; Vol. 97, No. 10. pp. 4589-4596.
@article{3bdda674b62a40ae939802dbd9e9be8a,
title = "Noninvasive bioluminescence imaging of dengue virus infection in the brain of A129 mice",
abstract = "Dengue virus (DENV) infection is one of the most important public health threats globally; however, no vaccines or effective antivirals are currently available. The bioluminescence imaging technique has emerged as a powerful tool for studies on viral pathogenesis in vitro and in vivo. In this study, using a recombinant DENV that stably expressed Renilla luciferase (Rluc-DENV), we used bioluminescence for imaging of DENV infection in the brain of A129 mice that lacked type I interferon receptors. Upon intracranial inoculation with Rluc-DENV, A129 mice developed typical neurological symptoms and rapidly succumbed to viral infection. Real-time bioluminescence intensity analysis revealed the replication kinetics of Rluc-DENV in the brain of A129 mice. Linear regression analyses showed a good correlation between photon flux and viral titers (R 2 = 0.9923). Finally, the bioluminescence model was validated using a known mouse monoclonal antibody, 2A10G6, and the therapeutic effects of this neutralizing antibody were readily monitored by live imaging in the same animal. The noninvasive bioluminescence imaging of DENV infection as described here shows distinct advantages over traditional animal models and provides a powerful tool for potential antiviral or vaccine assays against DENV infection in vivo.",
keywords = "2A10G6, A129 mice, Bioluminescence imaging, Dengue virus",
author = "Li, {Xiao Feng} and Deng, {Yong Qiang} and Hui Zhao and Qing Ye and Wang, {Hong Jiang} and Li, {Shi Hua} and Zhu, {Shun Ya} and Pei-Yong Shi and Qin, {E. De} and Bo Zhang and Qin, {Cheng Feng}",
year = "2013",
month = "5",
doi = "10.1007/s00253-013-4799-8",
language = "English (US)",
volume = "97",
pages = "4589--4596",
journal = "Applied Microbiology and Biotechnology",
issn = "0175-7598",
publisher = "Springer Verlag",
number = "10",

}

TY - JOUR

T1 - Noninvasive bioluminescence imaging of dengue virus infection in the brain of A129 mice

AU - Li, Xiao Feng

AU - Deng, Yong Qiang

AU - Zhao, Hui

AU - Ye, Qing

AU - Wang, Hong Jiang

AU - Li, Shi Hua

AU - Zhu, Shun Ya

AU - Shi, Pei-Yong

AU - Qin, E. De

AU - Zhang, Bo

AU - Qin, Cheng Feng

PY - 2013/5

Y1 - 2013/5

N2 - Dengue virus (DENV) infection is one of the most important public health threats globally; however, no vaccines or effective antivirals are currently available. The bioluminescence imaging technique has emerged as a powerful tool for studies on viral pathogenesis in vitro and in vivo. In this study, using a recombinant DENV that stably expressed Renilla luciferase (Rluc-DENV), we used bioluminescence for imaging of DENV infection in the brain of A129 mice that lacked type I interferon receptors. Upon intracranial inoculation with Rluc-DENV, A129 mice developed typical neurological symptoms and rapidly succumbed to viral infection. Real-time bioluminescence intensity analysis revealed the replication kinetics of Rluc-DENV in the brain of A129 mice. Linear regression analyses showed a good correlation between photon flux and viral titers (R 2 = 0.9923). Finally, the bioluminescence model was validated using a known mouse monoclonal antibody, 2A10G6, and the therapeutic effects of this neutralizing antibody were readily monitored by live imaging in the same animal. The noninvasive bioluminescence imaging of DENV infection as described here shows distinct advantages over traditional animal models and provides a powerful tool for potential antiviral or vaccine assays against DENV infection in vivo.

AB - Dengue virus (DENV) infection is one of the most important public health threats globally; however, no vaccines or effective antivirals are currently available. The bioluminescence imaging technique has emerged as a powerful tool for studies on viral pathogenesis in vitro and in vivo. In this study, using a recombinant DENV that stably expressed Renilla luciferase (Rluc-DENV), we used bioluminescence for imaging of DENV infection in the brain of A129 mice that lacked type I interferon receptors. Upon intracranial inoculation with Rluc-DENV, A129 mice developed typical neurological symptoms and rapidly succumbed to viral infection. Real-time bioluminescence intensity analysis revealed the replication kinetics of Rluc-DENV in the brain of A129 mice. Linear regression analyses showed a good correlation between photon flux and viral titers (R 2 = 0.9923). Finally, the bioluminescence model was validated using a known mouse monoclonal antibody, 2A10G6, and the therapeutic effects of this neutralizing antibody were readily monitored by live imaging in the same animal. The noninvasive bioluminescence imaging of DENV infection as described here shows distinct advantages over traditional animal models and provides a powerful tool for potential antiviral or vaccine assays against DENV infection in vivo.

KW - 2A10G6

KW - A129 mice

KW - Bioluminescence imaging

KW - Dengue virus

UR - http://www.scopus.com/inward/record.url?scp=84877779274&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877779274&partnerID=8YFLogxK

U2 - 10.1007/s00253-013-4799-8

DO - 10.1007/s00253-013-4799-8

M3 - Article

C2 - 23467830

AN - SCOPUS:84877779274

VL - 97

SP - 4589

EP - 4596

JO - Applied Microbiology and Biotechnology

JF - Applied Microbiology and Biotechnology

SN - 0175-7598

IS - 10

ER -