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Article

The Establishment of a Noninvasive Bioluminescence-Specific Viral Encephalitis Model by Pseudorabies Virus-Infected NF-κBp-Luciferase Mice

by 1,2,†, 3,4,†, 5, 6,7, 8, 9,10, 11, 3,12,13,* and 3,4,*
1
Department of Optometry, Asia University, Taichung 40354, Taiwan
2
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40201, Taiwan
3
Department of Microbiology and Immunology, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
4
Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
5
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan
6
Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
7
Department of Pathology, Chung-Shan Medical University Hospital, Taichung 40201, Taiwan
8
Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
9
Department of Pharmacology, School of Medicine, China Medical University, Taichung 40201, Taiwan
10
Department of Photonics and Communication Engineering, Asia University, Taichung 40201, Taiwan
11
Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, Taichung 40201, Taiwan
12
Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
13
Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chung Shan, Medical University Hospital, Taichung 40201, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Kwonil Jung
Vet. Sci. 2022, 9(3), 113; https://doi.org/10.3390/vetsci9030113
Received: 19 January 2022 / Revised: 23 February 2022 / Accepted: 25 February 2022 / Published: 3 March 2022
Encephalitis is a rare brain inflammation that is most commonly caused by a viral infection. In this study, we first use an in vivo imaging system (IVIS) to determine whether NF-κBp-luciferase expression could be detected in the brain of pseudorabies virus (PRV)-infected NF-κBp-luciferase mice and to evaluate proinflammatory mediators in a well-described mouse model of PRV encephalitis. In in vitro studies, we used murine microglia (BV-2) cells to demonstrate the PRV-induced encephalitis model entailing the activation of microglia cells. The results indicate that PRV-induced neuroinflammation responses through the induction of IL-6, TNF-α, COX-2, and iNOS expression occurred via the regulation of NF-κB expression in BV-2 cells. In in vivo studies, compared with MOCK controls, the mice infected with neurovirulent PRV exhibited significantly elevated NF-κB transcription factor activity and luciferase protein expression only in the brain by IVIS. Mild focal necrosis was also observed in the brain. Further examination revealed biomarkers of inflammation, including inducible cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α and interleukin (IL)-6, both of which constituted proinflammatory cytokines. PRV infection stimulated inflammation and COX-2 and iNOS expression of IL-6 and TNF-α. The presented results herein suggest that PRV induces iNOS and COX-2 expression in the brain of NF-κBp–luciferase mice via NF-κB activation. In conclusion, we used NF-κBp-luciferase mice to establish a specific virus-induced encephalitis model via PRV intranasal infection. In the future, this in vivo model will provide potential targets for the development of new therapeutic strategies focusing on NF-κB inflammatory biomarkers and the development of drugs for viral inflammatory diseases. View Full-Text
Keywords: pseudorabies virus (PRV); nuclear factor-kappa B promoter (NF-κBp)-luciferase mice; proinflammatory mediators pseudorabies virus (PRV); nuclear factor-kappa B promoter (NF-κBp)-luciferase mice; proinflammatory mediators
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MDPI and ACS Style

Lin, H.-W.; Wang, M.; Tsai, P.-J.; Lee, Y.-J.; Hsieh, M.-C.; Lu, D.-Y.; Hsu, W.-L.; Jan, M.-S.; Chang, Y.-Y. The Establishment of a Noninvasive Bioluminescence-Specific Viral Encephalitis Model by Pseudorabies Virus-Infected NF-κBp-Luciferase Mice. Vet. Sci. 2022, 9, 113. https://doi.org/10.3390/vetsci9030113

AMA Style

Lin H-W, Wang M, Tsai P-J, Lee Y-J, Hsieh M-C, Lu D-Y, Hsu W-L, Jan M-S, Chang Y-Y. The Establishment of a Noninvasive Bioluminescence-Specific Viral Encephalitis Model by Pseudorabies Virus-Infected NF-κBp-Luciferase Mice. Veterinary Sciences. 2022; 9(3):113. https://doi.org/10.3390/vetsci9030113

Chicago/Turabian Style

Lin, Hui-Wen, Meilin Wang, Pei-Jane Tsai, Yi-Ju Lee, Ming-Chang Hsieh, Dah-Yuu Lu, Wei-Li Hsu, Ming-Shiou Jan, and Yuan-Yen Chang. 2022. "The Establishment of a Noninvasive Bioluminescence-Specific Viral Encephalitis Model by Pseudorabies Virus-Infected NF-κBp-Luciferase Mice" Veterinary Sciences 9, no. 3: 113. https://doi.org/10.3390/vetsci9030113

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