Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Viruses, Cell Lines, Antibodies, and Animals
2.2. Treatment with Recombinant Murine IFN-λ
2.3. Isolation of Primary Astrocytes
2.4. Isolation of Primary Microglia
2.5. Construction and Rescue of Recombinant RABVs Expressing Murine IFN-λ
2.6. Fluorescence Morphologies of rRABV-Infected Cells
2.7. Virus Titration
2.8. ELISA
2.9. Quantitative Real-Time PCR (qRT-PCR)
2.10. Western Blot
2.11. Pathogenicity Studies
2.12. Luciferase Reporter Assay
2.13. Quantification of Cytokine Production
2.14. Transendothelial Permeability Assay
2.15. Immunohistochemistry (IHC) and Immunofluorescence
2.16. Measurement of BBB Permeability
2.17. Statistical Analysis
3. Results
3.1. IFN-λ Treatment Inhibits RABV Replication In Vitro
3.2. IFN-λ Attenuates the Pathogenicity of RABV In Vivo
3.3. IFN-λ Limits RABV Replication by Enhancing the Expression of ISGs
3.4. IFN-λ Avoids the Production of Excessive Inflammatory Cytokines
3.5. IFN-λ Restricts Infiltration of Inflammatory Cells into the CNS by Decreasing BBB Permeability
3.6. IFN-λ Maintains Endothelial Barrier Integrity
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Primers | Sequence (5′–3′) |
---|---|
IFNλ-BsiWI-F | TTGCGTACGATGCTCCTCCTGCTGTTG |
IFNλ-NheI-R | CTAGCTAGCTCAGACACACTGGTCTCC |
B2c-GL-F | CAGGGGGGAATGTGTCAGTC |
B2c-GL-R | GCCTCTGACTCAATTGGATC |
Primers | Sequence (5′–3′) |
---|---|
N mRNA-F | GATCGTGGAACACCATACCC |
N mRNA-R | TTCATAAGCGGTGACGACTG |
vRNA-F | CTCCACAACGAGATGCTCAA |
vRNA-R | CATCCAACGGGAACAAGACT |
IFN-a4-F | CCCACAGCCCAGAGAGTGACC |
IFN-a4-R | GGCCCTCTTGTTCCCGAGGT |
IFN-a5-F | CCTCAGGAACAAGAGAGCCTTA |
IFN-a5-R | TCCTGTGGGAATCCAAAGTC |
IFN-β-F | AGATGTCCTCAACTGCTCTC |
IFN-β-R | AGATTCACTACCAGTCCCAG |
IFIT2-F | TGGGGAAACTATGCTTGGGT |
IFIT2-R | CCTCACAGTCAAGAGCAGGA |
IIGP1-F | AATACCTGCCTCACGCTCAT |
IIGP1-R | GCTACTCTGTGGGTTCTGGC |
STAT1-F | CAGGTGTTGTCAGATCGAACCTTCC |
STAT1-R | TTCAGCTCTTGCAATTTCACCAACA |
NF-κB (p65)-F | CATTTCCGCCTCTGGCGAATG |
NF-κB (p65)-R | CGTTGCTTCGGCTGTTCGATG |
TNF-α-F | TCACTGGAGCCTCGAATGTC |
TNF-α-R | GTGAGGAAGGCTGTGCATTG |
ZO-1-F | GTCCCTCCTCTGATACCTTCCTC |
ZO-1-R | CTGGCAGTGTCATTCACATCTTTCT |
Occludin-F | TACAGACCCAAGAGCAGCA |
Occludin-R | AGCCGTACATAGATCCAGAA |
β-actin-F | CACTGCCGCATCCTCTTCCTCCC |
β-actin-R | CAATAGTGATGACCTGGCCGT |
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Li, Y.; Zhao, L.; Luo, Z.; Zhang, Y.; Lv, L.; Zhao, J.; Sui, B.; Huang, F.; Cui, M.; Fu, Z.F.; et al. Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation. Viruses 2020, 12, 405. https://doi.org/10.3390/v12040405
Li Y, Zhao L, Luo Z, Zhang Y, Lv L, Zhao J, Sui B, Huang F, Cui M, Fu ZF, et al. Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation. Viruses. 2020; 12(4):405. https://doi.org/10.3390/v12040405
Chicago/Turabian StyleLi, Yingying, Ling Zhao, Zhaochen Luo, Yachun Zhang, Lei Lv, Jianqing Zhao, Baokun Sui, Fei Huang, Min Cui, Zhen F. Fu, and et al. 2020. "Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation" Viruses 12, no. 4: 405. https://doi.org/10.3390/v12040405