. doi: 10.1016/j.virs.2023.04.007
Citation: Xiaojing Lin, Murong Zhu, Xiujuan Zhao, Longlong Si, Meiyue Dong, Varada Anirudhan, Qinghua Cui, Lijun Rong, Ruikun Du. Optimization and applications of an in vivo bioluminescence imaging model of influenza A virus infections .VIROLOGICA SINICA, 2023, 38(4) : 631-634.  http://dx.doi.org/10.1016/j.virs.2023.04.007

一种流感小鼠活体成像模型的优化和应用

  • 流感病毒分节段基因组对于外源基因插入修饰的容纳能力较低,导致流感报告病毒构建难度增大,限制了流感小鼠活体成像模型的建立和应用。前期,我们通过开发一种“平衡补偿”策略,成功构建了携带萤火虫荧光素酶基因(Fluc)的重组流感报告病毒,进而建立了稳健的流感小鼠活体成像模型。本研究通过对该模型进行评价和优化,将其应用于探究流感病毒学基础及应用相关的重要科学问题。

Optimization and applications of an in vivo bioluminescence imaging model of influenza A virus infections

  • Highlights
    1. The in vivo BLI model of IAV infections can simplify the determination of viral load in living animals;
    2. The in vivo BLI model of IAV infections allow longitudinal measurements of virus infection/spread in living animals;
    3. The in vivo BLI model of IAV infections improved the throughput of animal models;
    4. The advanced BLI models can facilitate studies in both basic and applied virology.

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    1. Aso, K., Tsuruhara, A., Takagaki, K., Oki, K., Ota, M., Nose, Y., Tanemura, H., Urushihata, N., Sasanuma, J., Sano, M., Hirano, A., Aso, R., McGhee, J.R., Fujihashi, K., 2016. Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice. PLoS One 11, e0148185.

    2. Bates, J.T., Honko, A.N., Graff, A.H., Kock, N.D., Mizel, S.B., 2008. Mucosal adjuvant activity of flagellin in aged mice. Mech Ageing Dev 129, 271-281.

    3. Belser, J.A., Gustin, K.M., Pearce, M.B., Maines, T.R., Zeng, H., Pappas, C., Sun, X., Carney, P.J., Villanueva, J.M., Stevens, J., Katz, J.M., Tumpey, T.M., 2013. Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice. Nature 501, 556-559.

    4. Chen, W.H., Kozlovsky, B.F., Effros, R.B., Grubeck-Loebenstein, B., Edelman, R., Sztein, M.B., 2009. Vaccination in the elderly:an immunological perspective. Trends Immunol 30, 351-359.

    5. Du, R., Cheng, H., Cui, Q., Peet, N.P., Gaisina, I.N., Rong, L., 2021a. Identification of a novel inhibitor targeting influenza A virus group 2 hemagglutinins. Antiviral Res 186, 105013.

    6. Du, R., Cui, Q., Rong, L., 2021b. Flu Universal Vaccines:New Tricks on an Old Virus. Virol Sin 36, 13-24.

    7. Govorkova, E.A., Leneva, I.A., Goloubeva, O.G., Bush, K., Webster, R.G., 2001. Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. Antimicrob Agents Chemother 45, 2723-2732.

    8. Harris, R., Yang, J., Pagan, K., Cho, S.J., Stout-Delgado, H., 2021. Antiviral Gene Expression in Young and Aged Murine Lung during H1N1 and H3N2. Int J Mol Sci 22.

    9. Iuliano, A.D., Roguski, K.M., Chang, H.H., Muscatello, D.J., Palekar, R., Tempia, S., Cohen, C., Gran, J.M., Schanzer, D., Cowling, B.J., Wu, P., Kyncl, J., Ang, L.W., Park, M., Redlberger-Fritz, M., Yu, H., Espenhain, L., Krishnan, A., Emukule, G., van Asten, L., Pereira da Silva, S., Aungkulanon, S., Buchholz, U., Widdowson, M.A., Bresee, J.S., 2018. Estimates of global seasonal influenza-associated respiratory mortality:a modelling study. Lancet 391, 1285-1300.

    10. Kandasamy, M., Furlong, K., Perez, J.T., Manicassamy, S., Manicassamy, B., 2020. Suppression of Cytotoxic T Cell Functions and Decreased Levels of Tissue-Resident Memory T Cells during H5N1 Infection. J Virol 94.

    11. Lu, J., Duan, X., Zhao, W., Wang, J., Wang, H., Zhou, K., Fang, M., 2018. Aged Mice are More Resistant to Influenza Virus Infection due to Reduced Inflammation and Lung Pathology. Aging Dis 9, 358-373.

    12. Mehle, A., 2015. Fiat Luc:Bioluminescence Imaging Reveals In Vivo Viral Replication Dynamics. PLoS Pathog 11, e1005081.

    13. Si, L., Shen, Q., Li, J., Chen, L., Shen, J., Xiao, X., Bai, H., Feng, T., Ye, A.Y., Li, L., Zhang, C., Li, Z., Wang, P., Oh, C.Y., Nurani, A., Niu, S., Zhang, C., Wei, X., Yuan, W., Liao, H., Huang, X., Wang, N., Tian, W.X., Tian, H., Li, L., Liu, X., Plebani, R., 2022. Generation of a live attenuated influenza A vaccine by proteolysis targeting. Nat Biotechnol 40, 1370-1377.

    14. Talbot, H.K., 2017. Influenza in Older Adults. Infect Dis Clin North Am 31, 757-766.

    15. Wen, X., Zhang, L., Liu, Q., Xiao, X., Huang, W., Wang, Y., 2022. Screening and identification of HTNV(pv) entry inhibitors with high-throughput pseudovirus-based chemiluminescence. Virol Sin 37, 531-537.

    16. Zhao, X., Lin, X., Li, P., Chen, Z., Zhang, C., Manicassamy, B., Rong, L., Cui, Q., Du, R., 2022. Expanding the tolerance of segmented Influenza A Virus genome using a balance compensation strategy. PLoS Pathog 18, e1010756.

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    Optimization and applications of an in vivo bioluminescence imaging model of influenza A virus infections

      Corresponding author: Qinghua Cui, cuiqinghua@sdutcm.edu.cn
      Corresponding author: Lijun Rong, lijun@uic.edu
      Corresponding author: Ruikun Du, ruikun@sdutcm.edu.cn
    • a. Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 50355, China;
    • b. CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China;
    • c. Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA;
    • d. Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, 266122, China

    Abstract: Highlights
    1. The in vivo BLI model of IAV infections can simplify the determination of viral load in living animals;
    2. The in vivo BLI model of IAV infections allow longitudinal measurements of virus infection/spread in living animals;
    3. The in vivo BLI model of IAV infections improved the throughput of animal models;
    4. The advanced BLI models can facilitate studies in both basic and applied virology.

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