Citation: Weide Su, Jingjiang Qiu, Ying Mei, Xian-En Zhang, Yong He, Feng Li. A microfluidic cell chip for virus isolation via rapid screening for permissive cells .VIROLOGICA SINICA, 2022, 37(4) : 547-557.  http://dx.doi.org/10.1016/j.virs.2022.04.011

A microfluidic cell chip for virus isolation via rapid screening for permissive cells

  • Virus identification is a prerequisite not only for the early diagnosis of viral infectious diseases but also for the effective prevention of epidemics. Successful cultivation is the gold standard for identifying a virus, according to the Koch postulates. However, this requires screening for a permissive cell line, which is traditionally time-, reagent- and labor-intensive. Here, a simple and easy-to-operate microfluidic chip, formed by seeding a variety of cell lines and culturing them in parallel, is reported for use in virus cultivation and virus-permissive host-cell screening. The chip was tested by infection with two known viruses, enterovirus 71 (EV71) and influenza virus H1N1. Infection with EV71 and H1N1 caused significant cytopathic effects (CPE) in RD and MDCK cells, respectively, demonstrating that virus cultivation based on this microfluidic cell chip can be used as a substitute for the traditional plate-based culture method and reproduce the typical CPE caused by virus infection. Using this microfluidic cell chip method for virus cultivation could make it possible to identify an emerging virus in a high-throughput, automatic, and unprecedentedly fast way.

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    1. Alonso, F.V., Compans, R.W., 1981. Differential effect of monensin on enveloped viruses that form at distinct plasma membrane domains. J. Cell Biol. 89, 700–705.

    2. Bhatia, S.N., Ingber, D.E., 2014. Microfluidic organs-on-chips. Nat. Biotechnol. 32, 760–772.

    3. Bryan, W.R., 1957. Interpretation of host response in quantitative studies on animal viruses. Ann. N. Y. Acad. Sci. 69, 698–728.

    4. Drews, K., Calgi, M.P., Harrison, W.C., Drews, C.M., Costa-Pinheiro, P., Shaw, J.J.P., Jobe, K.A., Nelson, E.A., Han, J.D., Fox, T., White, J.M., Kester, M., 2019. Glucosylceramidase maintains influenza virus infection by regulating endocytosis. J. Virol. 93, e00017–19.

    5. Dudas, G., Carvalho, L.M., Bedford, T., Tatem, A.J., Baele, G., Faria, N.R., Park, D.J., Ladner, J.T., Arias, A., Asogun, D., Bielejec, F., Caddy, S.L., Cotten, M., D'Ambrozio, J., Dellicour, S., Di Caro, A., Diclaro, J.W., Duraffour, S., Elmore, M.J., Fakoli, L.S., Faye, O., Gilbert, M.L., Gevao, S.M., Gire, S., Gladden-Young, A., Gnirke, A., Goba, A., Grant, D.S., Haagmans, B.L., Hiscox, J.A., Jah, U., Kugelman, J.R., Liu, D., Lu, J., Malboeuf, C.M., Mate, S., Matthews, D.A., Matranga, C.B., Meredith, L.W., Qu, J., Quick, J., Pas, S.D., Phan, M.V.T., Pollakis, G., Reusken, C.B., Sanchez-Lockhart, M., Schaffner, S.F., Schieffelin, J.S., Sealfon, R.S., Simon-Loriere, E., Smits, S.L., Stoecker, K., Thorne, L., Tobin, E.A., Vandi, M.A., Watson, S.J., West, K., Whitmer, S., Wiley, M.R., Winnicki, S.M., Wohl, S., Wolfel, R., Yozwiak, N.L., Andersen, K.G., Blyden, S.O., Bolay, F., Carroll, M.W., Dahn, B., Diallo, B., Formenty, P., Fraser, C., Gao, G.F., Garry, R.F., Goodfellow, I., Gunther, S., Happi, C.T., Holmes, E.C., Kargbo, B., Keita, S., Kellam, P., Koopmans, M.P.G., Kuhn, J.H., Loman, N.J., Magassouba, N., Naidoo, D., Nichol, S.T., Nyenswah, T., Palacios, G., Pybus, O.G., Sabeti, P.C., Sall, A., Stroher, U., Wurie, I., Suchard, M.A., Lemey, P., Rambaut, A., 2017. Virus genomes reveal factors that spread and sustained the Ebola epidemic. Nature 544, 309–315.

    6. Farokhzad, N., Tao, W., 2021. Materials chemistry-enabled platforms in detecting sexually transmitted infections: progress towards point-of-care tests. Trends in Chemistry 3, 589–602.

    7. Fisch, H., Gifford, G.E., 1983. A photometric and plaque assay for macrophage mediated tumor cell cytotoxicity. J. Immunol. Methods 57, 311–325.

    8. Ganzenmueller, T., Kluba, J., Hilfrich, B., Puppe, W., Verhagen, W., Heim, A., Schulz, T., Henke-Gendo, C., 2010. Comparison of the performance of direct fluorescent antibody staining, a point-of-care rapid antigen test and virus isolation with that of RT-PCR for the detection of novel 2009 influenza A (H1N1) virus in respiratory specimens. J. Med. Microbiol. 59, 713–717.

    9. Guo, F., Li, S., Caglar, M.U., Mao, Z., Liu, W., Woodman, A., Arnold, J.J., Wilke, C.O., Huang, T.J., Cameron, C.E., 2017. Single-cell Virology: on-chip investigation of viral infection dynamics. Cell Rep. 21, 1692–1704.

    10. Hierholzer, J.C., Suggs, M.T., Hall, E.C., 1969. Standardized viral hemagglutination and hemagglutination-inhibition tests. II. Description and statistical evaluation. Appl.Microbiol. 18, 824–833.

    11. Hoffmann, M., Kleine-Weber, H., Schroeder, S., Kruger, N., Herrler, T., Erichsen, S., Schiergens, T.S., Herrler, G., Wu, N.H., Nitsche, A., Muller, M.A., Drosten, C., Pohlmann, S., 2020. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271–280 e278.

    12. Huang, S.B., Wang, S.S., Hsieh, C.H., Lin, Y.C., Lai, C.S., Wu, M.H., 2013. An integrated microfluidic cell culture system for high-throughput perfusion three-dimensional cell culture-based assays: effect of cell culture model on the results of chemosensitivity assays. Lab Chip 13, 1133–1143.

    13. Imai, M., Ninomiya, A., Minekawa, H., Notomi, T., Ishizaki, T., Tashiro, M., Odagiri, T., 2006. Development of H5-RT-LAMP (loop-mediated isothermal amplification) system for rapid diagnosis of H5 avian influenza virus infection. Vaccine 24, 6679–6682.

    14. Khan, F., Tare, R.S., Kanczler, J.M., Oreffo, R.O., Bradley, M., 2010. Strategies for cell manipulation and skeletal tissue engineering using high-throughput polymer blend formulation and microarray techniques. Biomaterials 31, 2216–2228.

    15. Ku, Z., Shi, J., Liu, Q., Huang, Z., 2012. Development of murine monoclonal antibodies with potent neutralization effects on enterovirus 71. J. Virol Methods 186, 193–197.

    16. Lee, W.C., Fuller, A.O., 1993. Herpes simplex virus type 1 and pseudorabies virus bind to a common saturable receptor on Vero cells that is not heparan sulfate. J. Virol. 67, 5088–5097.

    17. Leonardi, G.P., Mitrache, I., Pigal, A., Freedman, L., 2010. Public hospital-based laboratory experience during an outbreak of pandemic influenza A (H1N1) virus infections. J. Clin. Microbiol. 48, 1189–1194.

    18. Leong, P.W., Liew, K., Lim, W., Chow, V.T., 2002. Differential display RT-PCR analysis of enterovirus-71-infected rhabdomyosarcoma cells reveals mRNA expression responses of multiple human genes with known and novel functions. Virology 295, 147–159.

    19. Li, W., Moore, M.J., Vasilieva, N., Sui, J., Wong, S.K., Berne, M.A., Somasundaran, M., Sullivan, J.L., Luzuriaga, K., Greenough, T.C., Choe, H., Farzan, M., 2003. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426, 450–454.

    20. Liu, X., Feng, J., Zhang, Q., Guo, D., Zhang, L., Suo, T., Hu, W., Guo, M., Wang, X., Huang, Z., Xiong, Y., Chen, G., Chen, Y., Lan, K., 2020. Analytical comparisons of SARS-COV-2 detection by qRT-PCR and ddPCR with multiple primer/probe sets. Emerg. Microb. Infect. 9, 1175–1179.

    21. Lum, L.C., Chua, K.B., McMinn, P.C., Goh, A.Y., Muridan, R., Sarji, S.A., Hooi, P.S., Chua, B.H., Lam, S.K., 2002. Echovirus 7 associated encephalomyelitis. J. Clin. Virol. 23, 153–160.

    22. Mehling, M., Tay, S., 2014. Microfluidic cell culture. Curr. Opin. Biotechnol. 25, 95–102.

    23. Morrill, S., Gilbert, N.M., Lewis, A.L., 2020. Gardnerella vaginalis as a cause of bacterial vaginosis: appraisal of the evidence from in vivo models. Front. Cell. Infect.Microbiol. 10, 168.

    24. Nakauchi, M., Takayama, I., Takahashi, H., Tashiro, M., Kageyama, T., 2014. Development of a reverse transcription loop-mediated isothermal amplification assay for the rapid diagnosis of avian influenza A (H7N9) virus infection. J. Virol Methods 204, 101–104.

    25. Phanthanawiboon, S., An, A., Panngarm, N., Limkittikul, K., Ikuta, K., Anantapreecha, S., Kurosu, T., 2014. Isolation and propagation of Dengue virus in Vero and BHK-21 cells expressing human DC-SIGN stably. J. Virol Methods 209, 55–61.

    26. Puhl, A.C., Fritch, E.J., Lane, T.R., Tse, L.V., Yount, B.L., Sacramento, C.Q., FintelmanRodrigues, N., Tavella, T.A., Maranhao Costa, F.T., Weston, S., Logue, J., Frieman, M., Premkumar, L., Pearce, K.H., Hurst, B.L., Andrade, C.H., Levi, J.A., Johnson, N.J., Kisthardt, S.C., Scholle, F., Souza, T.M.L., Moorman, N.J., Baric, R.S., Madrid, P.B., Ekins, S., 2021. Repurposing the Ebola and marburg virus inhibitors tilorone, quinacrine, and pyronaridine: in vitro activity against SARS-CoV-2 and potential mechanisms. ACS Omega 6, 7454–7468.

    27. Ren, X., Yang, F., Hu, Y., Zhang, T., Liu, L., Dong, J., Sun, L., Zhu, Y., Xiao, Y., Li, L., Yang, J., Wang, J., Jin, Q., 2013. Full genome of influenza A (H7N9) virus derived by direct sequencing without culture. Emerg. Infect. Dis. 19, 1881–1884.

    28. Rivers, T.M., 1937. Viruses and koch's postulates. J. Bacteriol. 33, 1–12.

    29. Shen, C.F., Guilbault, C., Li, X., Elahi, S.M., Ansorge, S., Kamen, A., Gilbert, R., 2019. Development of suspension adapted Vero cell culture process technology for production of viral vaccines. Vaccine 37, 6996–7002.

    30. Shen, L., Wang, C., Zhao, J., Tang, X., Shen, Y., Lu, M., Ding, Z., Huang, C., Zhang, J., Li, S., Lan, J., Wong, G., Zhu, Y., 2020. Delayed specific IgM antibody responses observed among COVID-19 patients with severe progression. Emerg. Microb. Infect. 9, 1096–1101.

    31. Tang, Z., Kong, N., Zhang, X., Liu, Y., Hu, P., Mou, S., Liljestrom, P., Shi, J., Tan, W., Kim, J.S., Cao, Y., Langer, R., Leong, K.W., Farokhzad, O.C., Tao, W., 2020. A materials-science perspective on tackling COVID-19. Nat. Rev. Mater. 5, 847–860.

    32. Tobias-Altura, M.C., Ngelangel, C.A., 2022. In vitro anti-viral activity of hexetidine(Bactidol®) oral mouthwash against human coronavirus OC43 and influenza A (H1N1) virus. Philippine Journal of Health Research and Development 26, 1–6.

    33. Tong, Y.G., Shi, W.F., Liu, D., Qian, J., Liang, L., Bo, X.C., Liu, J., Ren, H.G., Fan, H., Ni, M., Sun, Y., Jin, Y., Teng, Y., Li, Z., Kargbo, D., Dafae, F., Kanu, A., Chen, C.C., Lan, Z.H., Jiang, H., Luo, Y., Lu, H.J., Zhang, X.G., Yang, F., Hu, Y., Cao, Y.X., Deng, Y.Q., Su, H.X., Sun, Y., Liu, W.S., Wang, Z., Wang, C.Y., Bu, Z.Y., Guo, Z.D., Zhang, L.B., Nie, W.M., Bai, C.Q., Sun, C.H., An, X.P., Xu, P.S., Zhang, X.L., Huang, Y., Mi, Z.Q., Yu, D., Yao, H.W., Feng, Y., Xia, Z.P., Zheng, X.X., Yang, S.T., Lu, B., Jiang, J.F., Kargbo, B., He, F.C., Gao, G.F., Cao, W.C., China Mobile Laboratory Testing Team in Sierra L, 2015. Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone. Nature 524, 93–96.

    34. Wang, G., Zhang, J., Li, W., Xin, G., Su, Y., Gao, Y., Zhang, H., Lin, G., Jiao, X., Li, K., 2008. Apoptosis and proinflammatory cytokine responses of primary mouse microglia and astrocytes induced by human H1N1 and avian H5N1 influenza viruses. Cell. Mol. Immunol. 5, 113–120.

    35. Warrick, J.W., Timm, A., Swick, A., Yin, J., 2016. Tools for single-cell kinetic analysis of virus-host interactions. PLoS One 11, e0145081.

    36. Wen, Y., Zhang, X., Yang, S.T., 2010. Microplate-reader compatible perfusion microbioreactor array for modular tissue culture and cytotoxicity assays. Biotechnol. Prog. 26, 1135–1144.

    37. Wu, F., Zhao, S., Yu, B., Chen, Y.M., Wang, W., Song, Z.G., Hu, Y., Tao, Z.W., Tian, J.H., Pei, Y.Y., Yuan, M.L., Zhang, Y.L., Dai, F.H., Liu, Y., Wang, Q.M., Zheng, J.J., Xu, L., Holmes, E.C., Zhang, Y.Z., 2020. A new coronavirus associated with human respiratory disease in China. Nature 579, 265–269.

    38. Xiao, J., Zhang, Y., Hong, M., Han, Z., Zhang, M., Song, Y., Yan, D., Zhu, S., Xu, W., 2020. Phylogenetic characteristics and molecular epidemiological analysis of novel enterovirus EV-B83 isolated from Tibet, China. Sci. Rep. 10, 6630.

    39. Yi, L., He, Y., Chen, Y., Kung, H.F., He, M.L., 2011. Potent inhibition of human enterovirus 71 replication by type I interferon subtypes. Antivir. Ther. 16, 51–58.

    40. Yu, Y., Wang, Q., Wang, C., Shang, L., 2021. Living materials for regenerative medicine. Engineered Regeneration 2, 96–104.

    41. Zhang, D., Bian, F., Cai, L., Wang, T., Kong, T., Zhao, Y., 2019. Bioinspired photonic barcodes for multiplexed target cycling and hybridization chain reaction. Biosens. Bioelectron. 143, 111629.

    42. Zhang, H., Chen, G., Yu, Y., Guo, J., Tan, Q., Zhao, Y., 2020. Microfluidic printing of slippery textiles for medical drainage around wounds. Adv. Sci. 7, 2000789.

    43. Zhou, P., Yang, X.L., Wang, X.G., Hu, B., Zhang, L., Zhang, W., Si, H.R., Zhu, Y., Li, B., Huang, C.L., Chen, H.D., Chen, J., Luo, Y., Guo, H., Jiang, R.D., Liu, M.Q., Chen, Y., Shen, X.R., Wang, X., Zheng, X.S., Zhao, K., Chen, Q.J., Deng, F., Liu, L.L., Yan, B., Zhan, F.X., Wang, Y.Y., Xiao, G.F., Shi, Z.L., 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273.

    44. Zhou, X., Zhao, J., Zheng, D., Yu, Y., Liu, L., 2021. Agent-based simulation of virus testing in certain-exposure time through community health service centers' evaluation-A case study of wuhan. Healthcare (Basel) 9, 1519.

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    A microfluidic cell chip for virus isolation via rapid screening for permissive cells

      Corresponding author: Xian-En Zhang, zhangxe@ibp.ac.cn
      Corresponding author: Yong He, yongqin@zju.edu.cn
      Corresponding author: Feng Li, fli@wh.iov.cn
    • a State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China;
    • b School of Mechanics and Safety Engineering, Zhengzhou University, Zhengzhou, 450001, China;
    • c Faculty of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China;
    • d National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China;
    • e State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China;
    • f University of Chinese Academy of Sciences, Beijing, 100049, China;
    • g Current address:Wuhan Institute of Biological Products Co., Ltd., Wuhan, 430070, China

    Abstract: Virus identification is a prerequisite not only for the early diagnosis of viral infectious diseases but also for the effective prevention of epidemics. Successful cultivation is the gold standard for identifying a virus, according to the Koch postulates. However, this requires screening for a permissive cell line, which is traditionally time-, reagent- and labor-intensive. Here, a simple and easy-to-operate microfluidic chip, formed by seeding a variety of cell lines and culturing them in parallel, is reported for use in virus cultivation and virus-permissive host-cell screening. The chip was tested by infection with two known viruses, enterovirus 71 (EV71) and influenza virus H1N1. Infection with EV71 and H1N1 caused significant cytopathic effects (CPE) in RD and MDCK cells, respectively, demonstrating that virus cultivation based on this microfluidic cell chip can be used as a substitute for the traditional plate-based culture method and reproduce the typical CPE caused by virus infection. Using this microfluidic cell chip method for virus cultivation could make it possible to identify an emerging virus in a high-throughput, automatic, and unprecedentedly fast way.

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