Journal of Microbiology and Biotechnology

  • 제33권12호
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  • Pages.1576-1586
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  • 2023
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  • 1017-7825(pISSN)
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  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
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The Adenylyl Cyclase Activator Forskolin Increases Influenza Virus Propagation in MDCK Cells by Regulating ERK1/2 Activity

  • Sang-Yeon Lee (Department of Medical and Biological Sciences, The Catholic University of Korea) ;
  • Jisun Lee (Department of Medical and Biological Sciences, The Catholic University of Korea) ;
  • Hye-Lim Park (Department of Medical and Biological Sciences, The Catholic University of Korea) ;
  • Yong-Wook Park (Department of R&D, SK Bioscience) ;
  • Hun Kim (Department of R&D, SK Bioscience) ;
  • Jae-Hwan Nam (Department of Medical and Biological Sciences, The Catholic University of Korea)
  • 투고 : 2023.06.12
  • 심사 : 2023.08.28
  • 발행 : 2023.12.28
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초록

Vaccination is the most effective method for preventing the spread of the influenza virus. Cell-based influenza vaccines have been developed to overcome the disadvantages of egg-based vaccines and their production efficiency has been previously discussed. In this study, we investigated whether treatment with forskolin (FSK), an adenylyl cyclase activator, affected the output of a cell-based influenza vaccine. We found that FSK increased the propagation of three influenza virus subtypes (A/H1N1/California/4/09, A/H3N2/Mississippi/1/85, and B/Shandong/7/97) in Madin-Darby canine kidney (MDCK) cells. Interestingly, FSK suppressed the growth of MDCK cells. This effect could be a result of protein kinase A (PKA)-Src axis activation, which downregulates extracellular signal-regulated kinase (ERK)1/2 activity and delays cell cycle progression from G1 to S. This delay in cell growth might benefit the binding and entry of the influenza virus in the early stages of viral replication. In contrast, FSK dramatically upregulated ERK1/2 activity via the cAMP-PKA-Raf-1 axis at a late stage of viral replication. Thus, increased ERK1/2 activity might contribute to increased viral ribonucleoprotein export and influenza virus propagation. The increase in viral titer induced by FSK could be explained by the action of cAMP in assisting the entry and binding of the influenza virus. Therefore, FSK addition to cell culture systems could help increase the production efficiency of cell-based vaccines against the influenza virus.

키워드

과제정보

We thank the members of the Laboratory of Viral Immunology for helpful discussions and technical assistance. This study was supported by a grant from SK Bioscience (grant number M-2023-D0731-00001), as well as by a National Research Foundation of Korea grant (grant number NRF-2021M3E5E3080558), Ministry of Food and Drug Safety grant (grant number 22213MFDS421), and Catholic University of Korea Research Fund, 2022.

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