Forskolin increases propagation of influenza virus in Madin-Darby canine kidney cells (VAC5P.1118)

Abstract

Abstract Influenza virus is a pathogenic negative-sense RNA virus belonging to the Orthomyxoviridae, which causes severe respiratory illness worldwide. A vaccine against the influenza virus is the best way to control the spread of influenza. Recently, a cell-based influenza vaccine was developed to overcome the disadvantages of egg-based vaccines. Here, we investigated whether forskolin, an adenylyl cyclase activator, could increase the output of the cell-based influenza vaccine. We found that forskolin increased the propagation of three influenza virus subtypes, A/H1N1/California/4/09, A/H3N2/Mississippi/1/85, and B/Shandong/7/97, in MDCK cells. We performed a microarray analysis to identify the mechanism whereby forskolin enhances influenza virus replication. We compared a forskolin-treated group with untreated group after infection with influenza virus. The expression of importin α5 and Erk1/2, which can regulate the import and export of viral ribonucleoprotein complex (vRNP), is upregulated in the forskolin-treated group. By contrast, the expression of innate immunity factors and antiviral factors such as TLR3, RIG-I/MDA5, IRF3, MxA and viperin, is downregulated. Taken together, we suggest the reduction of the antiviral response and the increase of translocation of vRNP by forskolin enhance the propagation of influenza virus. Therefore, the addition of forskolin to cultures may be helpful to increase the production efficiency of cell-based vaccines for influenza virus.