title: Cyclosporin A inhibits the propagation of influenza virus by interfering with a late event in the virus life cycle.
abstract: Influenza is a global public health problem that causes a serious respiratory disease. Influenza virus frequently undergoes amino acid substitutions, which result in the emergence of drug-resistant viruses. To control influenza viruses that are resistant to currently available drugs, it is essential to develop new antiviral drugs with a novel molecular target. Here, we report that cyclosporin A (CsA) inhibits the propagation of influenza virus in A549 cells by interfering with a late event in the virus life cycle. CsA did not affect adsorption, internalization, viral RNA replication, or synthesis of viral proteins in A549 cells, but inhibited the step(s) after viral protein synthesis, such as assembly or budding. In addition, siRNA-mediated knockdown of the expression of the major CsA targets, namely cyclophilin A (CypA), cyclophilin B (CypB), and P-glycoprotein (Pgp), did not inhibit influenza virus propagation. These results suggest that CsA inhibits virus propagation by mechanism(s) independent of the inhibition of the function of CypA, CypB, and Pgp. CsA may target an unknown molecule that works as a positive regulator in the propagation of influenza virus. Our findings would contribute to the development of a novel anti-influenza virus therapy and clarification of the regulatory mechanism of influenza virus multiplication.
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Itsuki
authors.initials: I
authors.lastname: Hamamoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Harazaki
authors.forename: Naohiko
authors.initials: N
authors.lastname: Inase
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaku
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology*; D019065:Virus Assembly / Q000187:drug effects*; D057074:Virus Release / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D016572:Cyclosporine