title: Heat shock protein 70 is related to thermal inhibition of nuclear export of the influenza virus ribonucleoprotein complex.
abstract: The influenza virus genome replicates and forms a viral ribonucleoprotein complex (vRNP) with nucleoprotein (NP) and RNA polymerases in the nuclei of host cells. vRNP is then exported into the cytoplasm for viral morphogenesis at the cell membrane. Matrix protein 1 (M1) and nonstructural protein 2/nuclear export protein (NS2/NEP) work in the nuclear export of vRNP by associating with it. It was previously reported that influenza virus production was inhibited in Madin-Darby canine kidney (MDCK) cells cultured at 41 degrees C because nuclear export of vRNP was blocked by the dissociation of M1 from vRNP (A. Sakaguchi, E. Hirayama, A. Hiraki, Y. Ishida, and J. Kim, Virology 306:244-253, 2003). Previous data also suggested that a certain protein(s) synthesized only at 41 degrees C inhibited the association of M1 with vRNP. The potential of heat shock protein 70 (HSP70) as a candidate obstructive protein was investigated. Induction of HSP70 by prostaglandin A1 (PGA1) at 37 degrees C caused the suppression of virus production. The nuclear export of viral proteins was inhibited by PGA1, and M1 was not associated with vRNP, indicating that HSP70 prevents M1 from binding to vRNP. An immunoprecipitation assay showed that HSP70 was bound to vRNP, suggesting that the interaction of HSP70 with vRNP is the reason for the dissociation of M1. Moreover, NS2 accumulated in the nucleoli of host cells cultured at 41 degrees C, showing that the export of NS2 was also disturbed at 41 degrees C. However, NS2 was exported normally from the nucleus, irrespective of PGA1 treatment at 37 degrees C, suggesting that HSP70 does not influence NS2.
authors.affiliation: Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University, 1, Shichonocho, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Hirayama
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Atagi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hiraki
authors.forename: Jeman
authors.initials: J
authors.lastname: Kim
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004285:Dogs; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006384:Hemagglutination; D006358:Hot Temperature; D009980:Influenza A virus / Q000378:metabolism* / Q000502:physiology; D011454:Prostaglandins A / Q000494:pharmacology; D012261:Ribonucleoproteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D011454:Prostaglandins A; D012261:Ribonucleoproteins; D014764:Viral Proteins; C100573:prostaglandin A1