title: ERK- and JNK-dependent signaling pathways contribute to Bombyx mori nucleopolyhedrovirus infection.
abstract: Mitogen-activated protein kinases (MAPKs) often play important roles in virus infection. To explore intracellular signaling pathways induced by baculovirus infection, we examined the involvement of MAPKs in Bombyx mori nucleopolyhedrovirus (BmNPV) infection of BmN cells. We found that specific inhibitors of extracellular signal-regulated kinase (ERK) kinase and c-Jun NH(2)-terminal kinase (JNK) significantly reduced occlusion body (OB) formation and budded virus (BV) production. Next, we quantified OB and BV production after applying the inhibitors at different times postinfection (p.i.). The inhibitors significantly reduced OB and BV production to various extents when applied at 12 h p.i., indicating that the reduction of BmNPV infectivity by these inhibitors occurs at the late stage of infection. Also, we observed that these inhibitors markedly repressed or deregulated the expression of delayed early, late, and very late gene products. Western blot analysis using phospho-MAPK-specific antibodies showed that ERK and JNK were activated at the late stage of BmNPV infection. In addition, the magnitude and pattern of MAPK activation were dependent on the multiplicity of infection. To verify the effects of the inhibitors on BmNPV infection, we also attempted to knock down the B. mori genes BmErk and BmJnk, which encode ERK and JNK, respectively. Knockdown of BmErk and BmJnk resulted in the reduced production of OBs and BVs, confirming that BmERK and BmJNK are involved in the BmNPV infection process. Taken together, these results indicate that the activation of MAPK signaling pathways is required for efficient infection by BmNPV.
authors.affiliation: Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan. katsuma@ss.ab.a.u-tokyo.ac.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Katsuma
authors.forename: Kazuei
authors.initials: K
authors.lastname: Mita
authors.forename: Toru
authors.initials: T
authors.lastname: Shimada
mesh_terms: D000818:Animals; D012831:Bombyx / Q000201:enzymology / Q000821:virology*; D002460:Cell Line; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017924:Nucleopolyhedroviruses / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D014764:Viral Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases