title: Differential activation of the c-Jun N-terminal kinase/stress-activated protein kinase and p38 mitogen-activated protein kinase signal transduction pathways in the mouse brain upon infection with neurovirulent influenza A virus.
abstract: The temporal and spatial distribution of active c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in the brain was investigated in an experimental virus-mouse system in which neurovirulent influenza A virus caused lethal acute encephalitis. Following stereotaxic microinjection into the olfactory bulb, virus-infected neurons appeared in several midbrain structures, including the ventral tegmental area, amygdala and the pyramidal layer of the hippocampus. Infected neurons exhibited apoptosis on day 5, as demonstrated by in situ detection of DNA fragmentation and active caspase-3. The stress-responsive JNK signal transduction pathway was activated in virus-infected neurons. Activation of p38 MAPK was widespread and occurred in astrocytes on day 7 after infection. Active p38 MAPK in astrocytes showed no association with apoptosis but appeared to be involved in regulation of TNF-alpha production. These results indicate that these two stress-activated protein kinases may play distinct roles during the course of lethal acute influenza virus encephalitis.
authors.affiliation: Department of Microbiology, Fukui Medical University School of Medicine, 23-3 Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.|Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi, Japan.|Department of Microbiology and Immunology, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Mori
authors.affiliation: Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi, Japan.
authors.forename: Fumi
authors.initials: F
authors.lastname: Goshima
authors.affiliation: Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Koshizuka
authors.affiliation: Department of Microbiology and Immunology, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Koide
authors.affiliation: Department of Microbiology and Immunology, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Department of Microbiology and Immunology, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Microbiology and Immunology, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
authors.affiliation: Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nishiyama
authors.affiliation: Department of Microbiology, Fukui Medical University School of Medicine, 23-3 Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kimura
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000821:virology; D005260:Female; D009980:Influenza A virus / Q000472:pathogenicity*; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000821:virology; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases