title: Rabies virus dissemination in neural tissues of autopsy cases due to rabies imported into Japan from the Philippines: immunohistochemistry.
abstract: Two Japanese men, 65 and 69 years old, developed rabies in Japan around 2-3 months after dog-bite exposure in the Philippines. Laboratory diagnosis of rabies was made following the detection of rabies virus genome on reverse transcription-polymerase chain reaction from saliva, and on immunohistochemistry of a nuchal skin punch biopsy in one case. The patients died 9 and 19 days after clinical onset. At autopsy, no macroscopic changes in the CNS were observed. Histopathology indicated that eosinophilic and cytoplasmic inclusion bodies, Negri bodies, were seen in neuronal cells of the CNS. Inflammatory cell reactions were scarce, and no apoptosis in the CNS was detected. Immunohistochemistry demonstrated that rabies virus nucleoprotein (N) and phosphoprotein (P) were disseminated to all neural tissues and cells in the body with a similar pattern in both cases. Interestingly, there were no differences of localization between N and P antigen in the brain, but the N antigen was located at the peripheral nerve sheaths and the P antigen was localized in axons. These data indicate that rabies virus dissemination in all neural tissues causes disease development and death. Immunohistochemistry for rabies is a powerful tool to understand the pathogenesis of rabies.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tobiume
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.forename: Harutaka
authors.initials: H
authors.lastname: Katano
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakajima
authors.forename: Keiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Akira
authors.initials: A
authors.lastname: Noguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iwasa
authors.forename: Junichi
authors.initials: J
authors.lastname: Tanaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yoshida
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurane
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
mesh_terms: D000368:Aged; D000818:Animals; D000956:Antigens, Viral; D001344:Autopsy; D001733:Bites and Stings / Q000150:complications*; D004285:Dogs; D017809:Fatal Outcome; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007564:Japan; D008297:Male; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000473:pathology / Q000821:virology*; D010679:Philippines; D011818:Rabies / Q000209:etiology / Q000473:pathology / Q000821:virology*; D011820:Rabies virus / Q000302:isolation & purification*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012463:Saliva / Q000821:virology
chemical_list: D000956:Antigens, Viral