Rabies virus dissemination in neural tissues of autopsy cases due to rabies imported into Japan from the Philippines: immunohistochemistry.
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.
Tobiume
Minoru
M
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Sato
Yuko
Y
Katano
Harutaka
H
Nakajima
Noriko
N
Tanaka
Keiko
K
Noguchi
Akira
A
Inoue
Satoshi
S
Hasegawa
Hideki
H
Iwasa
Yoko
Y
Tanaka
Junichi
J
Hayashi
Hiroyuki
H
Yoshida
Sachiko
S
Kurane
Ichiro
I
Sata
Tetsutaro
T
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
D000956:Antigens, Viral