title: The pathogenesis of 3 neurotropic flaviviruses in a mouse model depends on the route of neuroinvasion after viremia.
abstract: Neurotropic flavivirus infection of humans results in viremia subsequently; in some cases, it causes meningitis encephalomyelitis, although the pathways from viremia to central nervous system (CNS) invasion are uncertain. Here, we intravenously infected BALB/c mice with 3 neurotropic flaviviruses, then examined the clinical manifestations and histopathologic changes. The Sofjin strain of tick-borne encephalitis virus-infected mice exhibited dose-dependent survival. The animals showed distention of the small intestine caused by peripheral neuritis because of infection of the myenteric plexus. Histopathologically, the strongly neurotropic Sofjin strain invaded the CNS of viremic mice via the autonomic nerves running from the plexus. The JaTH-160 strain of Japanese encephalitis virus was isolated from the lymph nodes during the preclinical phase of viral encephalitis. Therefore, this strain might infect the CNS via a hematogenous pathway, including through lymphoid tissues. The NY99-6922 strain of the West Nile virus caused clinical signs suggestive of intestinal, lymphoid, and/or neurologic involvement; the infected mice had prolonged viremia, suggesting that NY99-6922 may mainly use the hematogenous pathway; however, there was also histopathologic evidence of involvement of the autonomic nervous system pathway. In conclusion, the three neurotropic flaviviruses showed different pathogenesis, which were dependent upon overlapping but distinct pathways to CNS invasion after viremia.
authors: From the Departments of Pathology (NN, NI-Y, YS, AK, TS, HH) and Virology 1 (TT, IK), National Institute of Infectious Diseases, Tokyo; Department of Virology, Institute of Tropical Medicine, GCOE Program, Leading Graduate School Program, Nagasaki University, Nagasaki (DH); and Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido (HK, IT), Japan.
authors: Noriyo
authors: N
authors: Nagata
authors: Naoko
authors: N
authors: Iwata-Yoshikawa
authors: Daisuke
authors: D
authors: Hayasaka
authors: Yuko
authors: Y
authors: Sato
authors: Asato
authors: A
authors: Kojima
authors: Hiroaki
authors: H
authors: Kariwa
authors: Ikuo
authors: I
authors: Takashima
authors: Tomohiko
authors: T
authors: Takasaki
authors: Ichiro
authors: I
authors: Kurane
authors: Tetsutaro
authors: T
authors: Sata
authors: Hideki
authors: H
authors: Hasegawa
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000473:pathology* / Q000821:virology*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004195:Disease Models, Animal; D004669:Encephalitis Viruses, Tick-Borne / Q000302:isolation & purification; D005260:Female; D005416:Flavivirus / Q000302:isolation & purification; D018177:Flavivirus Infections / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014709:Vero Cells; D014766:Viremia / Q000473:pathology*