title: Neuropathogenicity of Two Saffold Virus Type 3 Isolates in Mouse Models.
abstract: OBJECTIVE
  Saffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the neuropathogenicity of SAFV remains undetermined.
  
  
  METHODS
  The virulence of two clinical isolates of SAFV type 3 (SAFV-3) obtained from a patient with aseptic meningitis (AM strain) and acute upper respiratory inflammation (UR strain) was analyzed in neonatal and young mice utilizing virological, pathological, and immunological methods.
  
  
  RESULTS
  The polyproteins of the strains differed in eight amino acids. Both clinical isolates were infective, exhibited neurotropism, and were mildly neurovirulent in neonatal ddY mice. Both strains pathologically infected neural progenitor cells and glial cells, but not large neurons, with the UR strain also infecting epithelial cells. UR infection resulted in longer inflammation in the brain and spinal cord because of demyelination, while the AM strain showed more infectivity in the cerebellum in neonatal ddY mice. Additionally, young BALB/c mice seroconverted following mucosal inoculation with the UR, but not the AM, strain.
  
  
  CONCLUSIONS
  Both SAFV-3 isolates had neurotropism and mild neurovirulence but showed different cell tropisms in both neonatal and young mouse models. This animal model has the potential to recapitulate the potential neuropathogenicity of SAFV-3.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.|Department of Virology and Viral Infections, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kotani
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Asif
authors.initials: A
authors.lastname: Naeem
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Tadaki
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwata-Yoshikawa
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakajima
authors.affiliation: The Public Health Institute of Kochi Prefecture, Kochi, Japan.
authors.forename: Takushi
authors.initials: T
authors.lastname: Hosomi
authors.affiliation: Gunma Prefectural Institute of Public Health and Environmental Sciences, Gunma, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsukagoshi
authors.affiliation: Gunma Prefectural Institute of Public Health and Environmental Sciences, Gunma, Japan.
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Kozawa
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Virology and Viral Infections, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Taguchi
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001835:Body Weight; D001921:Brain / Q000473:pathology* / Q000821:virology*; D017943:Cardiovirus / Q000276:immunology / Q000302:isolation & purification* / Q000472:pathogenicity*; D018188:Cardiovirus Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*; D003711:Demyelinating Diseases / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007109:Immunity; D007249:Inflammation / Q000473:pathology; D007276:Injections, Intraventricular; D007370:Interferon Type I / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000473:pathology / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction; D018523:Tropism; D014774:Virulence; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000956:Antigens, Viral; D007370:Interferon Type I
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