Neuropathogenicity of Two Saffold Virus Type 3 Isolates in Mouse Models

• Published in: PloS one Vol. 11; no. 2; p. e0148184
• Main Authors: Kotani, Osamu, Naeem, Asif, Suzuki, Tadaki, Iwata-Yoshikawa, Naoko, Sato, Yuko, Nakajima, Noriko, Hosomi, Takushi, Tsukagoshi, Hiroyuki, Kozawa, Kunihisa, Hasegawa, Hideki, Taguchi, Fumihiro, Shimizu, Hiroyuki, Nagata, Noriyo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2016; Public Library of Science (PLoS)
• Subjects: Adaptation; Amino Acid Sequence; Amino acids; Animal models; Animals; Animals, Newborn; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antigens, Viral - immunology; Aseptic meningitis; Binding sites; Biology and Life Sciences; Body Weight; Brain; Brain - pathology; Brain - virology; Cardiovirus - immunology; Cardiovirus - isolation & purification; Cardiovirus - pathogenicity; Cardiovirus Infections - genetics; Cardiovirus Infections - immunology; Cardiovirus Infections - pathology; Cardiovirus Infections - virology; Cells (biology); Cerebellum; Children; Clinical isolates; Demyelinating Diseases - pathology; Demyelination; Development and progression; Disease Models, Animal; Disease Progression; Encephalitis; Enterovirus; Environmental science; Epithelial cells; Female; Genetic aspects; Glial cells; Glial stem cells; Health surveillance; Immunity; Immunology; Infections; Infectious diseases; Infectivity; Inflammation; Inflammation - pathology; Injections, Intraventricular; Inoculation; Interferon Type I - metabolism; Life sciences; Medicine and Health Sciences; Meningitis; Mice; Mice, Inbred BALB C; Mucosa; Mucous Membrane - pathology; Mucous Membrane - virology; Neonates; Neural stem cells; Neurological disorders; Neuronal-glial interactions; Neurons; Neuropathology; Neurotropism; Neurovirulence; Newborn babies; Paralysis; Pathology; Physiological aspects; Picornaviridae; Picornavirus infections; Picornaviruses; Poliomyelitis; Polyproteins; Proteins; Public health; Real-Time Polymerase Chain Reaction; Research and Analysis Methods; Rodents; Spinal cord; Strains (organisms); Surveillance; Tropism; Veterinary medicine; Viral infections; Virology; Virulence; Virus Replication; Viruses; West Nile virus; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0148184

Saffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the neuropathogenicity of SAFV remains undetermined. 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. 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. 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.