Neuropathogenicity of Two Saffold Virus Type 3 Isolates in Mouse Models
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 men...
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| Published in | PloS one Vol. 11; no. 2; p. e0148184 |
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| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Public Library of Science
01.02.2016
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| Abstract | 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. |
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| AbstractList | 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. 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. 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. 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. Saffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the neuropathogenicity of SAFV remains undetermined.OBJECTIVESaffold 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.METHODSThe 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.RESULTSThe 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.CONCLUSIONSBoth 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. |
| Audience | Academic |
| Author | Sato, Yuko Suzuki, Tadaki Kozawa, Kunihisa Tsukagoshi, Hiroyuki Naeem, Asif Nagata, Noriyo Shimizu, Hiroyuki Nakajima, Noriko Iwata-Yoshikawa, Naoko Kotani, Osamu Taguchi, Fumihiro Hosomi, Takushi Hasegawa, Hideki |
| AuthorAffiliation | 2 Department of Virology and Viral Infections, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo, Japan 5 Gunma Prefectural Institute of Public Health and Environmental Sciences, Gunma, Japan 4 The Public Health Institute of Kochi Prefecture, Kochi, Japan 3 Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan University of Utah, UNITED STATES 1 Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan |
| AuthorAffiliation_xml | – name: 3 Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan – name: 5 Gunma Prefectural Institute of Public Health and Environmental Sciences, Gunma, Japan – name: University of Utah, UNITED STATES – name: 1 Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan – name: 2 Department of Virology and Viral Infections, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo, Japan – name: 4 The Public Health Institute of Kochi Prefecture, Kochi, Japan |
| Author_xml | – sequence: 1 givenname: Osamu surname: Kotani fullname: Kotani, Osamu – sequence: 2 givenname: Asif surname: Naeem fullname: Naeem, Asif – sequence: 3 givenname: Tadaki surname: Suzuki fullname: Suzuki, Tadaki – sequence: 4 givenname: Naoko surname: Iwata-Yoshikawa fullname: Iwata-Yoshikawa, Naoko – sequence: 5 givenname: Yuko surname: Sato fullname: Sato, Yuko – sequence: 6 givenname: Noriko surname: Nakajima fullname: Nakajima, Noriko – sequence: 7 givenname: Takushi surname: Hosomi fullname: Hosomi, Takushi – sequence: 8 givenname: Hiroyuki surname: Tsukagoshi fullname: Tsukagoshi, Hiroyuki – sequence: 9 givenname: Kunihisa surname: Kozawa fullname: Kozawa, Kunihisa – sequence: 10 givenname: Hideki surname: Hasegawa fullname: Hasegawa, Hideki – sequence: 11 givenname: Fumihiro surname: Taguchi fullname: Taguchi, Fumihiro – sequence: 12 givenname: Hiroyuki surname: Shimizu fullname: Shimizu, Hiroyuki – sequence: 13 givenname: Noriyo surname: Nagata fullname: Nagata, Noriyo |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26828718$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1371_journal_pntd_0006076 crossref_primary_10_1002_rmv_1908 crossref_primary_10_1186_s12985_016_0654_8 crossref_primary_10_1016_j_meegid_2017_05_005 crossref_primary_10_1099_jgv_0_000452 crossref_primary_10_1002_mus_27812 crossref_primary_10_1038_s41467_024_50921_w crossref_primary_10_1128_JVI_00864_16 crossref_primary_10_1093_jnen_nlz124 crossref_primary_10_23736_S2724_5276_18_05219_2 |
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| Copyright | COPYRIGHT 2016 Public Library of Science 2016 Kotani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2016 Kotani et al 2016 Kotani et al |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Current address: The Meat Inspection Center of Kochi Prefecture, Kochi, Japan Conceived and designed the experiments: OK FT HS N. Nagata. Performed the experiments: OK AN TS NI-Y YS N. Nakajima TH HT N. Nagata. Analyzed the data: OK TS NI-Y KK HH FT HS N. Nagata. Contributed reagents/materials/analysis tools: AN TH HT KK HS. Wrote the paper: OK NI-Y FT HS N. Nagata. Current address: Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan |
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| Snippet | Saffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the... Objective Saffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the... Objective Saffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the... |
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| SubjectTerms | 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 |
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| Title | Neuropathogenicity of Two Saffold Virus Type 3 Isolates in Mouse Models |
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