Evaluation of a mouse model for the West Nile virus group for the purpose of determining viral pathotypes.
Abstract: West Nile virus (WNV; family Flaviviridae; genus Flavivirus) group members are an important cause of viral meningoencephalitis in some areas of the world. They exhibit marked variation in pathogenicity, with some viral lineages (such as those from North America) causing high prevalence of severe neurological disease, whilst others (such as Australian Kunjin virus) rarely cause disease. The aim of this study was to characterize WNV disease in a mouse model and to elucidate the pathogenetic features that distinguish disease variation. Tenfold dilutions of five WNV strains (New York 1999, MRM16 and three horse isolates of WNV-Kunjin: Boort and two isolates from the 2011 Australian outbreak) were inoculated into mice by the intraperitoneal route. All isolates induced meningoencephalitis in different proportions of infected mice. WNVNY99 was the most pathogenic, the three horse isolates were of intermediate pathogenicity and WNVKUNV-MRM16 was the least, causing mostly asymptomatic disease with seroconversion. Infectivity, but not pathogenicity, was related to challenge dose. Using cluster analysis of the recorded clinical signs, histopathological lesions and antigen distribution scores, the cases could be classified into groups corresponding to disease severity. Metrics that were important in determining pathotype included neurological signs (paralysis and seizures), meningoencephalitis, brain antigen scores and replication in extra-neural tissues. Whereas all mice infected with WNVNY99 had extra-neural antigen, those infected with the WNV-Kunjin viruses only occasionally had antigen outside the nervous system. We conclude that the mouse model could be a useful tool for the assessment of pathotype for WNVs.
© 2014 CSIRO.
Publication Date: 2014-04-02 PubMed ID: 24694397DOI: 10.1099/vir.0.063537-0Google Scholar: Lookup
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- Journal Article
Summary
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The aim of the research article was to characterize variations in disease caused by different strains of West Nile Virus (WNV) using a mouse model. The research findings indicate that the mouse model can be a useful tool for evaluating the severity of WNV pathotypes.
Study Design and Methodology
- The study involved five different WNV strains. These include New York 1999, MRM16, and three strains (Boort and two selected from the 2011 Australian outbreak) of an Australian variant of WNV known as Kunjin virus.
- Each of these strains was diluted tenfold and then inoculated into mice intraperitoneally.
- The impact of different strains on infected mice was analyzed with a focus on the proportions that developed one severe condition caused by WNV, meningoencephalitis.
Findings and Observations
- All the introduced WNV strains led to meningoencephalitis but in varying proportions.
- The most pathogenic strain was WNVNY99, while WNVKUNV-MRM16 caused mainly asymptomatic disease with seroconversion, marking it as the least pathogenic.
- The three horse isolates exhibited intermediate pathogenicity.
- The study revealed that the infectivity of the virus was associated with the challenge dose and not the pathogenicity.
Classification and Determination of Pathotypes
- Using clinical signs, histopathological lesions, and antigen distribution scores, the researchers classified the cases into groups that corresponded to the disease’s severity.
- Key metrics in identifying pathotype included the presence of neurological signs like paralysis and seizures, meningoencephalitis, brain antigen scores, and replication of the virus in extra-neural tissues.
- Extra-neural antigen was present in all mice infected with WNVNY99, while it was seldom observed in mice infected with WNV-Kunjin.
Conclusion and Implications
- The findings demonstrate that a mouse model could be a valuable tool in assessing the pathotype for different WNV strains.
- Further studies using this model could enhance our understanding of various factors influencing the severity of WNV diseases and possibly contribute to the development of more effective prevention and treatment strategies.
Cite This Article
APA
Bingham J, Payne J, Harper J, Frazer L, Eastwood S, Wilson S, Lowther S, Lunt R, Warner S, Carr M, Hall RA, Durr PA.
(2014).
Evaluation of a mouse model for the West Nile virus group for the purpose of determining viral pathotypes.
J Gen Virol, 95(Pt 6), 1221-1232.
https://doi.org/10.1099/vir.0.063537-0 Publication
Researcher Affiliations
- Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
- Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
- Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
- Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
- Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
- Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
- Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
- Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
- Biosciences Research Division, Department of Environment and Primary Industries Victoria, AgriBio Centre, 5 Ring Road, La Trobe University Campus, Bundoora, Victoria 3083, Australia.
- Biosecurity SA, Primary Industries and Regions South Australia, GPO Box 1671, Adelaide, South Australia 5001, Australia.
- Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Queensland 4072, Australia.
- Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
MeSH Terms
- Animals
- Antigens, Viral / metabolism
- Central Nervous System / virology
- Disease Models, Animal
- Female
- Horse Diseases / pathology
- Horse Diseases / virology
- Horses / virology
- Humans
- Male
- Mice
- Organ Specificity
- Species Specificity
- Viral Nonstructural Proteins / immunology
- Viral Nonstructural Proteins / metabolism
- Virulence
- Virus Replication
- West Nile Fever / pathology
- West Nile Fever / veterinary
- West Nile Fever / virology
- West Nile virus / immunology
- West Nile virus / pathogenicity
- West Nile virus / physiology
Citations
This article has been cited 6 times.- Nett RJ, Brault AC, Lambert AJ, Agnihothram S, Barrett ADT, Barzon L, Clements DE, Durbin A, Kretschmer M, Monath TP, Mura M, Pierson TC, Prutzman K, Slifka MK, Suthar MS, Whitehead SS, Staples JE. Summary of human West Nile virus vaccine meeting, 2024: Investigating barriers to development. Vaccine 2025 Dec 5;68:127938.
- Visser I, Marshall EM, Agliani G, Rissmann M, van den Brand JMA, Koopmans MPG, Rockx B. In vitro and in vivo characterization of a novel West Nile virus lineage 2 strain. Npj Viruses 2024 Nov 25;2(1):61.
- Baric TJ, Reneer ZB. Animal Models, Therapeutics, and Vaccine Approaches to Emerging and Re-Emerging Flaviviruses. Viruses 2024 Dec 24;17(1).
- McGuckin Wuertz K, Treuting PM, Hemann EA, Esser-Nobis K, Snyder AG, Graham JB, Daniels BP, Wilkins C, Snyder JM, Voss KM, Oberst A, Lund J, Gale M Jr. STING is required for host defense against neuropathological West Nile virus infection. PLoS Pathog 2019 Aug;15(8):e1007899.
- Santos RI, Hermance ME, Gelman BB, Thangamani S. Spinal Cord Ventral Horns and Lymphoid Organ Involvement in Powassan Virus Infection in a Mouse Model. Viruses 2016 Aug 12;8(8).
- Prow NA, Edmonds JH, Williams DT, Setoh YX, Bielefeldt-Ohmann H, Suen WW, Hobson-Peters J, van den Hurk AF, Pyke AT, Hall-Mendelin S, Northill JA, Johansen CA, Warrilow D, Wang J, Kirkland PD, Doggett S, Andrade CC, Brault AC, Khromykh AA, Hall RA. Virulence and Evolution of West Nile Virus, Australia, 1960-2012. Emerg Infect Dis 2016 Aug;22(8):1353-62.
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