Evaluation of a mouse model for the West Nile virus group for the purpose of determining viral pathotypes.
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.
Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
John
J
Bingham
Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
Jean
J
Payne
Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
Jennifer
J
Harper
Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
Leah
L
Frazer
Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
Sarah
S
Eastwood
Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
Susanne
S
Wilson
Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
Sue
S
Lowther
Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
Ross
R
Lunt
Biosciences Research Division, Department of Environment and Primary Industries Victoria, AgriBio Centre, 5 Ring Road, La Trobe University Campus, Bundoora, Victoria 3083, Australia.
Simone
S
Warner
Biosecurity SA, Primary Industries and Regions South Australia, GPO Box 1671, Adelaide, South Australia 5001, Australia.
Mary
M
Carr
Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Queensland 4072, Australia.
Roy A
RA
Hall
Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, Geelong, Victoria 3220, Australia.
Peter A
PA
Durr
D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D002490:Central Nervous System / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D006734:Horse Diseases / Q000473:pathology / Q000821:virology; D006736:Horses / Q000821:virology; D006801:Humans; D008297:Male; D051379:Mice; D009928:Organ Specificity; D013045:Species Specificity; D017361:Viral Nonstructural Proteins / Q000276:immunology / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication; D014901:West Nile Fever / Q000473:pathology / Q000662:veterinary / Q000821:virology*; D014902:West Nile virus / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology
D000956:Antigens, Viral; D017361:Viral Nonstructural Proteins; C531936:nonstructural protein 1, West Nile virus