Evaluation of a mouse model for the West Nile virus group for the purpose of determining viral pathotypes

• DOI: 10.1099/vir.0.063537-0
• Publication Date: 2014-04-03T05:02:32Z
• Authors: John Bingham; Jean Payne; Jennifer Harper; Leah Frazer; Sarah Eastwood; Susanne Wilson; Sue Lowther; Ross Lunt; Simone Warner; Mary Carr; Roy A. Hall; Peter A. Durr
• Keywords: Central Nervous System; Male; 0301 basic medicine; Virulence; Pathotypes; Viral Nonstructural Proteins; Virus Replication; 630; Mouse model; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Species Specificity; Organ Specificity; 2406 Virology; Animals; Humans; Female; Horse Diseases; Horses; Antigens, Viral; West Nile virus; West Nile Fever

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.