Suen, W.W.Prow, N.A.Setoh, Y.X.Hall, R.A.Bielefeldt Ohmann, H.2025-12-182025-12-182016Journal of General Virology, 2016; 97(2):366-3770022-13171465-2099https://hdl.handle.net/11541.2/137908Data source: Supplementary Material, https://doi.org/10.1099/jgv.0.000356Viruses of intermediate virulence are defined as isolates causing an intermediate morbidity/mortality rate in a specific animal model system, involving specific host and inoculation parameters (e.g. dose and route). Therefore, variable disease phenotype may exist between animals that develop severe disease or die and those that are asymptomatic or survive after infection with these isolates. There may also be variability amongst animals within each of these subsets. Such potential variability may confound the use of time-point sacrifice experiments to investigate pathogenesis of this subset of virus strains, as uniformity in disease outcome is a fundamental assumption for time-course sacrifice experiments. In the current study, we examined the disease phenotype, neuropathology, neural infection and glial cell activity in moribund/dead and surviving Swiss white (CD-1) mice after intraperitoneal infection with various Australian flaviviruses, including West Nile virus (WNV) strains of intermediate virulence (WNV NSW2011 and WNV NSW2012 ), and highly virulent Murray Valley encephalitis virus (MVEV) isolates. We identified notable intragroup variation in the end-point disease in mice infected with either WNV NSW strain, but to a lesser extent in mice infected with MVEV strains. The variable outcomes associated with WNV NSW infection suggest that pathogenesis investigations using time-point sacrifice of WNV NSW -infected mice may not be the best approach, as the assumption of uniformity in outcomes is violated. Our study has therefore highlighted a previously unacknowledged challenge to investigating pathogenesis of virus isolates of intermediate virulence. We have also set a precedent for routine examination of the disease phenotype in moribund/dead and surviving mice during survival challenge experiments.enCopyright 2016 The Authors. This article is open access and allows authors and their funding bodies to make published articles freely available online from the time of publication, upon payment of an Article Processing Charge (APC) (https://jgv.microbiologyresearch.org/about/open-access-policy)Journal article10.1099/jgv.0.0003562-s2.0-84959174944