Refined experimental design may increase the value of murine models for estimation of bluetongue virus virulence

Stokstad, Maria, Coetzee, Peter, Myrmel, Mette, Mutowembwa, Paidamwoyo, Venter, Estelle H., and Larsen, Stig (2021) Refined experimental design may increase the value of murine models for estimation of bluetongue virus virulence. Laboratory Animals, 55 (1). pp. 53-64.

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Abstract

Bluetongue is a serious non-contagious vector-borne viral disease in ruminants, causing poor animal welfare and economic consequences globally. Concern has been raised about the development of novel bluetongue virus (BTV) strains and their possibly altered virulence through the process of viral reassortment. Virulence is traditionally estimated in lethal dose 50 (LD50) studies in murine models, but agreement with bothin vitroand virulence in ruminants is questionable, and a refined experimental design is needed. Specific reassortants between wild-type and vaccine strains of BTV-1, -6 and -8 have previously been developed by reverse genetics. The aim of the present study was to rank thein vivovirulence of these parental and reassortant BTV strains by calculating LD(50)in a murine model by using an experimental design that is new to virology: a between-patient optimised three-level response surface pathway design. The inoculation procedure was intracranial. Fifteen suckling mice were used to establish LD(50)for each strain. Three parental and five reassortant virus strains were included. The LD(50)s varied from of 0.1 (95% confidence interval (CI) 0-0.20) to 3.3 (95% CI 2.96-3.72) tissue culture infectious dose 50/ml. The results support the hypothesis that reassortment in BTV may lead to increased virulence in mice with potential negative consequences for the natural ruminant host. The ranking showed low agreement within vitroproperties and virulence in ruminants according to existing literature. Refined design such as response surface pathway design was found suitable for use in virology, and it introduces significant ethical and scientific improvements.

Item ID: 63849
Item Type: Article (Research - C1)
ISSN: 1758-1117
Keywords: 3R, reduction, refinement LD50, reassortants, response surface pathway design, BTV
Copyright Information: (C)The Author(s) 2020
Funders: Norwegian University of Life Sciences, Animalia, South African National Research Foundation, University of Pretoria
Date Deposited: 22 Jul 2020 07:40
FoR Codes: 30 AGRICULTURAL, VETERINARY AND FOOD SCIENCES > 3009 Veterinary sciences > 300914 Veterinary virology @ 100%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280101 Expanding knowledge in the agricultural, food and veterinary sciences @ 100%
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