title: Pathogenicity study in sheep using reverse-genetics-based reassortant bluetongue viruses.
abstract: Bluetongue (BT) disease, caused by the non-enveloped bluetongue virus (BTV) belonging to the Reoviridae family, is an economically important disease that affects a wide range of wild and domestic ruminants. Currently, 26 different serotypes of BTV are recognized in the world, of which BTV-8 has been found to exhibit one of the most virulent manifestations of BT disease in livestock. In recent years incursions of BTV-8 in Europe have resulted in significant morbidity and mortality not only in sheep but also in cattle. The molecular and genetic basis of BTV-8 pathogenesis is not known. To understand the genetic basis of BTV-8 pathogenicity, we generated reassortant viruses by replacing the 3 most variable genes, S2, S6 and S10 of a recent isolate of BTV-8, in different combinations into the backbone of an attenuated strain of BTV-1. The growth profiles of these reassortant viruses were then analyzed in two different ovine cell lines derived from different organs, kidney and thymus. Distinct patterns for each reassortant virus in these two cell lines were observed. To determine the pathogenicity of these reassortant viruses, groups of BTV-susceptible sheep were infected with each of these viruses. The data suggested that the clinical manifestations of these two different serotypes, BTV-1 and BTV-8, were slightly distinct and BTV-1, when comprising all 3 genome segments of BTV-8, behaved differently to BTV-1. Our results also suggested that the molecular basis of BT disease is highly complex.
authors.affiliation: Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Celma
authors.affiliation: Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: Bishnupriya
authors.initials: B
authors.lastname: Bhattacharya
authors.affiliation: Institut für Virusdiagnostik, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. Electronic address: michael.eschbaumer@ars.usda.gov.
authors.forename: Michael
authors.initials: M
authors.lastname: Eschbaumer
authors.affiliation: Institut für Virusdiagnostik, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wernike
authors.affiliation: Institut für Virusdiagnostik, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Beer
authors.affiliation: Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom. Electronic address: polly.roy@lshtm.ac.uk.
authors.forename: Polly
authors.initials: P
authors.lastname: Roy
mesh_terms: D000818:Animals; D001819:Bluetongue / Q000821:virology*; D001820:Bluetongue virus / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D016865:Reassortant Viruses / Q000235:genetics / Q000472:pathogenicity*; D059386:Reverse Genetics / Q000379:methods / Q000662:veterinary*; D065288:Serogroup; D012756:Sheep; D019562:Viral Load / Q000662:veterinary; D014774:Virulence / Q000235:genetics
keywords: Bluetongue virus; Non-structural protein NS3; Pathogenicity in sheep; Reassortment; Serotype 8