title: Development of a mouse model system, coding assignments and identification of the genome segments controlling virulence of African horse sickness virus serotypes 3 and 8.
abstract: Attenuated (att) and wild type (wt) strains of the nine AHSV serotypes were evaluated for virulence in adult Balb C mice. Although most were avirulent in this system, isolates of AHSV 1att, 3wt, 3att, 4wt, 5att, 7att and 8att caused some mortality when administered via an intranasal route. After plaque cloning, only the attenuated vaccine strain of AHSV 7att caused any mortality via an intravenous route. AHSV 3att and AHSV 8wt were virulent (V) and avirulent (AV) (respectively) in the mouse model and were selected as parental strains for production of genome segment reassortants. These progeny virus strains were plaque cloned, then characterised to identify the genome segments that influence virulence of AHSV in the mouse model. Three virulence phenotypes were observed: fully virulent (V); fully avirulent (A); and a novel intermediate virulence (N) not expressed by either parental strain. Genome segment 2 (encoding outer capsid protein VP2) from the avirulent parent appeared to have a controlling influence in production of the A phenotype. Reassortants with the V phenotype all contained segment 2 from the virulent parent, however in each case they also contained genome segments 5 and 10, also from AHSV 3 (V). Genome segments 5 and 10 encode the smaller outer capsid protein VP5 and the non structural proteins NS3/NS3a, respectively. A combination of genome segments 2, 5 and 6 from the avirulent parent and segment 10 from the virulent parent were found in each of the virus strains with the N phenotype. However, comparison of two reassortants (A79 and A790), which differ only in a single segment, showed that replacement of genome segment 10 from the avirulent parent with that from the virulent parent, conferred the N phenotype on A790.
authors.affiliation: Institute for Animal Health, Pirbright Laboratory, Woking, U.K.
authors.forename: R S
authors.initials: RS
authors.lastname: O'Hara
authors.forename: A J
authors.initials: AJ
authors.lastname: Meyer
authors.forename: J N
authors.initials: JN
authors.lastname: Burroughs
authors.forename: L
authors.initials: L
authors.lastname: Pullen
authors.forename: L A
authors.initials: LA
authors.lastname: Martin
authors.forename: P P
authors.initials: PP
authors.lastname: Mertens
mesh_terms: D000355:African Horse Sickness / Q000401:mortality / Q000821:virology*; D000356:African Horse Sickness Virus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D016679:Genome, Viral; D006736:Horses; D051379:Mice; D008807:Mice, Inbred BALB C; D012330:RNA, Double-Stranded / Q000032:analysis / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D011817:Rabbits; D012692:Serial Passage; D012703:Serotyping; D014613:Vaccines, Attenuated; D014764:Viral Proteins / Q000235:genetics; D014765:Viral Vaccines; D014774:Virulence / Q000235:genetics
chemical_list: D012330:RNA, Double-Stranded; D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D014765:Viral Vaccines