Genetic determinants modulating the pathogenic phenotype of tick-borne orbiviruses.

Genetic studies have been carried out on orbiviruses in the Great Island (GI) antigenic subgroup of the Kemerovo serogroup (Orbivrus, Reoviridae) to elucidate the functions of the 10 genomic double-stranded RNA segments. Such studies have shown that segment 4 is the major genetic determinant of neurovirulence (P.A. Nuttall, S.R. Moss, L.D. Jones, and D. Carey, 1989, Virology 172, 428-434), whereas segment 5 of Wexford (WEX) virus and segment 6 of GI virus are the major determinants of serotype specificity (S.R. Moss, C.M. Ayres, and P.A. Nuttall, 1987, Virology 157, 137-144; S.R. Moss, C.M. Ayres, and P.A. Nuttall, 1988, J. Gen. Virol. 69, 2721-2727). In studies with reassortants isolated following dual infection of cell cultures with WEX and GI viruses, the gene combination W4G6 (i.e., viruses deriving segment 4 from WEX virus and segment 6 from GI virus) resulted in nonpathogenic reassortants. Unlike the parental viruses, the avirulent reassortants did not produce clinical evidence of infection in inoculated 2-day-old mice although, suprisingly, they replicated in the brains of the mice. The alternate heterotypic gene combination, G4W5, resulted in typical neurovirulent reassortants. The results indicate that segment 6 of GI virus is able to modulate the phenotypic expression of segment 4 of WEX virus, but not vice versa. Modulation probably results from interactions between the products of these two genomic segments, possibly at the level of virion structure.