Genetic determinants modulating the pathogenic phenotype of tick-borne orbiviruses

Abstract

Genetic studies have been carried out on orbiviruses in the Great Island (GI) antigenic subgroup of the Kemerovo serogroup ( Orbivirus, 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 W 4G 6 (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, G 4W 5, 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.