RABIES VIRUS QUASI-SPECIES - IMPLICATIONS FOR PATHOGENESIS

Passage of the mouse-adapted rabies virus strain CVS-24 (where CVS is challenge virus standard) in BHK cells results in the rapid selection of a dominant variant designated CVS-B2c that differs genotypically an d phenotypically from the dominant variant CVS-N2c present in mouse-br ain- or neuroblastoma-cell-passaged CVS-24. The glycoprotein of CVS-B2 c has 10 amino acid substitutions compared with that of CVS-N2c, Becau se CVS-B2e can be reproducibly selected in BHK cells, it is likely to be a conserved minor subpopulation of CVS-24, CVS-N2c is more neurotro pic in vitro and in vivo than CVS-B2c, which replicates more readily i n nonneuronal cells in vitro and in vivo. These characteristics appear to be relevant to the pathogenicity of the two variants. CVS-N2c is m ore pathogenic for adult mice than CVS-B2c. In contrast, CVS-B2c is mo re pathogenic for neonatal mice. These differences in pathogenicity ar e reflected in the selection pattern when mixtures of CVS-N2c and CVS- B2c were used to infect neonatal and adult mice. Although CVS-N2c was highly selected in adult mice, no selection for either variant was see n in neonates, suggesting that certain aspects of development, such as maturation of the nervous and immune systems, may contribute to the s election process. We speculate that the existence of different variant s within a rabies virus strain may facilitate the virus in overcoming barriers to its spread, both within the host and between species.