Biochemistry and pathogenicity of echovirus 9. III. Thermosensitive mutants of echovirus 9, strain Barty, with reduced pathogenicity for newborn mice.

Different clinical isolates of echovirus 9 are known to vary strikingly with regard to pathogenicity. Prototype strain Hill and strain Barty have previously been shown to differ not only in paralytogenic potency for newborn mice but also in a number of in vitro characteristics related to virus capsid structures. A series of mutants of strain Barty, thermosensitive for replication at 40 degrees C, was isolated after mutagenization with 5-fluorouracil. For all mutants the virus dose required to paralyze 50% of the infected animals was significantly higher than of the parent strain Barty. This reduced pathogenicity was observed at normal room temperature where the baby mice had a body temperature of 32.5 degrees C, which is even below the permissive temperature for growth of the mutants. The paralytogenic potencies did not further decrease when the mice where kept at elevated room temperature and had a body temperature of 35.1 degrees C. Thus, the reduced pathogenicity is apparently not a direct consequence of thermosensitivity of growth. Biochemical and biophysical characterization indicated that at least two of the eight mutants have an alteration in capsid protein.