MUTATIONAL ANALYSIS OF THE MENGOVIRUS POLY(C) TRACT AND SURROUNDING HETEROPOLYMERIC SEQUENCES

Previously, we described three mengovirus mutants derived from cDNA pl asmids, containing shortened poly(C) tracts (C-8, C-12, and C13UC10), that exhibited strong attenuation for virulence in mice yet grew like wild-type virus in HeLa cells. Thirteen additional mutants have now be en constructed and characterized. Five of these differ only in poly(C) length, including one with a precise deletion of the tract. The other mutants bear deletions into the regions juxtaposing poly(C). Studies with HeLa cells confirm the essential dispensability of mengovirus's p oly(C) tract but reveal a subtle, measurable correlation between poly( C) length and plaque diameter. Virulence studies with mice also reveal a strong correlation between poly(C) length and virulence. For the po ly(C)-flanking mutations, the 15 bases directly 5' of the tract proved dispensable for virus viability, whereas the 20 to 30 bases 3' of pol y(C) were critical for growth, thus implicating this region in the bas al replication of the virus.