CARDIOVIRAL POLY(C) TRACTS AND VIRAL PATHOGENESIS

Mengovirus is a prototypical member of the cardiovirus genus of the fa mily Picornaviridae. The positive-strand RNA genome is 7761 bases in l ength and encodes a polyprotein of 2293 amino acids. The 5' non-coding region (758 bases) contains an unusual homopolymeric poly(C) tract, W hich in the wild-type virus, has a sequence of C50UC10. We have discov ered through genetic engineering that truncation or deletion of this p oly(C) sequence yields infectious virus isolates that grow well in cel l culture, but are 10(6) to 10(9) fold less pathogenic to mice than th e wild type strain. Animals receiving sublethal doses of the short pol y(C) strains characteristically develop high levels of neutralizing an tibodies and acquire lifelong protective immunity against challenge wi th wild type virus. Effectively, the genetically engineered strains ar e superb vaccines against cardiovirus disease. Moreover, their potenti al is not limited to murine hosts. Pigs and sub-human primates have al so been protectively vaccinated with short poly(C) tract Mengoviruses. The molecular mechanism of poly(C)-mediated pathogenesis is currently under study. Most hypotheses link the activity to induction of the an tiviral cytokine, interferon.