GENETIC-MAPPING OF THE DETERMINANTS OF PLAQUE MORPHOLOGY OF COXSACKIEVIRUS B4

The genetic determinants of plaque size of two variants of coxsackievi rus B4, CB4-P and CB4-V, were identified using a panel of recombinant, chimeric viruses. When grown in monkey kidney cells, CB4-V yielded la rge plaques with an average size of 1.0 cm while CB4-P yielded small p laques with an average size of 0.4 cm. Two genetic domains, the 5' unt ranslated region and the VP4 gene sequence, independently influenced p laque size. Recombinant viruses containing the CB4-P genetic backgroun d with point mutations in either the VPI or VP2 coding sequences had s mall plaque phenotypes. However, two additional chimerics containing t he CB4-P genetic background with either a point mutation. in the VP4 s equence or four substitutions in the 5' untranslated region, had large plaque phenotypes. Plaque size correlated with growth kinetics under single-step conditions. Large-plaque variants replicated to higher tit ers than small-plaque variants. Comparison of the growth kinetics of t he recombinant viruses revealed some differences in viral replication. These data suggest that both the 5' untranslated region and arg-16 of VP4 influence viral replication but at different stages of the replic ation cycle.