GENERATION OF AN INFECTIOUS CDNA OF A HIGHLY CARDIOVIRULENT COXSACKIEVIRUS B3(CVB3(M)) AND COMPARISON TO OTHER INFECTIOUS CVB3 CDNAS

An infectious cDNA of a highly myocarditic coxsackievirus B3 (CVB3(m); Nancy strain) was cloned. Sequence data revealed 43 extra non-viral n ucleotides upstream of the initial 5' sequence. However, the authentic 5' end sequence was maintained during replication of viral RNA transf ected into HeLa cells, suggesting the RNA synthesizing complex edits t he picornaviral 5' terminus sequence. Nucleotide sequences of the 5' n ontranslated region and the capsid protein gene sequence of CVB3(m) we re compared with the published sequences of five other CVB3 Nancy stra ins and two main lineages were found. In comparative assays for cardio virulence, three of four CVB3 tested were cardiovirulent in adolescent male CD-1 mice. Only one of the three available CVB3 strains was neut ralized with several anti-CVB3(m) monoclonal antibodies, suggesting th at mutations in the surface epitopes of the capsid polypeptides contri bute to antigenic drift within the serotype, perhaps in part through i mmunoselective pressures. Thus, phenotypic diversity of CVB3 within th e prototype Nancy strain is an example of RNA viruses adapting to chan ging environments (cells, mice and humans) through mutations and selec tive pressure. (C) 1997 Elsevier Science B.V.