Replication of coxsackievirus B3 in primary cell cultures generates novel viral genome deletions

Coxsackievirus B3 (CVB3) generates 5′-terminally deleted genomes (TDs) during replication in murine hearts. We show here that CVB3 populations with TDs can also be generated within two to three passages of CVB3 in primary, but not immortalized, cell cultures. Deletions of less than 49 nucleotides increase in size during passage, while 5′ TDs of 49 nucleotides appear to be the maximum deletion size. The cellular environment of contact-inhibited primary cell cultures or the myocardium in vivo is sufficient for the selection of 5′ TDs over undeleted genomes.