5′ terminal deletions in the genome of a coxsackievirus B2 strain occurred naturally in human heart

Enteroviruses can induce human myocarditis, which can be modeled in mice inoculated with group B coxsackieviruses (CVB) and in which CVB evolve to produce defective, terminally deleted genomes. The 5′ non-translated region (NTR) was enzymatically amplified from heart tissue of a fatal case of enterovirus-associated myocarditis in Japan in 2002. While no intact 5′ viral genomic termini were detected, 5′ terminal deletions ranged in size from 22 to 36 nucleotides. Sequence of the 5′ third of this viral genome is of a modern strain, closely related to CVB2 strains isolated in Japan in 2002. A CVB3 chimera containing the 5′ NTR with a 22 nt deletion produced progeny virus upon transfection of HeLa cells. When the 5′ 22 nucleotide deletion was repaired, the virus induced myocarditis in mice and replicated like wild type virus in murine heart cells. This is the first report of these naturally-occurring defective enteroviral genomes in human myocarditis.