Nucleotide sequences and mutations of the 5 '-nontranslated region (5 ' NTR) of natural isolates of an epidemic echovirus 11 ' (prime)

An echovirus 11' (prime) virus caused an epidemic in Hungary in 1989. The l eading clinical form of the diseases was myocarditis. Hemorrhagic hepatitis syndroms were also caused, however, with lethal outcome in 13 newborn babi es. Altogether 386 children suffered from registered clinical disease. No a ccumulation of serous meningitis cases and intrauterine death were observed during the epidemic, and the monovalent oral poliovirus vaccination campai gn has prevented the further circulation of the virus. The 5'-nontranslated region (5'-NTR) of 12 natural isolates were sequenced (nucleotides: 260-577). The 5'-NTR was found to be different from that of t he prototype Gregory strain (X80059) of EV11 (less than 90% identity), but related to the swine vesicular disease virus (D16364) SVDV and EV9 (X92886) as indicated by the best fitting dendogram. The examination of the variabl e nucleotides in the internal ribosomal entry site (IRES) revealed, that th e nucleotide sequence of a region of the epidemic 5'-NTR was identical to t hat of coxsackievirus B2. Five of the epidemic isolates were found to carry mutations. Seven EV11' IRES elements possessed identical sequences indicat ing, that the virus has evolved before its arrival to Hungary. The comparat ive examination of the suboptimal secondary structures revealed, that no on e of the mutations affected the secondary structure of stem-loop structures IV and V in the IRES elements. Although it has been shown previously, that the echovirus group is genetically coherent and related to coxsackie B vir uses the sequence differences in the epidemic isolates resulted in profound modification of the central stem (residues 477-529) of stem-loop structure No.V known to be affecting neurovirulence of polioviruses. Two alternate c loverleaf (stem-loop) structures were also recognised (nucleotides 376 to 4 60 and 540 to 565) which seem to mask both regions of the IRES element comp lementary to the 3'-end of the 18 S rRNA (460 to 466 and 561 to 570), thus probably diminishing initiation of translation. The possible biological imp ortance of the alternative cloverleaf structures is supported by the fact t hat neither the 17 variable nucleotides nor the two mutations of epidemic i solates within the regions seem to modify the predicted alternative seconda ry structures in EV11, SVDV and CBV1-4.