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Abstract
The length of the single stranded, negative sense RNA genome of measles virus (MeV) is highly conserved at 15,894 nucleotides (nt). MeVs can be grouped into 24 genotypes based on the highly variable 450 nucleotides coding for the carboxyl-terminus of the nucleocapsid protein (N-450). Here, we report the genomic sequences of 2 wild-type viral isolates of genotype D4 with genome lengths of 15,900 nt. Both genomes had a 7 nt insertion in the 3′ untranslated region (UTR) of the matrix (M) gene and a 1 nt deletion in the 5′ UTR of the fusion (F) gene. The net gain of 6 nt complies with the rule-of-six required for replication competency of the genomes of morbilliviruses. The insertions and deletion (indels) were confirmed in a patient sample that was the source of one of the viral isolates. The positions of the indels were identical in both viral isolates, even though epidemiological data and the 3 nt differences in N-450 between the two genomes suggested that the viruses represented separate chains of transmission. Identical indels were found in the M-F intergenic regions of 14 additional genotype D4 viral isolates that were imported into the US during 2007–2010. Viral isolates with and without indels produced plaques of similar size and replicated efficiently in A549/hSLAM and Vero/hSLAM cells. This is the first report of wild-type MeVs with genome lengths other than 15,894 nt and demonstrates that the length of the M-F UTR of wild-type MeVs is flexible.
Highlights
Measles virus (MeV) is a member of the genus Morbillivirus in the family Paramyxoviridae
Phylogenetic analysis based on N-450 determined that the genotype of both viral isolates was D4
The indels were found in minimally passaged viral isolates and their presence was confirmed in the patient specimens
Summary
Measles virus (MeV) is a member of the genus Morbillivirus in the family Paramyxoviridae. Its non-segmented, negative sense RNA genome contains six genes separated by conserved intergenic trinucleotides [1]. The coding regions are preceded and followed by untranslated regions (UTRs) (Fig. 1a), which include conserved transcription start and stop sequences, leading to the transcription of monocistronic mRNAs. Highly conserved promoter and encapsidation signals are located in the 52 nucleotide (nt) leader sequence and 37 nt trailer sequence at the termini of the genome. The 1012 nt M-F UTR is highly variable and GC-rich, containing many homopolymeric sequences [1,2,3,4]. Experiments with plasmid-based transcription assays and recombinant MeVs indicated that the MF UTR modulates the production of the M and F proteins [5,6,7,8]. The F protein, consisting of subunits F1 and F2 is required for fusion of the virion with the host cell [9]
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