Abstract
In recent decades, vaccination has substantially reduced the number of measles cases to levels close to the elimination stage. However, major measles outbreaks occurred in Europe during 2010–2012, after the introduction of the D4-Enfield lineage. We have performed a molecular characterization of 75 measles virus genotype D4 strains from patients infected in Spain between 2004 and 2012 by sequencing the N-450 region and the M-F non-coding region (M-F NCR) in order to identify genetic features of these viruses. The analysis of the N-450 region confirmed that all samples obtained since 2008 belonged to variants or sets of identical sequences of the D4-Enfield lineage, including a new one named MVs/Madrid.ESP/46.10/. Analysis of the M-F NCR showed insertions and deletions associated with previously described, uncommon non-standard genome length measles viruses. This genetic feature was identified in the D4-Enfield lineage viruses, but not in the other D4 viruses that were circulating in Spain before 2008, suggesting that these non-standard length M-F NCR sequences are characteristic of the D4-Enfield lineage. The results of the phylogenetic analysis of Spanish M-F NCRs suggest higher resolution in discriminating strains than did the N-450 analysis. In addition, the results of the analysis of the M-F NCR on the MVs/Madrid.ESP/46.10/ sub-lineage seem to support the potential utility of this region as a tool for epidemiological surveillance complementary to the N-450 region, as previously suggested. Further investigation on this question, as well as the surveillance of new potentially emerging strains with non-standard length M-F NCR are strongly recommended as part of future strategies for measles elimination.
Highlights
Measles is a highly contagious infectious disease caused by the measles virus (MeV), which continues to be a major cause of infant mortality throughout the world and of continuing outbreaks in developed countries, despite the existence of an effective live-attenuated vaccine.In the WHO European Region, vaccination substantially reduced the number of measles cases from the 1990s to 2009
After several years with a low incidence of measles cases, large outbreaks occurred in Europe between 2010 and 2012 after the introduction of the D4-Enfield lineage at the end of 2007, which replaced the previously circulating D4-Bucharest lineage viruses [1,2]
Among the factors that might have contributed to this widespread MeV dissemination could be the special features of the viruses themselves
Summary
Measles is a highly contagious infectious disease caused by the measles virus (MeV), which continues to be a major cause of infant mortality throughout the world and of continuing outbreaks in developed countries, despite the existence of an effective live-attenuated vaccine.In the WHO European Region, vaccination substantially reduced the number of measles cases from the 1990s to 2009. The MeV genome has a standard size of 15,894 nucleotides (nt), obeying the rule of six, that characterizes the morbilliviruses According to this rule, the total number of nucleotides comprising the MeV genome must be divisible by six for the virus to be viable. The M-F non-coding region (M-F NCR) of the MeV genome comprises a 426-nt 3’ UTR of the matrix protein gene (M 3’UTR), an intergenic region of 3 nt, and a 583-nt 5’ UTR of the fusion protein gene (F 5’UTR). This is the longest non-coding region of the MeV (1012 nt), and it is rich in G-C- with homopolymeric sequences [5, 6]. The M-F NCR region is one of the most variable regions of the MeV genome [6, 10] and has recently been proposed as a new target for MeV molecular characterization [11]
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