Revealing New Measles Virus Transmission Routes by Use of Sequence Analysis of Phosphoprotein and Hemagglutinin Genes

Abstract

With improved measles virus (MV) control, the genetic variability of the MV-nucleoprotein hypervariable region (NP-HVR) decreases. Thus, it becomes increasingly difficult to determine the origin of a virus using only this part of the genome. During outbreaks in Europe and Africa, we found MV strains with identical NP-HVR sequences. However, these strains showed considerable diversity within a larger sequencing window based on concatenated MV phosphoprotein and hemagglutinin genes (P/H pseudogenes). In Belarus, Germany, Russia, and the Democratic Republic of Congo, the P/H pseudogenes provided insights into chains of transmission, whereas identical NP-HVR provided none. In Russia, for instance, the P/H pseudogene identified temporal clusters rather than geographical clusters, demonstrating the circulation and importation of independent variants rather than large local outbreaks lasting for several years, as suggested by NP-HVR. Thus, by extending the sequencing window for molecular epidemiology, a more refined picture of MV circulation was obtained with more clearly defined links between outbreaks and transmission chains. Our results also suggested that in contrast to the P gene, the H gene acquired fixed substitutions that continued to be found in subsequent outbreaks, possibly with consequences for its antigenicity. Thus, a longer sequencing window has true benefits both for the epidemiological surveillance of measles and for the better monitoring of viral evolution.

Perspective on Global Measles Epidemiology and Control and the Role of Novel Vaccination Strategies

“…Genotypic surveillance of MeV is based on the nucleotide sequence encoding the 150 carboxyl-terminal amino acids of the N protein (N450), a region of high variability in the genome [ 61 ]. This method effectively differentiates between the 24 MeV genotypes, six of which (B3, D4, D8, D9, G3, and H1) currently remain in circulation worldwide [ 41 , 44 , 62 , 63 ]. At this writing, more than 33,210 sequences of MeV have been submitted from all WHO regions to the global Measles Nucleotide Surveillance (MeaNS) database [ 62 ].…”

Wild-Type Measles Viruses with Non-Standard Genome Lengths

“…All vaccine strains belong to genotype A. However, N-450 does not always provide sufficient resolution to differentiate lineages within one genotype [19] . Differentiation of co-circulating lineages within a genotype may require expansion of the size of the region of the genome used for sequence analysis.…”

Molecular Characterization of Wild Type Measles Virus from Adult Patients in Northern China, 2014

“…39 Mutations in the H gene are likely to become fixed in the viral genome and form distinct clusters. 40 In this study, we showed that the H protein of all the wild type viruses carried S240N substitutions resulting in the deletion of the putative N-linked glycosylation site at amino acid 238. Our data were consistent with previous reports showing the absence of this glycosylation site in all circulating H1 cluster1 strains in 2000-2009.…”