Molecular Epidemiology of B3 and D8 Measles Viruses through Hemagglutinin Phylogenetic History

Abstract

Of the 24 known measles genotypes, only D8 and B3 are responsible for outbreaks in the last years in Europe, Asia, and America. In this study the H gene of 92 strains circulating between 2015 and 2019 in Lombardy, Northern Italy, and 1273 H sequences available in GenBank were analyzed in order to evaluate the genetic variability and to assess the conservation of the immunodominant sites. Overall, in Lombardy we observed the presence of four different B3 and three different D8 clusters, each one of them including sequences derived from viruses found in both vaccinated and unvaccinated subjects. Worldwide, the residue 400 within the H protein, a position located within the main immune epitope, is mutated in all circulating strains that belong to the two globally endemic genotypes, B3 and D8. Our data demonstrate the usefulness of measles virus (MV) H gene sequencing. Indeed, the monitoring the H protein epitopes of circulating strains could be included in the measles laboratory surveillance activities in order to improve and optimize strategies for measles control, as countries go towards elimination phase.

Genetic Characterizations and Molecular Evolution of the Measles Virus Genotype B3’s Hemagglutinin (H) Gene in the Elimination Era

“…The collection time also revealed that these three clades circulated almost alternately, and that the sub-genotype 3.2/400V clade was the only variant circulating globally in the past decade. Similar results were also observed by Bianchi et al [19]. In a comparison of neutralizing antibody titers against outbreakassociated measles genotypes (D4, H1, and B3) in Iran, the lowest geometric mean titer of antibodies against B3 was observed [35].…”

“…The 2.5% and 2.0% nucleotide divergences in the MeV N and H genes, respectively, were used to define a new MeV genotype by the WHO criteria [30]. In this study, the results of phylogenetic analysis revealed two main sub-genotypes (3.1 and 3.2) of MeV B3's H gene, as reported previously [19,31,32], and the minimum genetic distance between the proposed B3 sub-genotypes (1.51%) did not match the 2.0% diversity threshold for assigning a new genotype. Based on the N450 gene, MeV B3 can be divided into three lineages [33,34].…”

“…A clade (400V) has also been identified [19]. Selection pressure analyses performed on all genotypes identified only a few sites under positive selection, and there is partial concordance between the studies (particularly sites 476 and 575) [18,19]. Here, we retrieved all complete sequences of B3's H gene from GenBank, and further confirmed and updated previous results.…”

“…In fact, 173 of the 174 sequences with a 471E, 172 of the 173 sequences with a 240N, and all of the sequences with a 283G or 303D belonged to sub-genotype 3.2. Another three substitutions (400V, 178T, and 307I) were found to be related to B3-400V clade branches, which were previously described in [19], and separated sub-genotype 3.2 into non-400V strains (collected from 1997 to 2012) and the 400V clade (collected from 2006 to 2019). The p-distance of nucleotides within these two groups was 0.89% ± 0.09% and 0.47% ± 0.08%, respectively.…”

“…There is a spatial and temporal difference between strains across subgenotypes and clades, and three mutations (positions 178, 307, and 400) were important in the evolution of sub-genotype 3.2. A clade (400V) has also been identified [19]. Selection pressure analyses performed on all genotypes identified only a few sites under positive selection, and there is partial concordance between the studies (particularly sites 476 and 575) [18,19].…”