Genetic characterization on the nucleoprotein and fusion gene of wild-type measles virus circulating in Shanghai, 2001–2022

Measles is an acute and highly contagious viral disease that poses significant public health challenges globally. Since 2001, continuous virologic surveillance has been conducted in Shanghai, enabling a comprehensive analysis of the evolution of the nucleoprotein (N gene) and fusion gene (F gene) of the measles virus (MeV) over a 21-year period. Between 2001 and 2022, there were a total of 1405 MeV strains isolated by the Shanghai Center for Disease Control and prevention (SCDC), including 6 strains of genotype D8, 8 strains of genotype B3, 12 strains of genotype H1b, and the remaining strains of genotype H1a. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the 3' end of the N gene (450 nt) and the complete sequence of the F gene (1622 nt) from the viral isolates. Sequencing of the RT-PCR products was followed by nucleotide and amino acid phylogenetic analyses. The substitution rates were for the F and N genes in Shanghai were determined to be 0.89 × 10^-3 and 2.20 × 10^-3 substitutions site^/year, respectively. Globally, the nucleotide and amino acid similarities of the N gene among 13,498 MeV isolates ranged from 89.1 %-100.0 % and 90.2 %-100.0 %, respectively. Notably, the F gene exhibited 16 high-amino-acid-mutation sites, most of which differed among H1a MeV strains compared to the Shanghai-191 vaccine strain. The deletion of the glycosylation site at aa 9-11(NVS) was primarily observed in H1a and H1b of MeV strains. However, critical functional sites in the F gene remained conserved. In conclusion, the previously predominant indigenous H1a wild-type measles virus (MeV) has not been detected for over two years, with only imported MeV genotypes currently being identified. It is crucial to strengthen the surveillance of MeV genotypes to facilitate the timely identification and containment of imported measles cases, thereby preventing potential outbreaks.