Whole-genome analysis of mumps virus genotype F in Shandong, China (2006-2018).

Introduction: Despite the introduction of mumps-containing vaccines into the routine immunization program in 2008, mumps incidence in Shandong Province, China, declined but remained substantially higher than that of measles and rubella, and above WHO elimination thresholds, raising the possibility of whether genetic evolution of circulating strains has contributed to this phenomenon. To address, we compared mumps viruses isolated pre-vaccine (2006-2007) and a decade after rollout (2018). Methods: We analyzed mumps case data reported in Shandong from 2005 to 2024. We also performed whole-genome sequencing on 16 mumps virus strains isolated during the same period. Phylogenetic analyses were conducted to characterize viral genetic features and identify mutations. Results: From 2005 to 2024, 167,590 mumps cases were reported, peaking in 2012 (25.33 per 100,000 population). SH-gene typing consistently identified all 16 strains as genotype F, a result corroborated by whole-genome phylogeny; however, the SH gene alone proved insufficient for phylogenetic resolution among closely related strains, consistent with the value of whole-genome sequencing for epidemiological surveillance. The 16 full-length genomes shared 98.34-100% nucleotide identity. Phylogenetic analysis revealed intermingling of 2006-2007 and 2018 isolates rather than time-specific clustering, with low inter-group p-distances. Importantly, between the two temporal groups, no significant differences were detected in their respective identities to the vaccine strain S79 at the whole-genome level (nucleotide or amino acid). Two positively selected sites were identified across the seven structural proteins (posterior probability > 0.95). Eight mutations in HN and F that alter hydrophilicity, hydrophobicity, or charge were found, but structural modeling predicted no appreciable conformational changes. Conclusion: We provides a whole-genome-based, two-time point comparison of genotype F mumps viruses in Shandong across a ~ 12-year interval spanning vaccine introduction (2006-2007 vs. 2018). Overall, the Shandong 2018 isolates remained as similar to the 2006-2007 isolates as F strains are nationwide, and both groups were comparably close to vaccine strain S79, indicating no detectable genetic divergence or drift over the ~12-year period. As the SH gene alone lacked sufficient diversity to resolve closely related isolates, whole-genome sequencing provided more accurate genetic characterization in this study.