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Streamlined Whole-Genome Sequencing of Mumps Virus for High-Resolution Outbreak Analysis
Patrick Bryant1, Haley Caldwell1, Daryl M Lamson1
1Laboratory of Viral Diseases, Wadsworth Centergrid.465543.5, New York State Department of Health, Albany, New York, USA.
Abstract:
Since 2015, the United States has experienced a resurgence in the number of mumps cases and outbreaks in fully vaccinated populations. These outbreaks have occurred predominantly in close-quarter settings, such as camps, colleges, and detention centers. Phylogenetic analysis of 758 mumps-positive samples from outbreaks across the United States identified 743 (98%) as genotype G based on sequence analysis of the mumps small hydrophobic (SH) gene. Additionally, SH sequences in the genotype G samples showed almost no sequence diversity, with 675 (91%) of them having identical sequences or only one nucleotide difference. This uniformity of circulating genotype and strain created complications for epidemiologic investigations and necessitated the development of a system for rapidly generating mumps whole-genome sequences for more detailed analysis. In this study, we report a novel and streamlined assay for whole-genome sequencing (WGS) of mumps virus genotype G. The WGS procedure successfully generated 318 high-quality WGS sequences on nucleic acid from genotype G-positive respiratory samples collected during several mumps outbreaks in the United States between 2016 and 2019. Sequencing was performed by a rapid and highly sensitive custom Ion AmpliSeq mumps genotype G panel, with sample preparation performed on an Ion Chef and sequencing on an Ion S5. The WGS data generated by the AmpliSeq panel provided enhanced genomic resolution for epidemiological outbreak investigations. Translation and protein sequence analysis also identified several potentially important epitope changes in the circulating mumps genotype G strains compared to the Jeryl-Lynn strain (JL5) used in vaccines in the United States, which could explain the current level of vaccine escapes.
Insights
Mumps outbreaks in vaccinated populations are linked to a uniform genotype G strain. A new whole-genome sequencing method provides detailed analysis and reveals potential vaccine escape mechanisms.
Area of Science:
- Virology
- Epidemiology
- Genomics
Background:
- Resurgence of mumps cases and outbreaks in fully vaccinated populations in the US since 2015.
- Outbreaks predominantly occurred in close-quarter settings.
- Phylogenetic analysis identified genotype G as the predominant mumps strain (98%) with minimal sequence diversity.
Purpose of the Study:
- To develop a rapid and streamlined assay for whole-genome sequencing (WGS) of mumps virus genotype G.
- To enhance genomic resolution for epidemiological investigations of mumps outbreaks.
Main Methods:
- Development of a custom Ion AmpliSeq mumps genotype G panel for rapid WGS.
- Sample preparation using Ion Chef and sequencing on Ion S5.
- Analysis of nucleic acid from genotype G-positive respiratory samples.
Main Results:
- Successfully generated 318 high-quality WGS sequences from mumps genotype G outbreaks (2016-2019).
- WGS data provided enhanced genomic resolution for outbreak investigations.
- Identified potential epitope changes in circulating strains compared to the Jeryl-Lynn vaccine strain.
Conclusions:
- The novel WGS assay is effective for characterizing mumps genotype G.
- Identified epitope changes may explain current vaccine escape phenomena.
- Genomic surveillance is crucial for understanding and controlling mumps outbreaks.
