Global mpox lineage discovery and rapid outbreak tracking with nanopore sequencing

Area of Science:

• Genomics
• Virology
• Epidemiology

Background:

• The 2022 human monkeypox virus 1 (hMPXV1) outbreak highlighted challenges in tracking viral spread and lineage emergence.
• Rapid accumulation of hMPXV1 mutations raised concerns about undetected variants with altered pathogenicity.
• Effective epidemiological studies and public health responses require accessible and standardized whole genome sequencing methodologies.

Purpose of the Study:

• To develop a rapid, accessible nanopore whole genome sequencing method for hMPXV1.
• To analyze hMPXV1 genomes from the Midwestern United States during the early outbreak.
• To establish a blueprint for deploying nanopore sequencing in genomic surveillance.

Main Methods:

• Development of a complete nanopore sequencing workflow, from DNA extraction to phylogenetic analysis.
• Sequencing of 84 complete hMPXV1 genomes from Illinois.
• Phylogenetic analysis to identify lineages and mutational profiles.

Main Results:

• A five-fold increase in available hMPXV1 genomes from the region was achieved.
• Two previously unnamed global hMPXV1 lineages were identified.
• Multiple introductions into the region and potential emergence of new lineages within the region were detected.
• The study identified several unique mutational profiles not previously observed elsewhere.

Conclusions:

• A lack of genomic sequencing data significantly hampered the understanding and response to the mpox outbreak.
• The developed nanopore sequencing approach enables near real-time mpox tracking and rapid lineage discovery.
• This methodology provides a scalable model for genomic surveillance of various viruses during future outbreaks.