Multiplex PCR-Based Nanopore Sequencing and Epidemiological Surveillance of Hantaan orthohantavirus in Apodemus agrarius, Republic of Korea

Viruses. 2021 May 6;13(5):847. doi: 10.3390/v13050847.

Abstract

Whole-genome sequencing of infectious agents enables the identification and characterization of emerging viruses. The MinION device is a portable sequencer that allows real-time sequencing in fields or hospitals. Hantaan orthohantavirus (Hantaan virus, HTNV), harbored by Apodemus agrarius, causes hemorrhagic fever with renal syndrome (HFRS) and poses a critical public health threat worldwide. In this study, we aimed to evaluate the feasibility of using nanopore sequencing for whole-genome sequencing of HTNV from samples having different viral copy numbers. Amplicon-based next-generation sequencing was performed in A. agrarius lung tissues collected from the Republic of Korea. Genomic sequences of HTNV were analyzed based on the viral RNA copy numbers. Amplicon-based nanopore sequencing provided nearly full-length genomic sequences of HTNV and showed sufficient read depth for phylogenetic analysis after 8 h of sequencing. The average identity of the HTNV genome sequences for the nanopore sequencer compared to those of generated from Illumina MiSeq revealed 99.8% (L and M segments) and 99.7% (S segment) identities, respectively. This study highlights the potential of the portable nanopore sequencer for rapid generation of accurate genomic sequences of HTNV for quicker decision making in point-of-care testing of HFRS patients during a hantavirus outbreak.

Keywords: Hantaan virus (HTNV); MinION sequencing; amplicon-based NGS; genetic diversity; hemorrhagic fever with renal syndrome (HFRS); next-generation sequencing (NGS); phylogenetic analysis; viral genome surveillance; whole-genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Reservoirs / virology
  • Genetic Variation
  • Genome, Viral
  • Geography, Medical
  • Hantaan virus / classification
  • Hantaan virus / genetics*
  • Hemorrhagic Fever with Renal Syndrome / epidemiology*
  • Hemorrhagic Fever with Renal Syndrome / transmission
  • Hemorrhagic Fever with Renal Syndrome / virology*
  • High-Throughput Nucleotide Sequencing
  • Multiplex Polymerase Chain Reaction
  • Murinae / virology*
  • Phylogeny
  • Phylogeography
  • Prevalence
  • Public Health Surveillance
  • Republic of Korea / epidemiology
  • Rodentia / virology
  • Viral Load