Patterns of mutation within an emerging endemic lineage of HEV-3a

J Viral Hepat. 2019 Jan;26(1):191-198. doi: 10.1111/jvh.13015. Epub 2018 Nov 14.

Abstract

The hepatitis E virus can cause chronic infections in immuno-suppressed patients, and cases have been on the rise globally. Viral mutations during such infections are difficult to characterize. We deep-sequenced viral populations from 15 immunocompromised patients with chronic HEV to identify the viral lineage and describe viral mutational hotspots within and across patients. A total of 21 viral RNA samples were collected between 2012 and 2017 from a single hospital in Singapore. Sequences covering a total of 3894 bp of the HEV genome were obtained. Phylogenetic analyses identified all sequences as belonging to the HEV-3a sub-clade and clearly indicate a unique local lineage. Deep sequencing reveals variable viral population complexity during infections. Comparisons of viral samples from the same patients spaced 2-19 months apart revealed rapid nucleotide replacements in the dominant viral sequence in both ribavirin treated and treatment-naive patients. Mutational hotspots were identified within ORF3 and the PCP/HVR domain of ORF1.

Keywords: chronic hepatitis E; liver disease; viral infection; viral mutation; zoonosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use
  • Chronic Disease
  • Genome, Viral
  • Genotype
  • Hepatitis E / blood
  • Hepatitis E / drug therapy
  • Hepatitis E / virology*
  • Hepatitis E virus / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunocompromised Host
  • Mutation*
  • Phylogeny*
  • RNA, Viral / genetics*
  • Singapore

Substances

  • Antiviral Agents
  • RNA, Viral

Associated data

  • GENBANK/AB437317.1
  • GENBANK/KT447528
  • GENBANK/KT447526
  • GENBANK/KT447527.1
  • GENBANK/AF082843