Human pegivirus 2 exhibits minimal geographic and temporal genetic diversity

Virology. 2020 Jan 2;539:69-79. doi: 10.1016/j.virol.2019.10.012. Epub 2019 Oct 31.


We applied an NGS based target capture approach to amplify HPgV-2 sequences from metagenomic libraries and enable full genome characterization. Despite expanded geographical sampling, sequence variability remains low, with diversity concentrated in approximately 3.3% of all amino acids. Serial samples from one HPgV-2 positive individual co-infected with comparable titers of HIV, HCV, and GBV-C showed that HPgV-2 remains highly stable over several weeks compared to other RNA viruses, despite a similarly error-prone polymerase. The consistent epidemiological association with and structural similarities to HCV, and the weak positive correlation of HCV and HPgV-2 titers shown here, suggests it may benefit from co-infection. While minimal selective pressure on HPgV-2 to evolve could suggest fitness, the rarity of HPgV-2 and the tight phylogenetic clustering of global strains likely indicates origination from a common source and a virus that is ill-suited to its host. Sporadic infections may explain the limited genetic diversity observed worldwide.

Keywords: Hepatitis C virus; Next-generation sequencing; Pegivirus; Viral diversity; xGen target enrichment.

MeSH terms

  • Coinfection / virology
  • Flaviviridae / classification
  • Flaviviridae / genetics*
  • Flaviviridae Infections / virology
  • Genetic Variation
  • Genome, Viral / genetics
  • Geography
  • Hepatitis C / virology
  • Humans
  • Phylogeny
  • RNA Viruses / genetics
  • RNA, Viral / genetics
  • Sequence Analysis, RNA
  • Viral Load
  • Viral Proteins / genetics


  • RNA, Viral
  • Viral Proteins