Probing the Viromic Frontiers

ABSTRACT Modern molecular technology, and particularly high-throughput sequencing (HTS), has revolutionized virus discovery and expanded the depth and breadth of the virome. Recent HTS was used to identify and discover a previously undescribed member of the family Flaviviridae that has genomic features characteristic of both hepaciviruses and pegiviruses. This virus, designated human hepegivirus-1 (HHpgV-1), may represent a previously undescribed new genus in the Flaviviridae family with implications for public health and blood supply safety. Detecting uncharacterized viruses such as HHpgV-1 in clinical samples requires an unbiased screening method that is as sensitive as PCR, while simultaneously detecting multiple rare viral sequences. The virome-capture-sequencing platform for vertebrate viruses (VirCapSeq-VERT) uses positive-selection oligonucleotide capture to sensitively detect sequences from every known vertebrate virus, even in high-background specimens with low-abundance viruses. VirCapSeq-VERT can also detect uncharacterized viruses with sequence homology to known viruses, enabling a new paradigm for virus detection