The perils of pathogen discovery: Origin of a novel parvovirus-like hybrid genome traced to nucleic acid extraction spin columns

Samia N. Naccache, Alexander L. Greninger, Deanna Lee, Lark L Schneider, Tung Phan, Annie Rein-Weston, Andrew Aronsohn, John Hackett, Eric L. Delwart, Charles Y. Chiua

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

Next-generation sequencing was used for discovery and de novo assembly of a novel, highly divergent DNA virus at the interface between the Parvoviridae and Circoviridae. The virus, provisionally named parvovirus-like hybrid virus (PHV), is nearly identical by sequence to another DNA virus, NIH-CQV, previously detected in Chinese patients with seronegative (non-A-E) hepatitis. Although we initially detected PHV in a wide range of clinical samples, with all strains sharing ~99% nucleotide and amino acid identity with each other and with NIH-CQV, the exact origin of the virus was eventually traced to contaminated silica-binding spin columns used for nucleic acid extraction. Definitive confirmation of the origin of PHV, and presumably NIH-CQV, was obtained by in-depth analyses of water eluted through contaminated spin columns. Analysis of environmental metagenome libraries detected PHV sequences in coastal marine waters of North America, suggesting that a potential association between PHV and diatoms (algae) that generate the silica matrix used in the spin columns may have resulted in inadvertent viral contamination during manufacture. The confirmation of PHV/NIH-CQV as laboratory reagent contaminants and not bona fide infectious agents of humans underscores the rigorous approach needed to establish the validity of new viral genomes discovered by nextgeneration sequencing.

Original languageEnglish (US)
Pages (from-to)11966-11977
Number of pages12
JournalJournal of Virology
Volume87
Issue number22
DOIs
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Medicine(all)

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    Naccache, S. N., Greninger, A. L., Lee, D., Schneider, L. L., Phan, T., Rein-Weston, A., Aronsohn, A., Hackett, J., Delwart, E. L., & Chiua, C. Y. (2013). The perils of pathogen discovery: Origin of a novel parvovirus-like hybrid genome traced to nucleic acid extraction spin columns. Journal of Virology, 87(22), 11966-11977. https://doi.org/10.1128/JVI.02323-13