title: Unbiased metagenomic sequencing complements specific routine diagnostic methods and increases chances to detect rare viral strains.
abstract: Multiplex PCR assays for respiratory viruses are widely used in routine diagnostics, as they are highly sensitive, rapid, and cost effective. However, depending on the assay system, cross-reactivity between viruses that share a high sequence homology as well as detection of rare virus isolates with sequence variations can be problematic. Virus sequence-independent metagenomic high-throughput sequencing allows for accurate detection of all virus species in a given sample, as we demonstrate here for human Enterovirus and Rhinovirus in a lung transplant patient. While early in infection a commercial PCR assay recorded Rhinovirus, high-throughput sequencing correctly identified human Enterovirus C104 as the source of infection, highlighting the potential of the technology and the benefit of applying open assay formats in complex diagnostic situations.
authors.affiliation: Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Dagmara W
authors.initials: DW
authors.lastname: Lewandowska
authors.affiliation: Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Zagordi
authors.affiliation: Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zbinden
authors.affiliation: Division of Pulmonary Medicine, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Macé M
authors.initials: MM
authors.lastname: Schuurmans
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Schreiber
authors.affiliation: Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Fabienne-Desirée
authors.initials: FD
authors.lastname: Geissberger
authors.affiliation: Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Huder
authors.affiliation: Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Böni
authors.affiliation: Division of Pulmonary Medicine, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Benden
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. Electronic address: nicolas.mueller@usz.ch.
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Mueller
authors.affiliation: Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: trkola.alexandra@virology.uzh.ch.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Trkola
authors.affiliation: Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: huber.michael@virology.uzh.ch.
authors.forename: Michael
authors.initials: M
authors.lastname: Huber
mesh_terms: D004770:Enterovirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D004769:Enterovirus Infections / Q000175:diagnosis* / Q000821:virology; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects; D008297:Male; D056186:Metagenomics / Q000379:methods*; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000175:diagnosis* / Q000821:virology
keywords: Enterovirus; Metagenomic; Next generation sequencing; PCR; Rhinovirus; Virus diagnostic