PMID- 28542207
OWN - NLM
STAT- MEDLINE
DCOM- 20170919
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 5
DP  - 2017
TI  - Metagenomic sequencing complements routine diagnostics in identifying viral 
      pathogens in lung transplant recipients with unknown etiology of respiratory 
      infection.
PG  - e0177340
LID - 10.1371/journal.pone.0177340 [doi]
LID - e0177340
AB  - BACKGROUND: Lung transplant patients are a vulnerable group of immunosuppressed 
      patients that are prone to frequent respiratory infections. We studied 60 
      episodes of respiratory symptoms in 71 lung transplant patients. Almost half of 
      these episodes were of unknown infectious etiology despite extensive routine 
      diagnostic testing. METHODS: We re-analyzed respiratory samples of all episodes 
      with undetermined etiology in order to detect potential viral pathogens 
      missed/not accounted for in routine diagnostics. Respiratory samples were 
      enriched for viruses by filtration and nuclease digestion, whole nucleic acids 
      extracted and randomly amplified before high throughput metagenomic virus 
      sequencing. Viruses were identified by a bioinformatic pipeline and confirmed and 
      quantified using specific real-time PCR. RESULTS: In completion of routine 
      diagnostics, we identified and confirmed a viral etiology of infection by our 
      metagenomic approach in four patients (three Rhinovirus A, one Rhinovirus B 
      infection) despite initial negative results in specific multiplex PCR. Notably, 
      the majority of samples were also positive for Torque teno virus (TTV) and Human 
      Herpesvirus 7 (HHV-7). While TTV viral loads increased with immunosuppression in 
      both throat swabs and blood samples, HHV-7 remained at low levels throughout the 
      observation period and was restricted to the respiratory tract. CONCLUSION: This 
      study highlights the potential of metagenomic sequencing for virus diagnostics in 
      cases with previously unknown etiology of infection and in complex diagnostic 
      situations such as in immunocompromised hosts.
FAU - Lewandowska, Dagmara W
AU  - Lewandowska DW
AD  - Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
FAU - Schreiber, Peter W
AU  - Schreiber PW
AD  - Division of Infectious Diseases and Hospital Epidemiology, University Hospital 
      Zurich, Zurich, Switzerland.
FAU - Schuurmans, Mace M
AU  - Schuurmans MM
AD  - Division of Pulmonary Medicine, University Hospital Zurich, Zurich, Switzerland.
FAU - Ruehe, Bettina
AU  - Ruehe B
AD  - Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
FAU - Zagordi, Osvaldo
AU  - Zagordi O
AD  - Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
FAU - Bayard, Cornelia
AU  - Bayard C
AD  - Division of Infectious Diseases and Hospital Epidemiology, University Hospital 
      Zurich, Zurich, Switzerland.
FAU - Greiner, Michael
AU  - Greiner M
AD  - Division of Infectious Diseases and Hospital Epidemiology, University Hospital 
      Zurich, Zurich, Switzerland.
FAU - Geissberger, Fabienne D
AU  - Geissberger FD
AD  - Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
FAU - Capaul, Riccarda
AU  - Capaul R
AD  - Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
FAU - Zbinden, Andrea
AU  - Zbinden A
AD  - Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
FAU - Boni, Jurg
AU  - Boni J
AD  - Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
FAU - Benden, Christian
AU  - Benden C
AD  - Division of Pulmonary Medicine, University Hospital Zurich, Zurich, Switzerland.
FAU - Mueller, Nicolas J
AU  - Mueller NJ
AD  - Division of Infectious Diseases and Hospital Epidemiology, University Hospital 
      Zurich, Zurich, Switzerland.
FAU - Trkola, Alexandra
AU  - Trkola A
AD  - Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
FAU - Huber, Michael
AU  - Huber M
AUID- ORCID: 0000-0002-0384-0000
AD  - Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20170523
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Adult
MH  - DNA Virus Infections/diagnosis/*virology
MH  - Female
MH  - Genome, Viral
MH  - Herpesvirus 7, Human/genetics/isolation & purification
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - *Lung Transplantation
MH  - Male
MH  - *Metagenome
MH  - Metagenomics
MH  - Middle Aged
MH  - Picornaviridae Infections/virology
MH  - Postoperative Complications/diagnosis/*virology
MH  - RNA Virus Infections/diagnosis/*virology
MH  - Respiratory Tract Infections/diagnosis/*virology
MH  - Rhinovirus/genetics/isolation & purification
MH  - Roseolovirus Infections/diagnosis/virology
MH  - Torque teno virus/genetics/isolation & purification
MH  - Transplant Recipients
PMC - PMC5441588
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/05/26 06:00
MHDA- 2017/09/20 06:00
PMCR- 2017/05/23
CRDT- 2017/05/26 06:00
PHST- 2017/01/16 00:00 [received]
PHST- 2017/04/26 00:00 [accepted]
PHST- 2017/05/26 06:00 [entrez]
PHST- 2017/05/26 06:00 [pubmed]
PHST- 2017/09/20 06:00 [medline]
PHST- 2017/05/23 00:00 [pmc-release]
AID - PONE-D-17-01984 [pii]
AID - 10.1371/journal.pone.0177340 [doi]
PST - epublish
SO  - PLoS One. 2017 May 23;12(5):e0177340. doi: 10.1371/journal.pone.0177340. 
      eCollection 2017.