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Title: A novel variant of torque teno virus 7 identified in patients with Kawasaki disease

Abstract

Kawasaki disease (KD), first identified in 1967, is a pediatric vasculitis of unknown etiology that has an increasing incidence in Japan and many other countries. KD can cause coronary artery aneurysms. Its epidemiological characteristics, such as seasonality and clinical picture of acute systemic inflammation with prodromal intestinal/respiratory symptoms, suggest an infectious etiology for KD. Interestingly, multiple host genotypes have been identified as predisposing factors for KD. To explore experimental methodology for identifying etiological agent(s) for KD and to optimize epidemiological study design (particularly the sample size) for future studies, we conducted a pilot study. For a 1-year period, we prospectively enrolled 11 patients with KD. To each KD patient, we assigned two control individuals (one with diarrhea and the other with respiratory infections), matched for age, sex, and season of diagnosis. During the acute phase of disease, we collected peripheral blood, nasopharyngeal aspirate, and feces. We also determined genotypes, to identify those that confer susceptibility to KD. There was no statistically significant difference in the frequency of the risk genotypes between KD patients and control subjects. We also used unbiased metagenomic sequencing to analyze these samples. Metagenomic sequencing and PCR detected torque teno virus 7 (TTV7) in two patients withmore » KD (18%), but not in control subjects (P = 0.111). Sanger sequencing revealed that the TTV7 found in the two KD patients contained almost identical variants in nucleotide and identical changes in resulting amino acid, relative to the reference sequence. Additionally, we estimated the sample size that would be required to demonstrate a statistical correlation between TTV7 and KD. Future larger scale studies with carefully optimized metagenomic sequencing experiments and adequate sample size are warranted to further examine the association between KD and potential pathogens, including TTV7.« less

Authors:
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [1]; ORCiD logo [3]; ORCiD logo [1]; ORCiD logo [1];  [3];  [1]; ORCiD logo [2];  [3]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  2. Univ. of Tokyo (Japan). Dept. of Biological Sciences
  3. Japan Community Health Care Organization Osaka Hospital, Osaka (Japan). Dept. of Pediatrics
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1512604
Report Number(s):
LLNL-JRNL-764541
Journal ID: ISSN 1932-6203; 954438
Grant/Contract Number:  
AC52-07NA27344
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 13; Journal Issue: 12; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Thissen, James B., Isshiki, Mariko, Jaing, Crystal, Nagao, Yoshiro, Lebron Aldea, Dayanara, Allen, Jonathan E., Izui, Masafumi, Slezak, Thomas R., Ishida, Takafumi, and Sano, Tetsuya. A novel variant of torque teno virus 7 identified in patients with Kawasaki disease. United States: N. p., 2018. Web. doi:10.1371/journal.pone.0209683.
Thissen, James B., Isshiki, Mariko, Jaing, Crystal, Nagao, Yoshiro, Lebron Aldea, Dayanara, Allen, Jonathan E., Izui, Masafumi, Slezak, Thomas R., Ishida, Takafumi, & Sano, Tetsuya. A novel variant of torque teno virus 7 identified in patients with Kawasaki disease. United States. doi:10.1371/journal.pone.0209683.
Thissen, James B., Isshiki, Mariko, Jaing, Crystal, Nagao, Yoshiro, Lebron Aldea, Dayanara, Allen, Jonathan E., Izui, Masafumi, Slezak, Thomas R., Ishida, Takafumi, and Sano, Tetsuya. Fri . "A novel variant of torque teno virus 7 identified in patients with Kawasaki disease". United States. doi:10.1371/journal.pone.0209683. https://www.osti.gov/servlets/purl/1512604.
@article{osti_1512604,
title = {A novel variant of torque teno virus 7 identified in patients with Kawasaki disease},
author = {Thissen, James B. and Isshiki, Mariko and Jaing, Crystal and Nagao, Yoshiro and Lebron Aldea, Dayanara and Allen, Jonathan E. and Izui, Masafumi and Slezak, Thomas R. and Ishida, Takafumi and Sano, Tetsuya},
abstractNote = {Kawasaki disease (KD), first identified in 1967, is a pediatric vasculitis of unknown etiology that has an increasing incidence in Japan and many other countries. KD can cause coronary artery aneurysms. Its epidemiological characteristics, such as seasonality and clinical picture of acute systemic inflammation with prodromal intestinal/respiratory symptoms, suggest an infectious etiology for KD. Interestingly, multiple host genotypes have been identified as predisposing factors for KD. To explore experimental methodology for identifying etiological agent(s) for KD and to optimize epidemiological study design (particularly the sample size) for future studies, we conducted a pilot study. For a 1-year period, we prospectively enrolled 11 patients with KD. To each KD patient, we assigned two control individuals (one with diarrhea and the other with respiratory infections), matched for age, sex, and season of diagnosis. During the acute phase of disease, we collected peripheral blood, nasopharyngeal aspirate, and feces. We also determined genotypes, to identify those that confer susceptibility to KD. There was no statistically significant difference in the frequency of the risk genotypes between KD patients and control subjects. We also used unbiased metagenomic sequencing to analyze these samples. Metagenomic sequencing and PCR detected torque teno virus 7 (TTV7) in two patients with KD (18%), but not in control subjects (P = 0.111). Sanger sequencing revealed that the TTV7 found in the two KD patients contained almost identical variants in nucleotide and identical changes in resulting amino acid, relative to the reference sequence. Additionally, we estimated the sample size that would be required to demonstrate a statistical correlation between TTV7 and KD. Future larger scale studies with carefully optimized metagenomic sequencing experiments and adequate sample size are warranted to further examine the association between KD and potential pathogens, including TTV7.},
doi = {10.1371/journal.pone.0209683},
journal = {PLoS ONE},
number = 12,
volume = 13,
place = {United States},
year = {2018},
month = {12}
}

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Works referenced in this record:

Viral infections associated with Kawasaki disease
journal, March 2014

  • Chang, Luan-Yin; Lu, Chun-Yi; Shao, Pei-Lan
  • Journal of the Formosan Medical Association, Vol. 113, Issue 3
  • DOI: 10.1016/j.jfma.2013.12.008

Scalable metagenomic taxonomy classification using a reference genome database
journal, July 2013


Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome
journal, June 1975


Lack of Association Between Kawasaki Syndrome and Infection with Parvovirus b19, Human Herpesvirus 8, tt Virus, gb Virus C/Hepatitis g Virus or Chlamydia Pneumoniae
journal, January 2000


Using populations of human and microbial genomes for organism detection in metagenomes
journal, April 2015

  • Ames, Sasha K.; Gardner, Shea N.; Marti, Jose Manuel
  • Genome Research, Vol. 25, Issue 7
  • DOI: 10.1101/gr.184879.114

Molecular characterization of human Torque Teno virus
journal, August 2015

  • Wei, Youping; Chen, Minyang; Yang, Xia
  • Biomedical Reports, Vol. 3, Issue 6
  • DOI: 10.3892/br.2015.508

Genetics of Kawasaki Disease
journal, January 2012


CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice
journal, January 1994

  • Thompson, Julie D.; Higgins, Desmond G.; Gibson, Toby J.
  • Nucleic Acids Research, Vol. 22, Issue 22, p. 4673-4680
  • DOI: 10.1093/nar/22.22.4673

Evaluation of rapid and simple techniques for the enrichment of viruses prior to metagenomic virus discovery
journal, January 2014


Increased Prevalence of Anellovirus in Pediatric Patients with Fever
journal, November 2012


School-aged children with Kawasaki disease: High incidence of cervical lymphadenopathy and coronary artery involvement
journal, January 2003


Detection rate and clinical impact of respiratory viruses in children with Kawasaki disease
journal, January 2012


A Novel DNA Virus (TTV) Associated with Elevated Transaminase Levels in Posttransfusion Hepatitis of Unknown Etiology
journal, December 1997

  • Nishizawa, Tsutomu; Okamoto, Hiroaki; Konishi, Keiko
  • Biochemical and Biophysical Research Communications, Vol. 241, Issue 1
  • DOI: 10.1006/bbrc.1997.7765

Accurate genome relative abundance estimation for closely related species in a metagenomic sample
journal, January 2014

  • Sohn, Michael B.; An, Lingling; Pookhao, Naruekamol
  • BMC Bioinformatics, Vol. 15, Issue 1
  • DOI: 10.1186/1471-2105-15-242

Associated Symptoms in the Ten Days Before Diagnosis of Kawasaki Disease
journal, April 2009


Kawasaki disease: What is the epidemiology telling us about the etiology?
journal, July 2005


Predicting the characteristics of the aetiological agent for Kawasaki disease from other paediatric infectious diseases in Japan
journal, July 2015


Modelling seasonal variations in the age and incidence of Kawasaki disease to explore possible infectious aetiologies
journal, March 2012

  • Pitzer, Virginia E.; Burgner, David; Viboud, Cécile
  • Proceedings of the Royal Society B: Biological Sciences, Vol. 279, Issue 1739
  • DOI: 10.1098/rspb.2011.2464

Coronary arthritis in mice following the systemic injection of group bLactobacillus casei cell walls in aqueous suspension
journal, June 1985

  • Lehman, Thomas J. A.; Walker, Sharyn M.; Mahnovski, Vladimir
  • Arthritis & Rheumatism, Vol. 28, Issue 6
  • DOI: 10.1002/art.1780280609

Characterization of a highly divergent TT virus genome
journal, September 2000


ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms
journal, December 2007

  • Onouchi, Yoshihiro; Gunji, Tomohiko; Burns, Jane C.
  • Nature Genetics, Vol. 40, Issue 1
  • DOI: 10.1038/ng.2007.59

Seasonality of Kawasaki Disease: A Global Perspective
journal, September 2013


A genome-wide association study identifies three new risk loci for Kawasaki disease
journal, March 2012

  • Onouchi, Yoshihiro; Ozaki, Kouichi; Burns, Jane C.
  • Nature Genetics, Vol. 44, Issue 5
  • DOI: 10.1038/ng.2220

Active or recent parvovirus B19 infection in children with Kawasaki disease
journal, May 1994


TT Virus in the Nasal Secretions of Children with Acute Respiratory Diseases: Relations to Viremia and Disease Severity
journal, February 2003


Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis
journal, March 2012

  • Lee, Yi-Ching; Kuo, Ho-Chang; Chang, Jeng-Sheng
  • Nature Genetics, Vol. 44, Issue 5
  • DOI: 10.1038/ng.2227

Coronary artery outcomes among children with Kawasaki disease in the United States and Japan
journal, October 2013

  • Ogata, Shohei; Tremoulet, Adriana H.; Sato, Yuichiro
  • International Journal of Cardiology, Vol. 168, Issue 4
  • DOI: 10.1016/j.ijcard.2013.06.027

MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0
journal, October 2013

  • Tamura, Koichiro; Stecher, Glen; Peterson, Daniel
  • Molecular Biology and Evolution, Vol. 30, Issue 12
  • DOI: 10.1093/molbev/mst197

Human parvovirus B19 infection in Kawasaki disease
journal, July 1994


Kawasaki Disease-Specific Molecules in the Sera Are Linked to Microbe-Associated Molecular Patterns in the Biofilms
journal, November 2014


Association of Kawasaki disease with tropospheric wind patterns
journal, November 2011

  • Rodó, Xavier; Ballester, Joan; Cayan, Dan
  • Scientific Reports, Vol. 1, Issue 1
  • DOI: 10.1038/srep00152

Design and Optimization of a Metagenomics Analysis Workflow for NVRAM
conference, May 2014

  • Ames, Sasha; Allen, Jonathan E.; Hysom, David A.
  • 2014 IEEE International Parallel & Distributed Processing Symposium Workshops (IPDPSW)
  • DOI: 10.1109/IPDPSW.2014.200

A newly discovered human pneumovirus isolated from young children with respiratory tract disease
journal, June 2001

  • van den Hoogen, Bernadette G.; de Jong, Jan C.; Groen, Jan
  • Nature Medicine, Vol. 7, Issue 6
  • DOI: 10.1038/89098

Natural history of the TT virus infection through follow-up of TTV DNA–positive multiple-transfused patients
journal, January 2000

  • Lefrère, Jean-Jacques; Roudot-Thoraval, Françoise; Lefrère, François
  • Blood, Vol. 95, Issue 1
  • DOI: 10.1182/blood.V95.1.347