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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.
@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:

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