Persistent systemic rotavirus vaccine infection in a child with X-linked severe combined immunodeficiency

Tetsushi Yoshikawa, Masaru Ihira, Yuki Higashimoto, Fumihiko Hattori, Hiroki Miura, Ken Sugata, Satoshi Komoto, Koki Taniguchi, Akihiro Iguchi, Masafumi Yamada, Tadashi Ariga

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3 Citations (Scopus)

Abstract

Objective: The main aims of the present study were to elucidate the systemic group A rotavirus (RVA) infection and to clarify the genetic changes of persistent virus in the X-linked severe combined immunodeficiency (SCID) patient. Methods: RotaTeq vaccine (RV5) genotype-specific real-time reverse transcription polymerase chain reaction was used to monitor viral RNA load in serially collected serum and stool samples. Next-generation sequence analysis was used to determine the genotype of the virus by sequencing 11 gene segments. Polyacrylamide gel electrophoresis (PAGE) analysis was used to identify rearrangement of viral genes. The gene rearrangement was examined in NSP5 gene by using Sanger sequence. Results: A 7-month-old boy demonstrated chronic diarrhea following the third administration of RV5 and failure to thrive. He was diagnosed with X-linked SCID and successfully underwent cord blood transplantation. High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples and the kinetics of viral RNA loads were correlated with the degree of clinical disease. Next-generation sequence analysis revealed genetic reassortment at least between the strains WI79-9/G1P7[5] and WI79-4/G6P1A[8] in the VP7 gene and the VP4 gene among the vaccine-derived rotavirus strains. In addition, PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis. Conclusions: The kinetics of RVA RNA load in serum and stool samples was consistent with the clinical course of the patient. Among five genotypes of RV5 vaccine, G1 genotype replicated well in this patient. Reassortment and rearrangements were demonstrated in persistently infected G1 genotype of RV5.

Original languageEnglish
Pages (from-to)1008-1013
Number of pages6
JournalJournal of Medical Virology
Volume91
Issue number6
DOIs
Publication statusPublished - 01-06-2019

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X-Linked Combined Immunodeficiency Diseases
Rotavirus Vaccines
Rotavirus Infections
Genotype
Genes
Sequence Analysis
Viral RNA
Viral Load
Polyacrylamide Gel Electrophoresis
Vaccines
Serum
RNA
Viruses
Failure to Thrive
Viral Genes
Gene Rearrangement
Fetal Blood
Reverse Transcription
Diarrhea
Transplantation

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Cite this

Yoshikawa, Tetsushi ; Ihira, Masaru ; Higashimoto, Yuki ; Hattori, Fumihiko ; Miura, Hiroki ; Sugata, Ken ; Komoto, Satoshi ; Taniguchi, Koki ; Iguchi, Akihiro ; Yamada, Masafumi ; Ariga, Tadashi. / Persistent systemic rotavirus vaccine infection in a child with X-linked severe combined immunodeficiency. In: Journal of Medical Virology. 2019 ; Vol. 91, No. 6. pp. 1008-1013.
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Persistent systemic rotavirus vaccine infection in a child with X-linked severe combined immunodeficiency. / Yoshikawa, Tetsushi; Ihira, Masaru; Higashimoto, Yuki; Hattori, Fumihiko; Miura, Hiroki; Sugata, Ken; Komoto, Satoshi; Taniguchi, Koki; Iguchi, Akihiro; Yamada, Masafumi; Ariga, Tadashi.

In: Journal of Medical Virology, Vol. 91, No. 6, 01.06.2019, p. 1008-1013.

Research output: Contribution to journalArticle

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T1 - Persistent systemic rotavirus vaccine infection in a child with X-linked severe combined immunodeficiency

AU - Yoshikawa, Tetsushi

AU - Ihira, Masaru

AU - Higashimoto, Yuki

AU - Hattori, Fumihiko

AU - Miura, Hiroki

AU - Sugata, Ken

AU - Komoto, Satoshi

AU - Taniguchi, Koki

AU - Iguchi, Akihiro

AU - Yamada, Masafumi

AU - Ariga, Tadashi

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Objective: The main aims of the present study were to elucidate the systemic group A rotavirus (RVA) infection and to clarify the genetic changes of persistent virus in the X-linked severe combined immunodeficiency (SCID) patient. Methods: RotaTeq vaccine (RV5) genotype-specific real-time reverse transcription polymerase chain reaction was used to monitor viral RNA load in serially collected serum and stool samples. Next-generation sequence analysis was used to determine the genotype of the virus by sequencing 11 gene segments. Polyacrylamide gel electrophoresis (PAGE) analysis was used to identify rearrangement of viral genes. The gene rearrangement was examined in NSP5 gene by using Sanger sequence. Results: A 7-month-old boy demonstrated chronic diarrhea following the third administration of RV5 and failure to thrive. He was diagnosed with X-linked SCID and successfully underwent cord blood transplantation. High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples and the kinetics of viral RNA loads were correlated with the degree of clinical disease. Next-generation sequence analysis revealed genetic reassortment at least between the strains WI79-9/G1P7[5] and WI79-4/G6P1A[8] in the VP7 gene and the VP4 gene among the vaccine-derived rotavirus strains. In addition, PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis. Conclusions: The kinetics of RVA RNA load in serum and stool samples was consistent with the clinical course of the patient. Among five genotypes of RV5 vaccine, G1 genotype replicated well in this patient. Reassortment and rearrangements were demonstrated in persistently infected G1 genotype of RV5.

AB - Objective: The main aims of the present study were to elucidate the systemic group A rotavirus (RVA) infection and to clarify the genetic changes of persistent virus in the X-linked severe combined immunodeficiency (SCID) patient. Methods: RotaTeq vaccine (RV5) genotype-specific real-time reverse transcription polymerase chain reaction was used to monitor viral RNA load in serially collected serum and stool samples. Next-generation sequence analysis was used to determine the genotype of the virus by sequencing 11 gene segments. Polyacrylamide gel electrophoresis (PAGE) analysis was used to identify rearrangement of viral genes. The gene rearrangement was examined in NSP5 gene by using Sanger sequence. Results: A 7-month-old boy demonstrated chronic diarrhea following the third administration of RV5 and failure to thrive. He was diagnosed with X-linked SCID and successfully underwent cord blood transplantation. High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples and the kinetics of viral RNA loads were correlated with the degree of clinical disease. Next-generation sequence analysis revealed genetic reassortment at least between the strains WI79-9/G1P7[5] and WI79-4/G6P1A[8] in the VP7 gene and the VP4 gene among the vaccine-derived rotavirus strains. In addition, PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis. Conclusions: The kinetics of RVA RNA load in serum and stool samples was consistent with the clinical course of the patient. Among five genotypes of RV5 vaccine, G1 genotype replicated well in this patient. Reassortment and rearrangements were demonstrated in persistently infected G1 genotype of RV5.

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