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Article: Neurological Disorders Associated with Human Alphaherpesviruses.

Kawada, Jun-Ichi

Advances in experimental medicine and biology

2018 Volume 1045, Page(s) 85–102

Abstract: Herpes simplex virus (HSV) encephalitis is the most common cause of sporadic fatal encephalitis worldwide, and central nervous system (CNS) involvement is observed in approximately one-third of neonatal HSV infections . In recent years, single-gene ... ...

Abstract	Herpes simplex virus (HSV) encephalitis is the most common cause of sporadic fatal encephalitis worldwide, and central nervous system (CNS) involvement is observed in approximately one-third of neonatal HSV infections . In recent years, single-gene inborn errors of innate immunity have been shown to be associated with susceptibility to HSV encephalitis . Temporal lobe abnormalities revealed by magnetic resonance imaging-the most sensitive imaging method for HSV encephalitis-are considered strong evidence for the disease. Detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction (PCR) is the gold standard for the diagnosis of HSV encephalitis and neonatal meningoencephalitis. Intravenous acyclovir for 14-21 days is the standard treatment in HSV encephalitis. Neurological outcomes in neonates are improved by intravenous high-dose acyclovir for 21 days followed by oral acyclovir suppressive therapy for 6 months. Varicella-zoster virus (VZV) causes a wide range of CNS manifestations. VZV encephalitis typically occurs after primary infection, and reactivation of VZV may cause encephalitis. On the other hand, VZV infection of cerebral arteries produces vasculopathy, which can manifest as ischemic stroke. Vasculopathy can occur after primary infection or reactivation of VZV. PCR detection of VZV DNA in the cerebrospinal fluid can be used for the diagnosis of encephalitis or vasculopathy. Although there are no controlled treatment trials to assess VZV treatments of encephalitis or vasculopathy, intravenous acyclovir is a common treatment.
MeSH term(s)	Alphaherpesvirinae/drug effects ; Alphaherpesvirinae/genetics ; Alphaherpesvirinae/physiology ; Animals ; Antiviral Agents/therapeutic use ; Herpesviridae Infections/diagnostic imaging ; Herpesviridae Infections/drug therapy ; Herpesviridae Infections/virology ; Humans ; Nervous System Diseases/diagnostic imaging ; Nervous System Diseases/drug therapy ; Nervous System Diseases/virology
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2018-06-12
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-981-10-7230-7_5
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Article ; Online: MicroRNA expression profiling of urine exosomes in children with congenital cytomegalovirus infection.

Torii, Yuka / Suzuki, Takako / Fukuda, Yuto / Haruta, Kazunori / Yamaguchi, Makoto / Horiba, Kazuhiro / Kawada, Jun-Ichi / Ito, Yoshinori

Scientific reports

2024 Volume 14, Issue 1, Page(s) 5475

Abstract: Congenital cytomegalovirus (cCMV) infection can damage the central nervous system in infants; however, its prognosis cannot be predicted from clinical evaluations at the time of birth. Urinary exosomes can be used to analyze neuronal damage in neuronal ... ...

Abstract	Congenital cytomegalovirus (cCMV) infection can damage the central nervous system in infants; however, its prognosis cannot be predicted from clinical evaluations at the time of birth. Urinary exosomes can be used to analyze neuronal damage in neuronal diseases. To investigate the extent of neuronal damage in patients with cCMV, exosomal miRNA expression in the urine was investigated in cCMV-infected infants and controls. Microarray analysis of miRNA was performed in a cohort of 30 infants, including 11 symptomatic cCMV (ScCMV), 7 asymptomatic cCMV (AScCMV), and one late-onset ScCMV cases, and 11 healthy controls (HC). Hierarchical clustering analysis revealed the distinct expression profile of ScCMV. The patient with late-onset ScCMV was grouped into the ScCMV cluster. Pathway enrichment analysis of the target mRNAs differed significantly between the ScCMV and HC groups; this analysis also revealed that pathways related to brain development were linked to upregulated pathways. Six miRNAs that significantly different between groups (ScCMV vs. HC and ScCMV vs. AScCMV) were selected for digital PCR in another cohort for further validation. Although these six miRNAs seemed insufficient for predicting ScCMV, expression profiles of urine exosomal miRNAs can reveal neurological damage in patients with ScCMV compared to those with AcCMV or healthy infants.
MeSH term(s)	Child ; Infant ; Humans ; Exosomes/genetics ; Body Fluids ; MicroRNAs/genetics ; Central Nervous System ; Cytomegalovirus Infections/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2024-03-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-56106-1
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Article: Diagnosis of Peripheral Facial Palsy Associated with Parvovirus B19 Infection by Polymerase Chain Reaction.

Fukuta, Taro / Kawano, Yoshihiko / Ikeda, Maiko / Kawada, Jun-Ichi / Ito, Yoshinori / Hara, Shinya

Case reports in pediatrics

2022 Volume 2022, Page(s) 4574640

Abstract: Human parvovirus B19 (PVB19) infection causes neurological manifestations, including encephalitis, meningitis, and neuropathy, but facial nerve palsy is rare. Moreover, no case of facial nerve palsy related to PVB19 infection that was diagnosed by PCR ... ...

Abstract	Human parvovirus B19 (PVB19) infection causes neurological manifestations, including encephalitis, meningitis, and neuropathy, but facial nerve palsy is rare. Moreover, no case of facial nerve palsy related to PVB19 infection that was diagnosed by PCR and serology has been reported. A 19-month-old boy without the medical history developed facial nerve palsy and was treated with prednisolone and valacyclovir. On the 19th day, erythema appeared on his body, and the PVB19-specific IgM and PVB19 DNA were detected in the serum, leading to the diagnosis of infectious erythema associated with PVB19 infection. This case indicates that PVB19 may be one of the causative agents of facial nerve palsy.
Language	English
Publishing date	2022-01-10
Publishing country	United States
Document type	Case Reports
ZDB-ID	2659094-3
ISSN	2090-6811 ; 2090-6803
ISSN (online)	2090-6811
ISSN	2090-6803
DOI	10.1155/2022/4574640
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Article ; Online: MicroRNA expression profiling of cerebrospinal fluid/serum exosomes in children with human herpesvirus 6-associated encephalitis/encephalopathy by high-throughput sequencing.

Torii, Yuka / Kawada, Jun-Ichi / Horiba, Kazuhiro / Okumura, Toshihiko / Suzuki, Takako / Ito, Yoshinori

Journal of neurovirology

2022 Volume 28, Issue 1, Page(s) 151–157

Abstract: Primary human herpesvirus 6 (HHV-6) infection is sometimes accompanied by acute encephalopathy with reduced subcortical diffusion (AED) in immunocompetent children. We investigated exosomal microRNA (miRNA) expression profiles in cerebrospinal fluid (CSF) ...

Abstract	Primary human herpesvirus 6 (HHV-6) infection is sometimes accompanied by acute encephalopathy with reduced subcortical diffusion (AED) in immunocompetent children. We investigated exosomal microRNA (miRNA) expression profiles in cerebrospinal fluid (CSF) and sera of patients with HHV-6-associated AED (n = 5) and febrile seizure (FS) (n = 5) using high-throughput sequencing. A total of 176 and 663 miRNAs were identified in CSF and serum exosomes, respectively. Comparative analysis determined that some miRNAs (miR-381-3p, miR-155) were exclusively expressed in the CSF exosomes of AED but not of FS patients, suggesting their potential application as novel diagnostic biomarkers for AED.
MeSH term(s)	Child ; Encephalitis, Viral/genetics ; Encephalitis, Viral/metabolism ; Exosomes/genetics ; Exosomes/metabolism ; Herpesvirus 6, Human/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; MicroRNAs/genetics ; Roseolovirus Infections/genetics
Chemical Substances	MIRN381 microRNA, human ; MicroRNAs
Language	English
Publishing date	2022-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1283265-0
ISSN	1538-2443 ; 1355-0284
ISSN (online)	1538-2443
ISSN	1355-0284
DOI	10.1007/s13365-022-01058-3
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Article ; Online: Association Between NUDT15 R139C Genotype and Neutropenia During Antiviral Therapy in Patients With Congenital Cytomegalovirus Infection.

Yamaguchi, Makoto / Iwata, Ken-Ichi / Fukuda, Yuto / Haruta, Kazunori / Suzuki, Takako / Torii, Yuka / Ito, Yoshinori / Kawada, Jun-Ichi

The Pediatric infectious disease journal

2023 Volume 42, Issue 7, Page(s) e256–e257

MeSH term(s)	Humans ; Genotype ; Neutropenia ; Cytomegalovirus Infections/drug therapy ; Antiviral Agents/adverse effects
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2023-03-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	392481-6
ISSN	1532-0987 ; 0891-3668
ISSN (online)	1532-0987
ISSN	0891-3668
DOI	10.1097/INF.0000000000003902
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Article ; Online: Proteomic Analysis Reveals Novel Plasma Biomarkers for Neurological Complications in Patients With Congenital Cytomegalovirus Infection.

Yamaguchi, Makoto / Suzuki, Takako / Kidokoro, Hiroyuki / Iwata, Ken-Ichi / Fukuda, Yuto / Haruta, Kazunori / Torii, Yuka / Ito, Yoshinori / Kawada, Jun-Ichi

Journal of the Pediatric Infectious Diseases Society

2023 Volume 12, Issue 10, Page(s) 525–533

Abstract: Background: Congenital cytomegalovirus (cCMV) infection is a leading cause of nonhereditary neurological complications. When considering antiviral treatment, it is important to differentiate between symptomatic and asymptomatic patients. This study ... ...

Abstract	Background: Congenital cytomegalovirus (cCMV) infection is a leading cause of nonhereditary neurological complications. When considering antiviral treatment, it is important to differentiate between symptomatic and asymptomatic patients. This study aimed to identify candidate plasma biomarkers for neurological complications of cCMV infection using proteomic analysis. Methods: This study retrospectively enrolled five patients with symptomatic cCMV infection, four with asymptomatic cCMV infection with isolated sensorineural hearing loss (SNHL), and five with asymptomatic cCMV infection. The plasma samples were collected during neonatal period. The peptides were analyzed using liquid chromatography-mass spectrometry. The concentrations of differentially expressed proteins were validated using an enzyme-linked immunosorbent assay. Results: A total of 456 proteins were identified and quantified. The levels of 80 proteins were significantly different between patients with and without cCMV-related symptoms including isolated SNHL. The levels of 31 proteins were significantly different between patients with and without neuroimaging abnormalities. The plasma concentrations of Fms-related receptor tyrosine kinase 4 in patients with cCMV-related symptoms were significantly higher than those in patients with asymptomatic cCMV infection. Moreover, plasma peptidylprolyl isomerase A levels were significantly higher in patients with neuroimaging abnormalities than in those without. Conclusions: Proteomic analysis of patients with cCMV infection showed that Fms-related receptor tyrosine kinase 4 and peptidylprolyl isomerase A could be novel diagnostic biomarkers for neurological complications of cCMV infection.
MeSH term(s)	Infant, Newborn ; Humans ; Infant ; Cytomegalovirus ; Retrospective Studies ; Proteomics ; Cytomegalovirus Infections/congenital ; Hearing Loss, Sensorineural/diagnosis ; Hearing Loss, Sensorineural/etiology ; Biomarkers ; Peptidylprolyl Isomerase ; Protein-Tyrosine Kinases
Chemical Substances	Biomarkers ; Peptidylprolyl Isomerase (EC 5.2.1.8) ; Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2023-09-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2668791-4
ISSN	2048-7207 ; 2048-7193
ISSN (online)	2048-7207
ISSN	2048-7193
DOI	10.1093/jpids/piad074
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Article: Time course of skin rash, computed tomography findings, and viral load in a rheumatoid arthritis patient with severe varicella pneumonia.

Kobayashi, Hironori / Takeuchi, Shunta / Torii, Yuka / Ikenouchi, Tadasuke / Kawada, Jun-Ichi / Oka, Keisuke / Kato, Sayaka / Ogawa, Masahiro

IDCases

2023 Volume 33, Page(s) e01866

Abstract: Varicella-zoster virus (VZV) infection in adults or immunocompromised patients has a more severe presentation compared to the mild disease in children. To the best of our knowledge, no reports have described the clinical course of VZV pneumonia focusing ... ...

Abstract	Varicella-zoster virus (VZV) infection in adults or immunocompromised patients has a more severe presentation compared to the mild disease in children. To the best of our knowledge, no reports have described the clinical course of VZV pneumonia focusing on time course of skin rash, chest computed tomography (CT) findings, and viral load. Furthermore, no reports have described the reactivation of human herpes virus 6 (HHV-6) in VZV pneumonia. Here, we report a case of severe VZV pneumonia that resulted in reactivation of HHV-6 in a patient with rheumatoid arthritis (RA). A 66-year-old female treated for RA was admitted to our hospital with papules. Her chest CT showed granular infiltrates, micronodules, and ground-glass opacities. The day after admission, because the typical skin rashes and chest CT findings were observed, she was diagnosed with VZV pneumonia and treated with acyclovir. Her skin rash then crusted over five days and entered the healing process, whereas it took approximately two weeks for her respiratory condition and chest CT findings to improve. In addition, VZV deoxyribonucleic acid (DNA) gradually decreased with treatment. On the 34th day of admission, VZV DNA was not found in the serum sample but remained in the sputum sample. Furthermore, although reactivation of HHV-6 was observed, viremia resolved without treatment. Clinicians should be able to recognize the differences in the improvement of skin rashes, respiratory status, and chest CT findings. In addition, treatment for HHV-6 reactivation should be carefully determined for each case.
Language	English
Publishing date	2023-07-29
Publishing country	Netherlands
Document type	Case Reports
ZDB-ID	2745454-X
ISSN	2214-2509
ISSN	2214-2509
DOI	10.1016/j.idcr.2023.e01866
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Article ; Online: Diagnostic and disease severity determination criteria for hydroa vacciniforme lymphoproliferative disorders and severe mosquito bite allergy.

Hirai, Yoji / Asada, Hideo / Hamada, Toshihisa / Kawada, Jun-Ichi / Kimura, Hiroshi / Arai, Ayako / Ohshima, Koichi / Ohga, Shouichi / Iwatsuki, Keiji

The Journal of dermatology

2023 Volume 50, Issue 7, Page(s) e198–e205

Abstract: Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) and severe mosquito bite allergy (SMBA) are both cutaneous forms of Epstein-Barr virus (EBV)-associated T/natural killer (NK) cell LPDs and are closely related to chronic active EBV disease (CAEBV) ...

Abstract	Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) and severe mosquito bite allergy (SMBA) are both cutaneous forms of Epstein-Barr virus (EBV)-associated T/natural killer (NK) cell LPDs and are closely related to chronic active EBV disease (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). HV-LPD is further divided into classic HV, a benign subtype mediated by EBV-positive γδT cells, and systemic HV, another life-threatening subtype mainly associated with EBV-positive αβT or γδT cells. The vast majority of patients with SMBA have increased numbers of EBV-infected NK cells in the blood. Clinical symptoms of HV-LPD and SMBA often overlap in the same patient and may progress to more serious disease conditions equivalent to the systemic form of CAEBV. To define the disease spectrum of HV-LPD and SMBA, we propose the diagnostic criteria and the determination criteria for disease severity. The proposed diagnostic criteria are consistent with those for CAEBV and EBV-HLH in the guidelines for the management for CAEBV and related disorders 2023.
MeSH term(s)	Humans ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/diagnosis ; Herpesvirus 4, Human ; Hydroa Vacciniforme/diagnosis ; Hydroa Vacciniforme/complications ; Insect Bites and Stings/complications ; Insect Bites and Stings/diagnosis ; Patient Acuity ; Lymphoproliferative Disorders/diagnosis ; Hypersensitivity/diagnosis ; Hypersensitivity/complications
Language	English
Publishing date	2023-05-30
Publishing country	England
Document type	Journal Article
ZDB-ID	800103-0
ISSN	1346-8138 ; 0385-2407
ISSN (online)	1346-8138
ISSN	0385-2407
DOI	10.1111/1346-8138.16842
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Zs.B 1950: Show issues

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Article ; Online: Comparison of plasma proteomic profiles of patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and infectious mononucleosis.

Haruta, Kazunori / Suzuki, Takako / Yamaguchi, Makoto / Fukuda, Yuto / Torii, Yuka / Takahashi, Yoshiyuki / Ito, Yoshinori / Kawada, Jun-Ichi

Journal of medical virology

2023 Volume 96, Issue 2, Page(s) e29450

Abstract: Primary Epstein-Barr virus (EBV) infection occasionally causes EBV-infectious mononucleosis (EBV-IM) and EBV-hemophagocytic lymphohistiocytosis (EBV-HLH). Although EBV-IM is mostly mild and self-limiting, EBV-HLH is a life-threatening disease ... ...

Abstract	Primary Epstein-Barr virus (EBV) infection occasionally causes EBV-infectious mononucleosis (EBV-IM) and EBV-hemophagocytic lymphohistiocytosis (EBV-HLH). Although EBV-IM is mostly mild and self-limiting, EBV-HLH is a life-threatening disease characterized by excessive immune activation. However, the pathogenesis of EBV-HLH is yet to be fully elucidated. A diagnostic biomarker for EBV-HLH is desirable because early diagnosis and treatment are critical for the effective management of patients. In this study, the proteomic profiling of plasma was performed using liquid chromatography-mass spectrometry to identify proteins specific to EBV-IM and EBV-HLH. Furthermore, pathway analysis was performed for the proteins upregulated in patients with EBV-IM and EBV-HLH. Compared to healthy controls, 63 and 18 proteins were upregulated in patients with EBV-IM and EBV-HLH, respectively. Pathway and process enrichment analyses revealed that the complement system was the most enriched category of upregulated proteins in EBV-IM, whereas proteins related to immune effector processes were the most enriched in EBV-HLH. Among the 18 proteins upregulated in EBV-HLH, seven were exclusive to EBV-HLH. These specific proteins were associated with three pathways, and apolipoprotein E was commonly found in all the pathways. Proteomic analysis may provide new insights into the host response to EBV infection and the pathogenesis of EBV-related diseases.
MeSH term(s)	Humans ; Herpesvirus 4, Human/genetics ; Infectious Mononucleosis/complications ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/diagnosis ; Proteomics
Language	English
Publishing date	2023-10-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.29450
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Zs.A 1320: Show issues

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Article: Comparison of Whole Blood and Plasma for Monitoring Cytomegalovirus and Epstein-Barr Virus.

Fukuda, Yuto / Torii, Yuka / Iwata, Ken-Ichi / Haruta, Kazunori / Yamaguchi, Makoto / Suzuki, Takako / Narita, Atsushi / Muramatsu, Hideki / Ogura, Yasuhiro / Takahashi, Yoshiyuki / Ito, Yoshinori / Kawada, Jun-Ichi

The new microbiologica

2024 Volume 47, Issue 1, Page(s) 52–59

Abstract: Monitoring Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection after transplantation is recommended to enable preemptive therapy. However, the most suitable sample type remains unclear. Patients who underwent hematopoietic stem cell or liver ... ...

Abstract	Monitoring Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection after transplantation is recommended to enable preemptive therapy. However, the most suitable sample type remains unclear. Patients who underwent hematopoietic stem cell or liver transplantation were included in this study. Viral loads in sequential whole-blood and plasma samples were retrospectively analyzed. EBV DNA was detected more frequently in whole blood (55%) than in plasma (18%). The detection rate of CMV DNA was similar between the two sample types. The correlation of viral loads between the two sample types were 0.515 and 0.688 for EBV and CMV, respectively. Among paired samples in which EBV DNA was detected in whole blood, the plasma EBV detection rate was significantly higher in patients who underwent hematopoietic stem cell transplantation than in those who underwent liver transplantation. The viral DNA load in whole blood and plasma showed similar trends. The EBV detection rate was higher in whole blood, and a high correlation was observed between CMV DNA loads and whole blood and plasma. These results indicate that whole blood is more sensitive for monitoring both EBV and CMV, whereas plasma is a potential alternative sample for monitoring CMV.
MeSH term(s)	Humans ; Cytomegalovirus/genetics ; Cytomegalovirus/isolation & purification ; Cytomegalovirus Infections/virology ; Cytomegalovirus Infections/blood ; Cytomegalovirus Infections/diagnosis ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/isolation & purification ; Epstein-Barr Virus Infections/virology ; Epstein-Barr Virus Infections/blood ; Epstein-Barr Virus Infections/diagnosis ; Male ; Female ; Middle Aged ; Adult ; Viral Load ; Retrospective Studies ; DNA, Viral/blood ; Young Adult ; Hematopoietic Stem Cell Transplantation ; Aged ; Plasma/virology ; Liver Transplantation ; Adolescent
Chemical Substances	DNA, Viral
Language	English
Publishing date	2024-05-03
Publishing country	Italy
Document type	Journal Article ; Comparative Study
ZDB-ID	756168-4
ISSN	1121-7138 ; 0391-5352
ISSN	1121-7138 ; 0391-5352
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