MDPIActa Medica Okayama1999-49151412022Nectin-2 Acts as a Viral Entry Mediated Molecule That Binds to Human Herpesvirus 6B Glycoprotein B160ENHirohitoOgawaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeFujikuraSchool of Veterinary Medicine, Kitasato UniversityHikaruNambaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobukoYamashitaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyukiHondaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaoYamadaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHuman herpesvirus 6B (HHV-6B) is a T-lymphotropic virus and the etiological agent of exanthem subitum. HHV-6B is present in a latent or persistent form after primary infection and is produced in the salivary glands or transmitted to this organ. Infected individuals continue to secrete the virus in their saliva, which is thus considered a source for virus transmission. HHV-6B primarily propagates in T cells because its entry receptor, CD134, is mainly expressed by activated T cells. The virus then spreads to the host's organs, including the salivary glands, nervous system, and liver. However, CD134 expression is not detected in these organs. Therefore, HHV-6B may be entering cells via a currently unidentified cell surface molecule, but the mechanisms for this have not yet been investigated. In this study, we investigated a CD134-independent virus entry mechanism in the parotid-derived cell line HSY. First, we confirmed viral infection in CD134-membrane unanchored HSY cells. We then determined that nectin cell adhesion molecule 2 (nectin-2) mediated virus entry and that HHV-6B-insensitive T-cells transduced with nectin-2 were transformed into virus-permissive cells. We also found that virus entry was significantly reduced in nectin-2 knockout parotid-derived cells. Furthermore, we showed that HHV-6B glycoprotein B (gB) interacted with the nectin-2 V-set domain. The results suggest that nectin-2 acts as an HHV-6B entry-mediated protein.No potential conflict of interest relevant to this article was reported.The Japanese Society of Veterinary ScienceActa Medica Okayama0916-72508182019Risk assessment for hepatitis E virus infection from domestic pigs introduced into an experimental animal facility in a medical school11911196ENHirohitoOgawaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHarukoHirayamaDepartment of Animal Resources, Advanced Science Research Center, Okayama UniversitySatsukiTanakaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNorioYataDepartment of Animal Resources, Advanced Science Research Center, Okayama UniversityHikaruNambaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobukoYamashitaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenzoYonemitsuLaboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi UniversityKenMaedaLaboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi UniversityKatsumiMominokiDepartment of Animal Resources, Advanced Science Research Center, Okayama UniversityMasaoYamadaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Hepatitis E virus (HEV) is known to cause zoonotic infections from pigs, wild boars and deer. Domestic pigs have been used as an experimental animal model in medical research and training; however, the risks of HEV infection from pigs during animal experiments are largely unknown. Here, we retrospectively investigated the seroprevalence and detection rates of viral RNA in 73 domestic pigs (average 34.5 kg) introduced into an animal experimental facility in a medical school during 2012-2016. We detected anti-HEV immunoglobulin G antibodies in 24 of 73 plasma samples (32.9%), though none of the samples were positive for viral RNA. Plasma samples of 18 pigs were sequentially monitored and were classified into four patterns: sustained positive (5 pigs), sustained negative (5 pigs), conversion to positive (6 pigs) and conversion to negative (2 pigs). HEV genomes were detected in 2 of 4 liver samples from pigs that were transported from the same farm during 2016-2017. Two viral sequences of the overlapping open reading frame (ORF) 2/3 region (97 bp) were identical and phylogenetically fell into genotype 3. A 459-bp length of the ORF2 region of an amplified fragment from a pig transported in 2017 was clustered with the wbJYG1 isolate (subgenotype 3b) with 91.5% (420/459 bp) nucleotide identity. Based on our results, we suggest that domestic pigs introduced into animal facilities carry a potential risk of HEV infection to researchers, trainees and facility staff. Continuous surveillance and precautions are important to prevent HEV infection in animal facilities.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6952015Inhibitory Effects of Edaravone, a Free Radical Scavenger, on Cytokine-induced Hyperpermeability of Human Pulmonary Microvascular Endothelial Cells:A Comparison with Dexamethasone and Nitric Oxide Synthase Inhibitor279290ENYukieSaitoYousukeFujiiMasatoYashiroMitsuruTsugeNobuyukiNosakaNobukoYamashitaMutsukoYamadaHirokazuTsukaharaTsuneoMorishimaOriginal Article10.18926/AMO/53674Lung hyperpermeability affects the development of acute respiratory distress syndrome (ARDS), but therapeutic strategies for the control of microvascular permeability have not been established. We examined the effects of edaravone, dexamethasone, and N-monomethyl-L-arginine (L-NMMA) on permeability changes in human pulmonary microvascular endothelial cells (PMVEC) under a hypercytokinemic state. Human PMVEC were seeded in a Boyden chamber. After monolayer confluence was achieved, the culture media were replaced respectively by culture media containing edaravone, dexamethasone, and L-NMMA. After 24-h incubation, the monolayer was stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Fluorescein-labeled dextran was added. Then the trans-human PMVEC leak was measured. Expressions of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 protein (ZO-1) were evaluated using real-time quantitative polymerase chain reaction and immunofluorescence microscopy. The results showed that TNF-α＋IL-1β markedly increased pulmonary microvascular permeability. Pretreatment with edaravone, dexamethasone, or L-NMMA attenuated the hyperpermeability and inhibited the cytokine-induced reduction of VE-cadherin expression on immunofluorescence staining. Edaravone and dexamethasone increased the expression of ZO-1 at both the mRNA and protein levels. Edaravone and dexamethasone inhibited the permeability changes of human PMVEC, at least partly through an enhancement of VE-cadherin. Collectively, these results suggest a potential therapeutic approach for intervention in patients with ARDS.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812522013マウスインフルエンザ肺炎におけるレドックス制御蛋白チオレドキシン（TRX-1）の治療的効果109112ENMasatoYashiroHirokazuTsukaharaAkihiroMatsukawaMutsukoYamadaYosukeFujiiYoshiharuNagaokaMitsuruTsugeNobukoYamashitaToshihiroItoMasaoYamadaHiroshiMasutaniJunjiYodoiTsuneoMorishimaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama0090-34934112013Redox-Active Protein Thioredoxin-1 Administration Ameliorates Influenza A Virus (H1N1)-Induced Acute Lung Injury in Mice171181ENMasatoYashiroHirokazuTsukaharaAkihiroMatsukawaMutsukoYamadaYosukeFujiiYoshiharuNagaokaMitsuruTsugeNobukoYamashitaToshihiroItoMasaoYamadaHiroshiMasutaniObjectives: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice.
Design: Prospective animal trial.
Setting: Research laboratory.
Subjects: Nine-week-old male C57BL/6 mice inoculated with H1N1.
Intervention: The mice were divided into a vehicle-treated group and recombinant human thioredoxin-1-treated group. For survival rate analysis, the vehicle or recombinant human thioredoxin-1 was administered intraperitoneally every second day from day -1 to day 13. For lung lavage and pathological analyses, vehicle or recombinant human thioredoxin-1 was administered intraperitoneally on days 1, 1, and 3.
Measurements and Main Results: Lung lavage and pathological analyses were performed at 24, 72, and 120 hrs after inoculation. The recombinant human thioredoxin-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of tumor necrosis factor-a and chemokine (C-X-C motif) ligand 1 in the lung and oxidative stress enhancement, which were observed in H1N1-inoculated mice. H1N1 induced expressions of tumor necrosis factor-a and chemokine (C-X-C motif) ligand 1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of recombinant human thioredoxin-1. The recombinant human thioredoxin-1 treatment started 30 mins after H1N1 inoculation also significantly improved the survival of the mice.
Conclusions: Exogenous administration of recombinant human thioredoxin-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of thioredoxin-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, recombinant human thioredoxin-1 might be a possible pharmacological strategy for severe influenza virus infection in humans. (Crit Care Med 2013; 41:171-181)No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812412012手足口病の合併症8385ENNobukoYamashitaNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5962005Virological aspects of Epstein-Barr virus infections.239246ENNobukoYamashitaHiroshiKimuraTsuneoMorishimaReview10.18926/AMO/31961<p>Epstein-Barr virus (EBV) is usually maintained in an asymptomatic and latent form by the host immune system, and primarily by EBV-specific cytotoxic T cells (CTLs). However, EBV has been linked to several refractory diseases such as EBV-associated hemophagocytic syndrome(EBV-AHS) and chronic active EBV infection (CAEBV). In these ectopic diseases, EBV infects T/NK cells, causing severe immunodeficiency with a very high EBV load. In recent years, the laboratory procedure to assess these types of EBV infections has been improved. In particular, real-time polymerase chain reaction (PCR) has been used to quantify the EBV load, and the MHC: peptide tetramer assay has been used to quantitate EBV-specific CTLs; these tests have been employed for the management of the illnesses associated with EBV infection. Here, we have reviewed the recent progress in the clinical application of these assays. The pathogenesis of EBV-infected T/NK cells, and the host immune response to infection, including the roles carried out by innate immunity and inflammatory cytokines, are likely to be revealed in the future.</p>
No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2003Analysis of linear growth in survivors of childhood acute lymphoblastic leukemiaENNobukoYamashitaNo potential conflict of interest relevant to this article was reported.