• IMMUNE NETWORK
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• 제22권2호
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• pp.19.1-19.20
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• 2022

Coxsackievirus B3 (CVB3) infection causes acute pancreatitis and myocarditis. However, its pathophysiological mechanism is unclear. Here, we investigated how lipid metabolism is associated with exacerbation of CVB3 pathology using high-fat diet (HFD)-induced obese mice. Mice were intraperitoneally inoculated with 1×10⁶ pfu/mouse of CVB3 after being fed a control or HFD to induce obesity. Mice were treated with mitoquinone (MitoQ) to reduce the level of mitochondrial ROS (mtROS). In obese mice, lipotoxicity of white adipose tissue-induced inflammation caused increased replication of CVB3 and mortality. The coxsackievirus adenovirus receptor increased under obese conditions, facilitating CVB3 replication in vitro. However, lipid-treated cells with receptor-specific inhibitors did not reduce CVB3 replication. In addition, lipid treatment increased mitochondria-derived vesicle formation and the number of multivesicular bodies. Alternatively, we found that inhibition of lipid-induced mtROS decreased viral replication. Notably, HFD-fed mice were more susceptible to CVB3-induced mortality in association with increased levels of CVB3 replication in adipose tissue, which was ameliorated by administration of the mtROS inhibitor, MitoQ. These results suggest that mtROS inhibitors can be used as potential treatments for CVB3 infection.

• Pediatric Infection and Vaccine
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• 제2권2호
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• pp.200-206
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• 1995

Myocarditis refers to inflammation, necrosis, or myocytolysis that may be due to many infectious, connective tissue and many other causes affecting the myocardium or involvement of the endocardium or pericardium. The most common manifestation is congestive heart failure, although arrhythmias and sudden death may be the first sign of myocarditis. Viral myocarditis is typically a sporadic but occasionally epidemic illness, noted as an acute potentially fulminant disease of 1-to 4-wk-old infants, as an acute but more benign myopericarditis of toddlers and young children. The most common casuative agent in viral myocarditis is Coxsackievirus and the outcome of the biopsy-proven chronic dilated cardiomyopathy associated with Coxsackievirus is poor without therapy. Myocarditis may be confirmed by percutaneous endomyocardial biopsy and the viral myocarditis may be diagnosed by the serological viral study with the clinical manifestations. He was admitted for the management of tachyarrhythmias occurred suddenly without prodromal symptoms and signs and diagnosed as viral pancarditis by serological Coxsackievirus study, echocardiogram, chest x-ray, EKG and other clinical manifestations.

• 한국환경과학회지
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• 제8권2호
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• pp.165-169
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• 1999

The incidence of aseptic meningitis infection is ensuing and threatening the health of children. Enteroviruses are the major agents of aseptic meningitis and identification of virus has been a clue to diagnosis and epidemiology. The outbreak of aseptic meningitis occurred in Pusan, 1998. Patients were concentrated from April through November. Children were more susceptible than adults. Among 306 cases of specimens from stool, throat swab tested, only 7.2% were positive on virus isolation, 12 cases from stool and 10 from throat, respectively. All isolated 7 serotypes of viruses represented cytopathic effect on cultured cells. Three types of echovirus 6.25, 30 and coxsackievirus B2, B3, B4, B6 were identified by neutralizing antibody test. Isolated coxsackievirus and echovirus were observed by an electron microscope with negative staining.

• 생약학회지
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• 제47권2호
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• pp.137-142
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• 2016

Enterovirus is a common cause of several severe diseases such as myocarditis, hand-foot-mouth disease, and meningitis in children and adult. There are many try to develop new antiviral drug for direct treatment in virus infection. However, synthetic chemical antiviral drug is not working. To overcome this limitation, we examined plant extracts. The antiviral effect of plant extracts was screened by HeLa cell survival assay in coxsackievirus B3 (CVB3) infection. We observed a strong antiviral effect of Poria cocos extract in a dose-dependent manner (1 mg/ml~0.01 mg/ml). P. cocos extract (1 mg/ml) treatment was dramatically decreased virus protease 2A induced eIF4G-I cleavage and virus capsid protein VP1 production. CVB3 positive and negative strand RNA amplification were significantly reduced in P. cocos extract treatment. P. cocos extract completely blocked early time activation of ERK and AKT activity in CVB3 infection. Taken together these data indicate that the treatment of P. cocos extract strongly inhibit CVB3 replication. Poria cocos extract may possible to developed as a therapeutic agent for enterovirus.

• Journal of Microbiology and Biotechnology
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• 제33권5호
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• pp.582-590
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• 2023

Stress granules (SGs) are cytoplasmic aggregates of RNA-protein complexes that form in response to various cellular stresses and are known to restrict viral access to host translational machinery. However, the underlying molecular mechanisms of SGs during viral infections require further exploration. In this study, we evaluated the effect of SG formation on cellular responses to coxsackievirus B3 (CVB3) infection. Sodium arsenite (AS)-mediated SG formation suppressed cell death induced by tumor necrosis factor-alpha (TNF-a)/cycloheximide (CHX) treatment in HeLa cells, during which G3BP1, an essential SG component, contributed to the modulation of apoptosis pathways. SG formation in response to AS treatment blocked CVB3-mediated cell death, possibly via the reduction of mitochondrial reactive oxygen species. Furthermore, we examined whether AS treatment would affect small extracellular vesicle (sEV) formation and secretion during CVB3 infection and modulate human monocytic cell (THP-1) response. CVB3-enriched sEVs isolated from HeLa cells were able to infect and replicate THP-1 cells without causing cytotoxicity. Interestingly, sEVs from AS-treated HeLa cells inhibited CVB3 replication in THP-1 cells. These findings suggest that SG formation during CVB3 infection modulates cellular response by inhibiting the release of CVB3-enriched sEVs.

• Pediatric Infection and Vaccine
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• 제23권1호
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• pp.46-53
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• 2016

목적: 소아에서 엔테로바이러스 감염증은 무증상 감염부터 비특이적 발열성 질환, 수족구병, 수막뇌염 등 다양한 질환으로 나타날 수 있다. 본 연구는 소아 입원 환자들을 대상으로 엔테로바이러스 감염의 유전자형 별 임상양상에 대하여 알아보고자 하였다. 방법: 2014년 3월부터 2015년 3월까지 인하대병원에 입원한 환자들 중 400명을 대상으로 real-time reverse transcriptase-polymerase chain reaction (RT-PCR)로 엔테로바이러스를 검출하였으며, RT-seminested PCR로 혈청형을 분석하였다. 염기서열의 계통분석을 시행하여 neighbor-joining tree를 작성하였다. 결과: 전체 연구대상 400명 중 112명(28%)에서 엔테로바이러스 양성이 확인되었으며 엔테로바이러스 양성 환자의 평균연령은 2.66세(3일-14세), 남녀 성비는 1.73:1 이었다. 65개의 검체에서 엔테로바이러스의 혈청형을 확인할 수 있었고, coxsackievirus B5 17례(15.2%), coxsackievirus A16 13례(11.6%), enterovirus 71 10례(8.9%), coxsackievirus A2 9례(8.0%) 순이었다. 엔테로바이러스 양성 환자들 중 96명(86%)에서 비특이적 발열 증상이 있었으며, 0-11일의 다양한 발열기간을 나타냈고, 평균 발열기간은 3.13일이었다. 발진은 전체 양성환자 중 44명(39%)에서 나타났으며, 수막뇌염은 43명(38%)에서 나타났다. 염기서열에 따른 계통 분석에서 6개의 유전적 군집이 관찰되었다. 결론: 저자들은 인천지역 단일기관에 입원한 환자에서 분리된 엔테로바이러스의 혈청형과 임상양상을 확인하였다. 본 연구 결과가 앞으로 국내 엔테로바이러스 감염의 역학을 파악하는 데에 도움을 줄 것으로 생각한다.

• 대한의생명과학회지
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• 제26권4호
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• pp.302-309
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• 2020

Human Coxsackievirus B5 (HuCoxV-B5) infection has been associated with various diseases such as myocarditis, aseptic meningitis, hand-foot-and mouth-disease, and insulin-dependent diabetes. HuCoxV-B5 is a virus transmitted through the fecal-oral route and is detected in clinics, aquatic environments, food, shellfish, etc. and is one of the more important viruses in public health because of its incidence rate reported worldwide. In this study, a combination of SYBR Green-based real-time PCR primers for molecular diagnosis including monitoring of HuCoxV-B5 was selected and the optimal reaction conditions were established. Compared with the previously reported TaqMan probe-based real-time PCR method, assessments including a sample applicability test were performed. Results showed that the real-time PCR method developed in this study was suitable for a molecular diagnostic technique for detecting HuCoxV-B5. This study is expected to contribute to efforts in responding to safety accidents in public health because the proposed method facilitates rapid diagnosis of clinical patients. It can also be used as a specific monitoring tool of HuCoxV-B5 in non-clinical areas such as aquatic environments among others.

• Journal of Microbiology and Biotechnology
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• 제28권1호
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• pp.109-114
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• 2018

Coxsackievirus Type B3 (CVB3) is an enterovirus that belongs to the Picornaviridae and causes various diseases such as myocarditis and hand-foot-mouth disease. However, an effective antiviral drug is still not developed. In this study, we looked for potential inhibitors of CVB3 replication by examining the survival of CVB3-infected HeLa cells. We detected an antiviral effect by cholic acid and identified it as a candidate inhibitor of CVB3 replication. Cholic acid circulates in the liver and intestines, and it helps the digestion and absorption of lipids in the small intestine. HeLa cells were cultured in 12-well plates and treated with cholic acid (1 and $10{\mu}g/ml$) and $10^6PFU/ml$ of CVB3. After 16 h post-infection, the cells were lysed and subjected to western blot analysis and RT-PCR. The production of the viral capsid protein VP1 was dramatically decreased, and translation initiation factor eIF4G1 cleavage was significantly inhibited by treatment with $10{\mu}g/ml$ cholic acid. Moreover, cholic acid inhibited ERK signaling in CVB3-infected HeLa cells. RT-PCR showed that the amounts of the CVB3 RNA genome and mRNA for the ER stress-related transcription factor ATF4 were significantly reduced. These results showed that cholic acid strongly reduced ER stress and CVB3 proliferation. This compound can be developed as a safe natural therapeutic agent for enterovirus infections.

• Journal of Microbiology and Biotechnology
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• 제26권11호
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• pp.2012-2018
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• 2016

Coxsackievirus B3 (CVB3) is the main cause of acute myocarditis and dilated cardiomyopathy. Plant extracts are considered as useful materials to develop new antiviral drugs. We had previously selected candidate plant extracts, which showed anti-inflammatory effects. We examined the antiviral effects by using a HeLa cell survival assay. Among these extracts, we chose the Amomi Cardamomi (Amomi) extract, which showed strong antiviral effect and preserved cell survival in CVB3 infection. We investigated the mechanisms underlying the ability of Amomi extract to inhibit CVB3 infection and replication. HeLa cells were infected by CVB3 with or without Amomi extract. Erk and Akt activities, and their correlation with virus replication were observed. Live virus titers in cell supernatants and viral positive- and negative-strand RNA amplification were measured. Amomi extract significantly increased HeLa cell survival in different concentrations ($100-10{\mu}g/ml$). CVB3 capsid protein VP1 expression (76%) and viral protease 2A-induced eIF4G1 cleavage (70%) were significantly decreased in Amomi extract ($100{\mu}g/ml$) treated cells. The levels of positive- (20%) and negative-strand (80%) RNA were dramatically decreased compared with the control, as revealed by reverse transcription-PCR. In addition, Amomi extract improved mice survival (51% vs 26%) and dramatically reduced heart inflammation in a CVB3-induced myocarditis mouse model. These results suggested that Amomi extract significantly inhibited Enterovirus replication and myocarditis damage. Amomi may be developed as a therapeutic drug for Enterovirus.

• Clinical and Experimental Pediatrics
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• 제49권11호
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• pp.1186-1193
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• 2006

목 적 : 장바이러스 감염은 하절기에 소아에서 비교적 흔하게 일어나는 바이러스 감염이다. 임상증상으로 비특이적인 열, 무균성 뇌수막염, 위장관 질환, 피부 발진, 수족구병 등을 일으키며 드물게 심근염, 심외막염, 횡단성 척수염, 사지마비 등 치명적으로도 나타날 수 있다. 장바이러스 유행에 대한 보고는 있었으나, 충남지역에서 장바이러스 감염에 대한 조사 및 연구 보고는 이루어지지 않고 있었다. 이에 저자들은 2005년 5월부터 8월까지 장바이러스 감염으로 의심되어 순천향대학교 천안병원에 입원한 소아를 대상으로 역전사 중합효소연쇄반응을 이용하여 원인 바이러스를 파악하고자 본 연구를 시행하였다. 방 법 : 같은 기간 순천향대학교 천안병원 소아과에 입원한 환자 중 임상적으로 장바이러스 감염이 의심되었던 환아 157명을 대상으로 입원 후 급성기에 뇌척수액 또는 분변을 채취하여 장바이러스 세포병변효과 관찰 및 역전사 중합효소연쇄반응검사를 시행하였다. 결 과 : 연구 기간동안 장바이러스 감염이 의심되어 입원하였던 환아는 157명이었고 역전사 중합효소연쇄반응 검사에서 양성을 보인 환아는 32명(20.4%)이었다. 양성 환아 중 남자가 20명, 여자가 12명으로 남녀비는 1.67:1 이었다. 이들의 임상증상은 발열이 93.7%로 가장 많았으며 두통(90.0%), 뇌막자극증상(65.0%), 복통(30.0%) 순이었다. 분리된 장바이러스는 Echovirus 18형 17례, Coxsackievirus B5형 6례 였으며, 그 외 Echovirus 9형 2례, Coxsackievirus A6형 1례, Coxsackievirus B3형 1례 분리되었으며 유전자형이 결정되지 않은 Enterovirus가 5례였다. 결 론 : 이번 연구로 Echovirus 18형을 국내 최초로 분리하였으며, 2005년 하절기에 충남지역에서 Echovirus 18형을 포함한 여러 장바이러스 감염 원인을 알 수 있었다. 향후 장바이러스 감염 환아의 진단 및 치료를 위한 지속적인 역학적 연구가 필요할 것으로 생각된다.