2000-2002년 바이러스성 뇌수막염의 발생양상 및 특성

조경순,정명주,Jo, Gyeong-Sun,Jeong, Myeong-Ju 한국미생물학회 2003 미생물학회지 Vol.39 No.4

2000년~2002년 사이 부산지역의 병의원으로부터 의뢰된 바이러스성 뇌수막염 환자로 의심되는 환자의 가검물을 대상으로 바이러스 분리를 시도한 결과 2000년에는 검체 292건 중 2건, 2001년에는 371건 중 4건, 2002년에는 703건 중 83건의 장내바이러스를 분리하였다. 2000년에 분리된 원인 바이러스의 경우 echovirus 11 혈청형과 coxsackievirus B2 혈청형이, 2001년에는 coxsackievirus B5 혈청형만이 분리되었으며, 2002년에는 echovirus 2, 3, 6, 7, 9, 13, 25, 30 혈청형이 70건으로 가장 많았고, coxsackievirus B3과 B4 혈청형이 10건으로 예전에 비해 보다 다양한 경향을 나타내었다. 월별발생 양상은 2000년에는 동절기인 12월과 1월에, 2001년에는 5월에 집중적으로 발생하였으며, 2002년에는 4월부터 11월까지 넓은 발생 분포를 나타내었지만 특히 6월과 7월에 가장 발생율이 높았다. Echovirus와 coxsackievirus는 Vero와 HEp-2 세포주에서 강한 병변 효과를 나타내었다. 전자현미경으로 촬영한 echovirus 및 coxsackievirus의 형태학적 양상은 모두 envelope가 없고 크기가 30~35 nm로 아주 작은 구형의 특징을 나타내었다. 세포병변 효과가 나타난 세포배양액에 대하여 nested PCR을 수행한 결과 echovirus 및 coxsackievirus 모두 436 bp 위치에 단일띠를 나타내었으며, serotype은 국립보건원 소화기계바이러스과에 의뢰하여 확인 동정하였다. Enteroviruses isolation were attempted from samples obtained from aseptic meningitis-suspected patients in hospitals in Busan during 2000-2002. Enteroviruses were found in 2 of 292 cases in 2000, 4 of 371 cases in 2001, 83 of 703 cases in 2002. In 2000, the isolated viruses were found to be echovirus serotype 11 and coxsackievirus serotype B2. Coxsackievirus serotype B5 was isolated in 2001 and in 2002, echovirus serotypes 2, 3, 6, 7, 9, 13, 25, 30 were isolated in 70 cases while coxsackievirus serotypes B3 and B4 were isolated in 10 cases. Various specimens tended to emerge over the years. The occurrence in 2000 tended to be mostly focus during the cold months, December through January, while in 2001, it occurred in May. In 2002, occurrence was found to be distributed from April to November with the highest rate during June and July. The strains of Vero and HEp-2 of echovirus and coxsackievirus, respectively, are highly infectious. Electron micrograph of echovirus and coxsackievirus show that they are small nonenevolped, isometric-shaped viruses. Isolated RNA from strains of echovirus and coxsackievirus showing cytopathic effects were used to undergo nested PCR which resulted in a 436 bp single band in all the strains. The serotype was sent to the Department of Virology at the Korean National Institute of Health for identification.

1998-2000년 부산지역 소화기계 바이러스의 탐색

조경순,김영희 한국미생물학회 2001 미생물학회지 Vol.37 No.4

감염성 바이러스의 발생은 세계적인 현상으로 어린이는 물론 성인의 건강을 위협하고 있는 설정이다. 1998년-2000년 사이에 부산지역 바이러스성 전염병 유행예측사업의 과정에서 소화기계 바이러스가 탐색되었다. 의심되는 환자의 대변 및 뇌척수액, 인후가검물에서 세포배양, Latex 응집반응, 간접면역형광항체법, 전자현미경 관찰 등을 행하여 바이러스를 확인하였다. 총 검체 중에서 바이러스의 확인 율은 12.5% 이었다. 이 과정을 통하여 3 사례의 장 adenovirus 및 , 23 사례의 echovirus, 31 사례의 coxsackievirus, 36 사례의 rotavirus, 45 사례의 small round structued virus (SRSV), 7 사례의 poliovirus가 확인되었다. 확인된 주요 혈청형으로는 장 adenovirus 41형 및 echovirus 6, 9, 11, 25, 30형, coxsackievirus B2, B3, B4, B6 형 등이 탐색되었다. 각 바이러스의 월별 발생별로는 SRSV는 12월에서는 다음해 4월 사이, echovirus와 coxsackievirus는 4월에서 10월 사이에, rotavirus는 1월에서 4월사이에 각각 분리 율이 높았다. 전자현미경 관찰에서는 30-80 nm의 작은 크기의 바이러스들이 확인되었다. Incidence of infectious viruses is ensuing throughout the world and threatening the health of children as well as adults. The outbreaks of viral diseases of alimentary tract in Pusan from 1998 to 2000 were detected. Viruses were isolated from stool specimens, cerebrospinal fluid and throat swabs from suspicious patients and confirmed by cell culture, latex agglutination test, indirect immunofluorescent test and electron microscopic observation. The average isolation rate was 12.5% from the suspected specimens. From this work, 2 cases of enteric adenoviruses, 23 cases of echovirus, 31 cases of coxsackivirus 36 cases of rotavirus, 45 cases of SRSV, and 7 cases of poliovirus were detected. The major serotypes of coxsackievirus were B2, B3, B4, B6 and echovirus of serotypes 6, 9, 11, 25, and 30 were examined. Two cases of enteric adenovirus type 41 were also confirmed. The incidence of SRSV was mostly concentrated between December through following March, April through October with echovirus and coxsackievirus, and January through April with rotavirus, respectively. Electron micrograph of negative-stained viruses showed typical appearance with 30-80 nm in diameter.

Acute Viral Myopericarditis Presenting as a Transient Effusive-Constrictive Pericarditis Caused by Coinfection with Coxsackieviruses A4 and B3

이왕수,이광제,권지은,오민석,김정은,조은정,김치정 대한내과학회 2012 The Korean Journal of Internal Medicine Vol.27 No.2

Acute myopericarditis is usually caused by viral infections, and the most common cause of viral myopericarditis is coxsackieviruses. Diagnosis of myopericarditis is made based on clinical manifestations of myocardial (such as myocardial dysfunction and elevated serum cardiac enzyme levels) and pericardial (such as inflammatory pericardial effusion) involvement. Although endomyocardial biopsy is the gold standard for the confirmation of viral infection, serologic tests can be helpful. Conservative management is the mainstay of treatment in acute myopericarditis. We report here a case of a 24-year-old man with acute myopericarditis who presented with transient effusive-constrictive pericarditis. Echocardiography showed transient pericardial effusion with constrictive physiology and global regional wall motion abnormalities of the left ventricle. The patient also had an elevated serum troponin I level. A computed tomogram of the chest showed pericardial and pleural effusion, which resolved after 2 weeks of supportive treatment. Serologic testing revealed coxsackievirus A4 and B3 coinfection. The patient received conservative medical treatment, including nonsteroidal anti-inflammatory drugs, and he recovered completely with no complications. Acute myopericarditis is usually caused by viral infections, and the most common cause of viral myopericarditis is coxsackieviruses. Diagnosis of myopericarditis is made based on clinical manifestations of myocardial (such as myocardial dysfunction and elevated serum cardiac enzyme levels) and pericardial (such as inflammatory pericardial effusion) involvement. Although endomyocardial biopsy is the gold standard for the confirmation of viral infection, serologic tests can be helpful. Conservative management is the mainstay of treatment in acute myopericarditis. We report here a case of a 24-year-old man with acute myopericarditis who presented with transient effusive-constrictive pericarditis. Echocardiography showed transient pericardial effusion with constrictive physiology and global regional wall motion abnormalities of the left ventricle. The patient also had an elevated serum troponin I level. A computed tomogram of the chest showed pericardial and pleural effusion, which resolved after 2 weeks of supportive treatment. Serologic testing revealed coxsackievirus A4 and B3 coinfection. The patient received conservative medical treatment, including nonsteroidal anti-inflammatory drugs, and he recovered completely with no complications.

Acute Viral Myopericarditis presenting as a transient Effusive-Constrictive Pericarditis Caused by Coinfection with coxsackieviruses a4 and B3

( Wang Soo Lee ),( Kwang Je Lee ),( Jee Eun Kwon ),( Min Seok Oh ),( Jeong Eun Kim ),( Eun Jung Cho ),( Chee Jeong Kim ) 대한내과학회 2012 The Korean Journal of Internal Medicine Vol.27 No.2

Acute myopericarditis is usually caused by viral infections, and the most common cause of viral myopericarditis is coxsackieviruses. Diagnosis of myopericarditis is made based on clinical manifestations of myocardial (such as myocardial dysfunction and elevated serum cardiac enzyme levels) and pericardial (such as inflammatory pericardial effusion) involvement. Although endomyocardial biopsy is the gold standard for the confirmation of viral infection, serologic tests can be helpful. Conservative management is the mainstay of treatment in acute myopericarditis. We report here a case of a 24-year-old man with acute myopericarditis who presented with transient effusive-constrictive pericarditis. Echocardiography showed transient pericardial effusion with constrictive physiology and global regional wall motion abnormalities of the left ventricle. The patient also had an elevated serum troponin I level. A computed tomogram of the chest showed pericardial and pleural effusion, which resolved after 2 weeks of supportive treatment, Serologic testing revealed coxsackievirus A4 and B3 coinfection. The patient received conservative medical treatment, including nonsteroidal anti-inflammatory drugs, and he recovered completely with no complications.

Fructus Amomi Cardamomi Extract Inhibits Coxsackievirus-B3 Induced Myocarditis in a Murine Myocarditis Model

( Yun-gyeong Lee ),( Jung-ho Park ),( Eun-seok Jeon ),( Jin-hee Kim ),( Byung-kwan Lim ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.11

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 ㎍/ml). CVB3 capsid protein VP1 expression (76%) and viral protease 2A-induced eIF4G1 cleavage (70%) were significantly decreased in Amomi extract (100 ㎍/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.

오리방풀로부터 분리된 ORI2의 췌장염 유발 콕사키바이러스B4 증식억제

임병관,조소연,김진희 한국생약학회 2014 생약학회지 Vol.45 No.4

The ORI2 (3-[3,4-dihydroxyphenyl]acrylic acid 1-[3,4-dihydroxyphenyl]-2-methoxycarbonylethyl ester) was purified from the extract of Isodon excisus. We confirmed the antiviral effect of ORI2 in a coxsackievirus-induced pancreatitis model. Coxsackievirus B4 (CVB4) is a common cause of pancreatitis and may be reason of the type-1 diabetes. Anti-enteroviral compounds were screened by HeLa cell survival assay. Purified natural compounds were added to HeLa cells cultured 96-well plates after 104 PFU/ml CVB4 pre-incubation for 30 min. ORI2 significantly improved HeLa cell survival in a dose-dependent manner. In addition, ORI2 (1 mM) treatment was dramatically decreased virus protease 2A induced eIF4G-I cleavage and viral VP1 capsid protein production. HeLa cell virus titers and viral RNA replication were significantly decreased in ORI2-treatment in a dose dependent manner (1 mM~0.001 mM). These results demonstrate that ORI2 has a strong antiviral effect. It was significantly decreased virus replication. ORI2 may be developed as a potential therapeutic agent for CVB4.

Cholic Acid Attenuates ER Stress-Induced Cell Death in Coxsackievirus-B3 Infection

( Jae-young Han ),( Hae In Jeong ),( Cheol-woo Park ),( Jisoo Yoon ),( Jaeyoung Ko ),( Sang-jip Nam ),( Byung-kwan Lim ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.1

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 μg/ml) and 10⁶ PFU/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 μg/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.

장바이러스 71에 의한 수족구병

김종현,김성준,천두성 대한의사협회 2009 대한의사협회지 Vol.52 No.9

Hand -foot- mouth disease (HFMD), one of the more distinctive rash syndromes, is most frequently caused by coxsackievirus A16, but can also be caused by enterovirus 71 (EV71) and other coxsackieviruses. Recently, there have been large outbreaks of simple, neurologically complicated and even fatal HFMD caused by EV71 in Western Pacific Area. However, in the Republic of Korea, despite its location in EV71 endemic Western Pacific Area, published reports on HFMD with EV71 are rare and there are no published reports on fatal cases. After the first fatal case of HFMD caused by EV71 announced in May 2009, much more cases of neurologically complicated HFMD have been announced. Even now, physician’s increased awareness about the seriousness of HFMD, viral surveillance and early warning system of HFMD, and early detection and proper management of potentially life threatening HFMD caused by EV71 are required in the Republic of Korea, as in the neighboring countries.

1997년 경상남도 중부지방에서 유행한 무균성 뇌막염의 임상적 고찰

박선영,권오수,김원엽,정원조,마상혁,김상기,남성진,조성래,구본천,이규만,Park, Sun Young,Kwon, Oh Su,Kim, Won Youb,Jung, Won Jo,Ma, Sang Hyouk,Kim, Sang Ki,Nam, Sung Jin,Jo, Sung Rae,Gu, Bon Chun,Lee, Kyu Man 대한소아감염학회 1998 Pediatric Infection and Vaccine Vol.5 No.1

목 적 : 장바이러스는 무균성 뇌막염의 가장 흔한 원인으로 알려져 있으며 1993년과 1996년에 국내에서 유행하였던 무균성 뇌막염은 주로 echovirus type 9에 의한 것이었다. 무균성 뇌막염의 유행시 원인 바이러스를 밝혀내는 일은 진단뿐 아니라 역학적인 의미에서도 필요하다. 이에 저자들은 1997년도에 마산 지역을 포함하는 경상남도 중부지역에서 유행하였던 무균성 뇌막염 환자를 대상으로 원인 바이러스를 규명하고 임상증상과의 관계를 추구하고자 본 연구를 시행하였다. 방 법 : 1997년 3월부터 10월까지 마산 파티마병원에 무균성 뇌막염으로 진단된 환자 239명(소아 213명, 성인 26명)에서 채취한 검체(뇌척수액 128례, 대변 239례)를 대상으로 바이러스 배양과 enterovirus RNA 검출을 시행하였다. 배양된 바이러스는 면역형광법을 이용하여 동정하였고 장바이러스 RNA는 reverse transcription-polymerase chain reaction(RT-PCR)을 이용하여 확인하였다. 결 과 : 1) 환자의 발생시기는 3월부터 10월까지였으며 6월에 가장 많은 환자의 분포를 보였다. 2) 대상 환자 239명(소아과 213명, 내과 26명)의 연령별 분포를 보면 소아환자의 평균연령은 4.9세로 신생아에서부터 15세에 이르기까지 다양하게 분포하였고 16세이상 내과 병동에 입원하였던 환자는 평균 연령이 24.2세로 16세에서 35세까지의 연령 분포를 보였다. 3) 환자에서 바이러스 분리는 뇌척수액 128례중 53례(41.4%), 대변에서는 239례중 163례(68.2%)에서 분리가 되었다. 4) 분리된 바이러스의 결과를 보면 뇌척수액에서는 echovirus type30이 16례(30.2%), echovirus type 6이 6례(11.3%), echovirus type 4가 1례, 아형이 결정되지 않은 echovirus가 4례, coxsackievirus type B5가 1례, 아형이 결정되지 않은 enterovirus가 24례 이었다. 한편 대변에서는 echovirus type30이 72례(44.2%), echovirus type 6이 21례(12.9%), echovirus type 4가 1례, 아형이 결정되지 않은 echovirus가 17례(10.4%), coxsackievirus type B5가 1례, A24가 2례, 아형이 결정되지 않은 coxsackievirus type B가 3례, 아형이 결정되지 않은 enterovirus가 46례였다. 결 론 : 1997년 3월부터 10월까지 경상남도 중부지방에서 무균성 뇌막염의 유행이 있었으며 원인 바이러스는 echovirus type 30이 주된 원인 바이러스이었고 그 외에 echovirus type 4, 6, coxsackievirus B5, coxsackievirus A24에 의한 무균성 뇌막염의 산발적인 발생이 있었다. Purpose : Enteroviruses are the most common cause of aseptic meningitis. The epidemics of aseptic meningitis in 1993 and 1996 were mostly caused by echovirus type 9. Identification of the causative virus of aseptic meningitis in epidemics, is very important not only for diagnosis but also for epidemiologic purpose. The purpose of this study was to identify the causative virus and investigate the relationship between aseptic meningitis, prevailed in Masan and surrounding areas in Kyoungsangnamdo in 1997, and its clinical manifestations. Methods : One hundred twenty eight cerebrospinal fluid(CSF) and 239 stool specimens were obtained from 239 patients(213 children and 26 adult patients) with aseptic meningitis were admitted to Masan Fatima Hospitals from March to October 1997. Viral isolation and serotype identification was performed by cell culture and immunofluorescent test. Enteroviruses not typed by immunofluorescent test was confirmed by reverse transcription-polymerase chain reaction(RT-PCR). Results : 1) The peak incidence was noted in June. 2) The age of 239 patients(pediatrics-213 cases, internal medicine-26 cases) that were diagnosed ranged from neonate to 35 years, the age of the patients of pediatrics ranged from neonate to 15years(mean 4.9 years), the age of the patients of internal medicine (above 16 years) ranged from 16 years to 35 years(mean 24.2 years). 3) Fifty-three(41.4%) of 128 CSF specimens were positive for enteroviruses, and 163(68.2%) of 239 stool specimens were positive for enteroviruses respectively. 4) Serotypes of 53 enteroviruses isolated from CSF were 16(30.2%) of echovirus type 30, 6(11.3%) of echovirus type 6, 1 of echovirus type 4, 4 of untyped echovirus, 1 of coxsackievirus type B5, and 24 isolates of untyped enteroviruses. Of 163 enterovirus isolated from stool were 72(44.2%) of echovirus type 30, 21(12.9%) of echovirus type 6, 1 of echovirus type 4, 17(10.4%) of undetermined subtyped echovirus, 1 of coxsackievirus type B5, 2 of A24, 3 of undetermined subtyped coxsackievirus type B, and 46 isolates of untyped enterovirus. Conclusion : There were epidemics of aseptic meningitis in the central areas of Kyoungsangnamdo from March to October 1997. The main causative organism was thought to be the echovirus type 30, and echovirus type 4, 6, coxsackievirus B5 and A24 were also thought to contribute to the epidemics.

국내 감염성질환 병원체의 성상분석을 통한 표준실험실 체계 구축(Ⅱ) : 장내바이러스와 B형간염바이러스 국내 분리주의 성상분석(1)

윤재득,지영미,김기순,천두성,안정배,정윤석,신수연,이선화,이지원,조해월 국립보건연구원 2000 국립보건원보 Vol.37 No.-