• Title/Summary/Keyword: viral neutralization

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Interleukin-18 Binding Protein (IL-18BP): A Long Journey From Discovery to Clinical Application

  • Soohyun Kim;Hyeon Yu;Tania Azam;Charles A. Dinarello
    • IMMUNE NETWORK
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    • v.24 no.1
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    • pp.1.1-1.6
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    • 2024
  • IL-18 binding protein (IL-18BP) was originally discovered in 1999 while attempting to identify an IL-18 receptor ligand binding chain (also known as IL-18Rα) by subjecting concentrated human urine to an IL-18 ligand affinity column. The IL-18 ligand chromatography purified molecule was analyzed by protein microsequencing. The result revealed a novel 40 amino acid polypeptide. To isolate the complete open reading frame (ORF), various human and mouse cDNA libraries were screened using cDNA probe derived from the novel IL-18 affinity column bound molecule. The identified entire ORF gene was thought to be an IL-18Rα gene. However, IL-18BP has been proven to be a unique soluble antagonist that shares homology with a variety of viral proteins that are distinct from the IL-18Rα and IL-18Rβ chains. The IL-18BP cDNA was used to generate recombinant IL-18BP (rIL-18BP), which was indispensable for characterizing the role of IL-18BP in vitro and in vivo. Mammalian cell lines were used to produce rIL-18BP due to its glycosylation-dependent activity of IL-18BP (approximately 20 kDa). Various forms of rIL-18BP, intact, C-terminal his-tag, and Fc fusion proteins were produced for in vitro and in vivo experiments. Data showed potent neutralization of IL-18 activity, which seems promising for clinical application in immune diseases involving IL-18. However, it was a long journey from discovery to clinical use although there have been various clinical trials since IL-18BP was discovered in 1999. This review primarily covers the discovery of IL-18BP along with how basic research influences the clinical development of IL-18BP.

Survey on Korean-native Calves Diseases and Mortality (한우 송아지의 질병발생과 폐사율 조사)

  • 강문일;한동운;정용운;정도영;이채용;이정길;위성환;조재진
    • Korean Journal of Veterinary Service
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    • v.24 no.3
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    • pp.223-241
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    • 2001
  • From September 1996 to September 1999, 419 Korean-native calves with diseases under 6-month old collected from Kyonggi, Chungcheong, Chonlla and Kyongsang were examined by clinical, microbiological, parasitic, hematologic and histopathological mean. Among them, 124 cases were tested about the neutralization antibodies against infectious bovine rhinotracheitis virus(IBRV), Parainfluenza-3 virus(PI-3V), bovine uiral diarrhea virus(BVDV), bovine ephemeral fever virus(BEFV). In calf diseases in the survey, enteric diseases(72.8%) were most frequently involved and the following orders were taken by respiratory(17.4%) and reproductive (5.0%) disorders. In the causative pathogens associated with calf diseases and motality, 48.4% was induced by bacteria origin and also 35.6% by viral agents. Calf mortality was up to 76.3% in the cae of bacterial diseases and 55.7% in viral diseases. In bacterial diseases, frequent disorders were composed of colibacillosis(52.7%), salmonellosis(13.8%), pasteurellosis(12.8%) and campylobacteriosis(3.9%) and their mortalities showed 73.8% in colibacillosis, 73.0% in pasteurellosis, 67.9% in salmonellosis and 50.0% in campylobacteriosis (50.0%). Among the outbreaks of viral diseases, there were BVD(22.8%), bovine rotavirus infection(20.8%), bovine coronavirus infection(16.8%), bovine respiratory syncytial virus infection(15.4%), IBR(15.4%). Akabane disease(4.7%) and Chuzan diseases(3.4%). Interesting results through this studies were obtained the first isolate to Chuzan virus and Ainovirus in Korea which could be promised the development for diagnostic method and vaccines soon. Calf mortality to Akabane and Chuzan diseases was 100%. Main parasitic diseases were occupied by coccidiosis and babesiosis and their mortality of babesiosis was 20.0%. Other diseases were abomasal impaction(6.7%) and toxicosis(4.5%). The mortality of abomasal impaction was 89.3%. In some causes with malformations(1.9%) were confirmed as anasarca, derodidymus, polymelia, humerus hypoplasia, and tracheal collapse. Calf diseases had mostly been occurred in one month old grout (52.5%) and its prevalence was 25.1% in two to three month old group and 22.4% in four to six month old group. In calf mortality by age, there were 37.9% in one month old group, 18.1% in two and three month old group, and 13.8% in four to six month old group, respectively. The older the age of calf, the less the prevalence of calf enteric diseases. Respiratory diseases in calves to be tested frequently occurred in one to two month old group (41.4%). In one month old calves, the prevalence of enteric disease was 80.0%(p<0.05) and that of reproductive and respiratory disease was 9.5% and 8.2%, respectively. In two month old and four to six month old, enteric disease was 65.7% and 63.8% and respiratory disease was 28.6% and 26.6%. Seasonal prevalence and mortality of Korean-native calf diseases were not a significant difference. Prevalence of calf diseases in summer(31.5%) frequently occurred to compare that in winter(20.3%). Abortion and malformation in calves frequently occurred in spring. Hematological values in 84 calves with clinical signs showed mild to marked leukocytosis. Also, there was slight increase in hematocrit, platelet, mean corpuscular volume and mean plasma volume, but all of those were included the higher level to normal ranges. Calves with respiratory signs showed slightly erythrocytosis. One hundred seventy three calves without clinical signs were not significant different to ill cases in hematological values, but number of platelets was in higher normal range. In 125 calves, 84.8% was taken the antibody to IBRV, but 72% with the antibody had recorded the titer level lower than log$_2$5. The neutralizing antibody levels of higher than $log_{2}5$ to PI-3V and BVD virus were 60.8% and 67.2% cases, respectively. There were the cases of 57.6% had the neutralizing antibody level lower than log$_2$5 to BEFV.

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Adenoviral Lower Respiratory Tract Infection of Children in Korea from 1990 Through 1998 (소아의 Adenovirus 하기도 감염증에 관한 연구 - 유행 양상과 임상 양상에 대하여 -)

  • Hong, Jung Youn;Lee, Hoan Jong
    • Pediatric Infection and Vaccine
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    • v.7 no.1
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    • pp.94-107
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    • 2000
  • Purpose : The purpose of this study is to know the clinical manifestations and the severity of adenoviral lower respiratory tract infections(LRTI) in Korean children. Methods : Adenoviral respiratory infection was diagnosed by viral culture in HEp-2 cell and indirect immunofluorescent technique with nasal aspirates. Isolated adenoviruses were typed by neutralization test. Retrospective chart review was done in patients with adenoviruses were typed by neutralization test. Retrospective chart review was done in patients with adenoviral lower respiratory tract infection, who were brought to Seoul National University Children's Hospital from November 1990 through February 1998. Results : Adenovirus was isolated in 87 cases. Of 84 cases serotyped, type 1 was recovered in 3 cases, type 2 in 13 cases, type 3 in 13, type 4 and 5 in 4 cases each other, type 6 in 1 cases, type 7 in 36 cases, type 11 in 1 case and the other types in 9 cases. Adenoviral lower respiratory infection occurred sporadically throughout the year but from November 1995 through February 1998, an outbreak of adenovirus type 7 lower respiratory infection was observed in number upto 36 case. The incidence of adenoviral infection peaked in young children between 6 months and 5 years of age and the mean age was 1 year 11 months old. There were 10 cases of mixed infection with another pathogen. Clinical diagnosis were pneumonia(88%), acute broncholitis(5.4%), acute tracheobronchitis(5.4%), croup(1.3%). The clinical features of adenoviral lower respiratory infection were severe especially in type 3 and 7 infections in aspect of fever duration, ventilator care. Extrapulmonary manifestations were gastrointestinal symptoms in 23 cases(31%), hepatomegaly in 36 cases(53%), seizure and mental alteration in 13 cases(20.3%). In chest radiographic findings, parahilar and peribronchial infiltration were in 49 cases(67%), hyperaeration in 21 cases(29%), atelectasis in 14 cases(19%), consolidation in 39 cases(53%) and bilateral pneumonic infiltration in 28 cases(38%). Among thirty six adenovirus type 7 LRTI, 15 patients(41.6%) had pleural effusion and 3 patients had chest tube insertion. Number of fetal cases related to adenovirus were 9 cases(12%) and fetal cases due to ventilatory failure were 7(11%). Conclusion : During 7 year period of studying adenoviral lower respiratory infection, we identified the serotypes of adenovirus. Among the serotypes, adenovirus type 7 were epidemically isolated. Adenovirus were isolated in severe lower respiratory infection of young children aged between 6 months and 5 years and related to death of the patients, especially when the patients had underlyng diseases or were infected by adenovirus type 7.

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Characterization of canine coronaviruses isolated from the dogs with diarrhea in Korea (설사증 이환견(犬)으로 부터 분리(分離)한 canine coronavirus의 성상(性狀)에 관한 연구(硏究))

  • Lee, Byung-hyung;Jun, Moo-hyung;Park, Jong-hyeon;Hwang, Eui-kyung;Huh, Won
    • Korean Journal of Veterinary Research
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    • v.34 no.3
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    • pp.517-527
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    • 1994
  • An attempt was made to isolate a causative viral agents from the fecal specimens of the diseased dogs with the gastroenteritis symptoms. Two coronavirus-like agents were isolated by serial dilution end point method and plaque assay. The isolates were characterized in terms of cytopathology, antigenicity, replication, physicochemical and morphological properties. The results obtained through the experiment were as follows; 1. Among 7 fecal specimens collected from the dogs with enteric disease, 2(28.6%)coronavirus-like agents showing typical cytopathic effects of canine coronavirus were isolated, and designated as CCV D1 and CCV D2, respectively. 2. By the cross-neutralization test and indirect immunofluoresence antibody test, the isolates were antigenically indentified as the standard CCV. The viruses were replicated only in the cytoplasm of A-72 cells. 3. The isolates showed no haemagglutinating activity against the erythrocytes from 11 kinds of animals. 4. The electron microscopic observation for the isolates showed spherical and pleomorphic features, covered with club-shaped projections on the surface. The size of particles was ranged from 70 to 150nm. 5. In one-step growth curve for the isolates in A-72 cells, maximum titers of intracellular vius was $10^{4.6}$ $TCID_{50}/0.1ml$ at 46 hrs postinoculation(pi) of CCV Dl and $10^{4.4}$ $TCID_{50}/0.1ml$ at 34 hrs pi of CCV D2. The maximum titers of extracellular virus was $10^{5.5}$ $TCID_{50}/0.1ml$ at 58 hrs pi of CCV D1 and $10^{5.8}$ $TCID_{50}/0.1ml$ at 46 hrs pi of CCV D2. 6. In physicochemical property test, the isolates were very sensitive to choroform and were found to be RNA virus. The viruses was stable at pH 3.0 for 1 hr and at $22{^{\circ}C}$ for 5 hrs. However, infectivity titers reduced remarkably by treatment with $56{^{\circ}C}$ for 10min.

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A Survey of Epidemic Diseases in Horses Imported into South Korea between 2003 and 2008 (2003년부터 2008년까지 한국에 수입된 말에서 전염성 질병의 실태조사)

  • Lee, Sang-Kyu;Han, Jae-Ik;Yun, Seon-Jong;Kang, Hyun-Gu
    • Journal of Veterinary Clinics
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    • v.27 no.3
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    • pp.268-272
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    • 2010
  • South Korea is susceptible to foreign diseases due to its high rate of livestock importation. The purpose of this study was to investigate the infectious conditions of contagious disease of horses imported into South Korea from other countries. The horses were tested for contagious equine metritis (CEM), equine infectious anemia (EIA), equine piroplasmosis (EP), equine viral arteritis (EVA), vesicular stomatitis (VS), dourine, and glanders. The prevalence of these infectious diseases in 6,650 horses imported from 24 countries between 2003 and 2008 was reviewed by the National Veterinary Research and Quarantine Service. Seropositive results were found for EIA, EP, EVA, dourine and glanders: 3/6,189 serum samples tested were EIA-positive, 37/6,005 samples tested by complement fixation (CF) were EP-positive, 28/6,043 samples tested by virus neutralization (VN) were EVA-positive, 4/2,071 serum samples tested by CF were positive for dourine, and 4/1,950 samples tested by CF were positive for glanders. No contagious equine metritis or vesicular stomatitis was detected. In total, 76/6,650 imported horses tested positive for an infectious disease. Notably, 4/6 sera (66.6%), all taken from horses imported from Tanzania, were positive for glanders. This is the first report of glanders infection in horses from Tanzania since 1996.

Adenoviral Lower Respiratory Tract Infections in Children; Serotypes and Clinical Characteristics (소아의 아데노바이러스 하기도 감염증: 혈청형 및 임상상)

  • Shin, Seon Hee;Lee, Hoan Jong;Yoon, Hae Sun
    • Pediatric Infection and Vaccine
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    • v.9 no.2
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    • pp.182-192
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    • 2002
  • Purpose : This study was performed to characterize the epidemiologic and clinical features of acute adenoviral lower respiratory tract infections(LRTIs). Methods : Virological analysis was done from respiratory specimens obtained from patients with LRTIs hospitalized to other hospitals and referred to the Department of Pediatrics, Seoul National University Children's Hospital(SNUCH) from June 1998 to July 2000. Viral diagnosis was made by isolation of viruses employing HEp-2 cell culture and indirect immunofluorescent staining with monoclonal antibodies. Serotypes of adenoviruses were determined by neutralization test using antiserum for types 1, 2, 3, 4, 5, 6, 7 and 11. Medical records of children admitted to the SNUCH were reviewed retrospectively. Results : Adenovirus was isolated from 118(9.0%) of 1,305 children with LRTIs. Serotypes were 3(39.0%), 7(16.9%), 1(11.0%), 2(7.6%), 4(7.6%), 6(5.9%), 11(2.5%), and 5(0.8%) and 10 strains(8.5%) were not neutralized by antisera included in the study. Infections by type 3 and type 7 occurred in outbreaks. Male to female ratio was 1.0:0.9 and mean age was 1.95 years. The clinical diagnoses were pneumonia(83%), acute tracheobronchitis(12%) and bronchiolitis(5%). Associated symptoms, signs and abnormal laboratory findings included cough(100%), sputum(73.5%), fever(54.2%), rale(59.3%), wheezing(34%), anemia(35%) and leukopenia(15.8%). Mortality was in 13.5%. Residual radiologic sequelae was identified in 32.6% of the patients followed. Conclusion : These data confirms that adenovirus may cause severe lower respiratory tract diseases, and infections by type 3 and 7 may occured in outbreaks.

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Genome Type Analysis of Adenovirus Serotypes 1, 2 and 5 Isolated from Children with Lower Respiratory Tract Infections in Korea (하기도 감염 환아에서 분리된 Adenovirus 1, 2, 5 혈청형의 유전체형 분석)

  • Park, Ki-Won;Choi, Eun-Hwa;Choun, Ji-Tae;Lee, Hoan-Jong;Park, Ki-Ho
    • Pediatric Infection and Vaccine
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    • v.12 no.2
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    • pp.166-177
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    • 2005
  • Purpose : The purpose of this study was to examine the molecular epidemiology and genetic variability of adenovirus(Ad) serotypes Ad1, Ad2, and Ad5 over 14 years in Korea. Methods : A total of 382 adenoviral strains isolated from the nasopharyngeal aspirates of children with lower respiratory tract infections in Seoul, Korea from November 1990 to February 2003 were serotyped by neutralization assay with type-specific antisera. Viral DNAs were extracted from infected cell lysates by the modified Hirt procedure. Genome type(GT) was determined by DNA restriction analysis with 12 restriction enzymess(BamHI, BclI, BglI, BglII, BstEII, EcoRI, HindIII, HpaI, SalI, SmaI, XbaI, and XhoI). To evaluate the genetic relatedness, pairwise comigrating restriction fragments(PCRF) analysis was performed. Results : Of 382 strains, 33 strains(9%) were Ad1, 45 strains(12%) were Ad2, and 24 strains(6%) were Ad5. Eighteen GTs(Ad1p1-Ad1p7, Ad1a, Ad1b, Ad1b1-Ad1b3, Ad1c, Ad1d, Ad1e, Ad1e1, Ad1e2, Ad1f) among Ad1, 24(Ad2p1-Ad2p11, Ad2a, Ad2a1-Ad2a6, Ad2b, Ad2c, Ad2d, Ad2e, Ad2e1-Ad2e3) among Ad2, and 10(Ad5p1, Ad5p2, Ad5a, Ad5a1-Ad5a7) among Ad5 strains were identified. One or two strains of the vast majority of GTs were isolated during the study period while a few GTs were identified sporadically with more than 2 strains. It is notable that some GTs such as Ad1p5 and Ad5a1 appeared in cluster during a short period. In analysis of genetic relatedness, the degree of PCRFs(pairwise comigrating restriction fragments) for Ad1 varied from 79 to 99%, for Ad2, 82 to 99%, and for Ad5, 85 to 99%. Conclusion : This study established the comprehensive nomenclature systems of Ad1, Ad2, and Ad5. Diverse GTs identified in this study have crucial implications in the genomic diversity and epidemiological characteristics of Ad1, Ad2, and Ad5.

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