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Sami Oikarinen - One of the best experts on this subject based on the ideXlab platform.
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Coxsackievirus B1 infections are associated with the initiation of insulin driven autoimmunity that progresses to type 1 diabetes
Diabetologia, 2018Co-Authors: Amirbabak Sioofykhojine, Olli H Laitinen, Outi Pakkanen, Sami Oikarinen, Minna M Hankaniemi, Heini Huhtala, Tanja Ruokoranta, Jussi Lehtonen, Noora Nurminen, Jorma ToppariAbstract:Islet autoimmunity usually starts with the appearance of autoantibodies against either insulin (IAA) or GAD65 (GADA). This categorises children with preclinical type 1 diabetes into two immune phenotypes, which differ in their genetic background and may have different aetiology. The aim was to study whether Coxsackievirus group B (CVB) infections, which have been linked to the initiation of islet autoimmunity, are associated with either of these two phenotypes in children with HLA-conferred susceptibility to type 1 diabetes. All samples were from children in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study. Individuals are recruited to the DIPP study from the general population of new-born infants who carry defined HLA genotypes associated with susceptibility to type 1 diabetes. Our study cohort included 91 children who developed IAA and 78 children who developed GADA as their first appearing single autoantibody and remained persistently seropositive for islet autoantibodies, along with 181 and 151 individually matched autoantibody negative control children, respectively. Seroconversion to positivity for neutralising antibodies was detected as the surrogate marker of CVB infections in serial follow-up serum samples collected before and at the appearance of islet autoantibodies in each individual. CVB1 infections were associated with the appearance of IAA as the first autoantibody (OR 2.4 [95% CI 1.4, 4.2], corrected p = 0.018). CVB5 infection also tended to be associated with the appearance of IAA, however, this did not reach statistical significance (OR 2.3, [0.7, 7.5], p = 0.163); no other CVB types were associated with increased risk of IAA. Children who had signs of a CVB1 infection either alone or prior to infections by other CVBs were at the highest risk for developing IAA (OR 5.3 [95% CI 2.4, 11.7], p < 0.001). None of the CVBs were associated with the appearance of GADA. CVB1 infections may contribute to the initiation of islet autoimmunity being particularly important in the insulin-driven autoimmune process.
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relative sensitivity of immunohistochemistry multiple reaction monitoring mass spectrometry in situ hybridization and pcr to detect Coxsackievirus B1 in a549 cells
Journal of Clinical Virology, 2016Co-Authors: Jutta E Laiho, Sami Oikarinen, Maarit Oikarinen, Sarah J Richardson, Gun Frisk, Julius O Nyalwidhe, Tanya C Burch, Margaret A Morris, Alberto Pugliese, Francesco DottaAbstract:Abstract Background Enteroviruses (EVs) have been linked to the pathogenesis of several diseases and there is a collective need to develop improved methods for the detection of these viruses in tissue samples. Objectives This study evaluates the relative sensitivity of immunohistochemistry (IHC), proteomics, in situ hybridization (ISH) and RT-PCR to detect one common EV, Coxsackievirus B1 (CVB1), in acutely infected human A549 cells in vitro . Study design A549 cells were infected with CVB1 and diluted with uninfected A549 cells to produce a limited dilution series in which the proportion of infected cells ranged from 10 −1 to 10 −8 . Analyses were carried out by several laboratories using IHC with different anti-EV antibodies, ISH with both ViewRNA and RNAScope systems, liquid chromatography multiple reaction monitoring mass spectrometry (LC/MRM/MS/MS), and two modifications of RT-PCR. Results RT-PCR was the most sensitive method for EV detection yielding positive signals in the most diluted sample (10 −8 ). LC/MRM/MS/MS detected viral peptides at dilutions as high as 10 −7 . The sensitivity of IHC depended on the antibody used, and the most sensitive antibody (Dako clone 5D8/1) detected virus proteins at a dilution of 10 −6 , while ISH detected the virus at dilutions of 10 −4 . Conclusions All methods were able to detect CVB1 in infected A549 cells. RT-PCR was most sensitive followed by LC/MRM/MS/MS and then IHC. The results from this in vitro survey suggest that all methods are suitable tools for EV detection but that their differential sensitivities need to be considered when interpreting the results from such studies.
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application of bioinformatics in probe design enables detection of enteroviruses on different taxonomic levels by advanced in situ hybridization technology
Journal of Clinical Virology, 2015Co-Authors: Jutta E Laiho, Didier Hober, Sami Oikarinen, Maarit Oikarinen, Virginia M. Stone, Par G Larsson, Steven M Oberste, Malin Flodstromtullberg, Jorma Isola, Heikki HyotyAbstract:Abstract Background Enteroviral infections are common, affecting humans across all age groups. RT-PCR is widely used to detect these viruses in clinical samples. However, there is a need for sensitive and specific in situ detection methods for formalin-fixed tissues, allowing for the anatomical localization of the virus and identification of its serotype. Objectives The aim was to design novel enterovirus probes, assess the impact of probe design for the detection and optimize the new single molecule in situ hybridization technology for the detection of enteroviruses in formalin-fixed paraffin-embedded samples. Study design Four enterovirus RNA-targeted oligonucleotide RNA probes – two probes for wide range enterovirus detection and two for serotype-targeted detection of Coxsackievirus B1 (CVB1) – were designed and validated for the commercially available QuantiGene ViewRNA in situ hybridization method. The probe specificities were tested using a panel of cell lines infected with different enterovirus serotypes and CVB infected mouse pancreata. Results The two widely reactive probe sets recognized 19 and 20 of the 20 enterovirus serotypes tested, as well as 27 and 31 of the 31 CVB1 strains tested. The two CVB1 specific probe sets detected 30 and 14 of the 31 CVB1 strains, with only minor cross-reactivity to other serotypes. Similar results were observed in stained tissues from CVB –infected mice. Conclusions These novel in-house designed probe sets enable the detection of enteroviruses from formalin-fixed tissue samples. Optimization of probe sequences makes it possible to tailor the assay for the detection of enteroviruses on the serotype or species level.
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Coxsackievirus B1 is associated with induction of β cell autoimmunity that portends type 1 diabetes
Diabetes, 2014Co-Authors: Olli H Laitinen, Hanna Honkanen, Outi Pakkanen, Sami Oikarinen, Minna M Hankaniemi, Heini Huhtala, Tanja Ruokoranta, Valerie Lecouturier, Philippe Andre, Raimo HarjuAbstract:The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes that could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study. The study participants comprised 183 case children testing persistently positive for at least two diabetespredictive autoantibodies and 366 autoantibodynegative matched control children. Coxsackievirus B1 was associated with an increased risk of b-cell autoimmunity. This risk was strongest when infection occurred a few months before autoantibodies appeared and was attenuated by the presence of maternal antibodies against the virus. Two other Coxsackieviruses, B3 and B6, were associated with a reduced risk, with an interaction pattern, suggesting immunological cross-protection against Coxsackievirus B1. These results support previous observations suggesting that the group B Coxsackieviruses are associated with the risk of type 1 diabetes. The clustering of the risk and protective viruses to this narrow phylogenetic lineage supports the biological plausibility of this phenomenon.
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virus antibody survey in different european populations indicates risk association between Coxsackievirus B1 and type 1 diabetes
Diabetes, 2014Co-Authors: Sami Oikarinen, Didier Hober, Sisko Tauriainen, Bernadette Lucas, Andriani Vazeou, Amirbabak Sioofykhojine, Evangelos Bozas, Peter Muir, Hanna HonkanenAbstract:Enteroviruses (EVs) have been connected to type 1 diabetes in various studies. The current study evaluates the association between specific EV subtypes and type 1 diabetes by measuring type-specific antibodies against the group B Coxsackieviruses (CVBs), which have been linked to diabetes in previous surveys. Altogether, 249 children with newly diagnosed type 1 diabetes and 249 control children matched according to sampling time, sex, age, and country were recruited in Finland, Sweden, England, France, and Greece between 2001 and 2005 (mean age 9 years; 55% male). Antibodies against CVB1 were more frequent among diabetic children than among control children (odds ratio 1.7 [95% CI 1.0-2.9]), whereas other CVB types did not differ between the groups. CVB1-associated risk was not related to HLA genotype, age, or sex. Finnish children had a lower frequency of CVB antibodies than children in other countries. The results support previous studies that suggested an association between CVBs and type 1 diabetes, highlighting the possible role of CVB1 as a diabetogenic virus type.
Jutta E Laiho - One of the best experts on this subject based on the ideXlab platform.
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A novel rat CVB1-VP1 monoclonal antibody 3A6 detects a broad range of enteroviruses
Scientific Reports, 2018Co-Authors: Niila V. V. Saarinen, Jutta E Laiho, Sarah J Richardson, Marie Zeissler, Virginia M. Stone, Varpu Marjomäki, Tino Kantoluoto, Marc S. Horwitz, Amirbabak Sioofy-khojine, Anni HonkimaaAbstract:Enteroviruses ( EVs ) are common RNA viruses that cause diseases ranging from rash to paralytic poliomyelitis. For example, EV-A and EV-C viruses cause hand-foot and mouth disease and EV-B viruses cause encephalitis and myocarditis, which can result in severe morbidity and mortality. While new vaccines and treatments for EVs are under development, methods for studying and diagnosing EV infections are still limited and therefore new diagnostic tools are required. Our aim was to produce and characterize new antibodies that work in multiple applications and detect EVs in tissues and in vitro . Rats were immunized with Coxsackievirus B1 capsid protein VP1 and hybridomas were produced. Hybridoma clones were selected based on their reactivity in different immunoassays. The most promising clone, 3A6, was characterized and it performed well in multiple techniques including ELISA, immunoelectron microscopy, immunocyto- and histochemistry and in Western blotting, detecting EVs in infected cells and tissues. It recognized several EV-Bs and also the EV-C representative Poliovirus 3, making it a broad-spectrum EV specific antibody. The 3A6 rat monoclonal antibody can help to overcome some of the challenges faced with commonly used EV antibodies: it enables simultaneous use of mouse-derived antibodies in double staining and it is useful in murine models.
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relative sensitivity of immunohistochemistry multiple reaction monitoring mass spectrometry in situ hybridization and pcr to detect Coxsackievirus B1 in a549 cells
Journal of Clinical Virology, 2016Co-Authors: Jutta E Laiho, Sami Oikarinen, Maarit Oikarinen, Sarah J Richardson, Gun Frisk, Julius O Nyalwidhe, Tanya C Burch, Margaret A Morris, Alberto Pugliese, Francesco DottaAbstract:Abstract Background Enteroviruses (EVs) have been linked to the pathogenesis of several diseases and there is a collective need to develop improved methods for the detection of these viruses in tissue samples. Objectives This study evaluates the relative sensitivity of immunohistochemistry (IHC), proteomics, in situ hybridization (ISH) and RT-PCR to detect one common EV, Coxsackievirus B1 (CVB1), in acutely infected human A549 cells in vitro . Study design A549 cells were infected with CVB1 and diluted with uninfected A549 cells to produce a limited dilution series in which the proportion of infected cells ranged from 10 −1 to 10 −8 . Analyses were carried out by several laboratories using IHC with different anti-EV antibodies, ISH with both ViewRNA and RNAScope systems, liquid chromatography multiple reaction monitoring mass spectrometry (LC/MRM/MS/MS), and two modifications of RT-PCR. Results RT-PCR was the most sensitive method for EV detection yielding positive signals in the most diluted sample (10 −8 ). LC/MRM/MS/MS detected viral peptides at dilutions as high as 10 −7 . The sensitivity of IHC depended on the antibody used, and the most sensitive antibody (Dako clone 5D8/1) detected virus proteins at a dilution of 10 −6 , while ISH detected the virus at dilutions of 10 −4 . Conclusions All methods were able to detect CVB1 in infected A549 cells. RT-PCR was most sensitive followed by LC/MRM/MS/MS and then IHC. The results from this in vitro survey suggest that all methods are suitable tools for EV detection but that their differential sensitivities need to be considered when interpreting the results from such studies.
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application of bioinformatics in probe design enables detection of enteroviruses on different taxonomic levels by advanced in situ hybridization technology
Journal of Clinical Virology, 2015Co-Authors: Jutta E Laiho, Didier Hober, Sami Oikarinen, Maarit Oikarinen, Virginia M. Stone, Par G Larsson, Steven M Oberste, Malin Flodstromtullberg, Jorma Isola, Heikki HyotyAbstract:Abstract Background Enteroviral infections are common, affecting humans across all age groups. RT-PCR is widely used to detect these viruses in clinical samples. However, there is a need for sensitive and specific in situ detection methods for formalin-fixed tissues, allowing for the anatomical localization of the virus and identification of its serotype. Objectives The aim was to design novel enterovirus probes, assess the impact of probe design for the detection and optimize the new single molecule in situ hybridization technology for the detection of enteroviruses in formalin-fixed paraffin-embedded samples. Study design Four enterovirus RNA-targeted oligonucleotide RNA probes – two probes for wide range enterovirus detection and two for serotype-targeted detection of Coxsackievirus B1 (CVB1) – were designed and validated for the commercially available QuantiGene ViewRNA in situ hybridization method. The probe specificities were tested using a panel of cell lines infected with different enterovirus serotypes and CVB infected mouse pancreata. Results The two widely reactive probe sets recognized 19 and 20 of the 20 enterovirus serotypes tested, as well as 27 and 31 of the 31 CVB1 strains tested. The two CVB1 specific probe sets detected 30 and 14 of the 31 CVB1 strains, with only minor cross-reactivity to other serotypes. Similar results were observed in stained tissues from CVB –infected mice. Conclusions These novel in-house designed probe sets enable the detection of enteroviruses from formalin-fixed tissue samples. Optimization of probe sequences makes it possible to tailor the assay for the detection of enteroviruses on the serotype or species level.
Doo-sung Cheon - One of the best experts on this subject based on the ideXlab platform.
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epidemics of viral meningitis caused by echovirus 6 and 30 in korea in 2008
Virology Journal, 2012Co-Authors: Hye-jin Kim, Seoyeon Hwang, Byounghak Kang, Jiyoung Hong, Kisang Kim, Doo-sung CheonAbstract:Enteroviruses (EVs) are the leading cause of aseptic meningitis, which is the most frequent central nervous system infection worldwide. We aimed to characterize the EVs involved in an aseptic meningitis outbreak in Korea in 2008. In Korea, Echovirus type 30 (E30) and E6 have been associated with outbreaks and frequent meningitis. During 2008, through nationwide surveillance, we collected specimens from 758 patients with aseptic meningitis-related clinical manifestations. The detection of EVs from specimens was subjected to a diagnostic real-time RT-PCR in the 5' NCR. A semi-nested polymerase chain reaction (PCR) to amplify sequences from the VP1 region and sequence comparison with reference strains registered in Genbank was performed for the genotype determination. Most patients (98%) in this outbreak were children < 15 years of age. The temporal distribution of the E6 and E30 epidemics showed an obvious seasonal pattern during the short period from June to July. A large majority of the EV-positive patients experienced fever, headache, vomiting, and neck stiffness. Some patients also showed cold symptoms, sore throat, altered mental status, and seizures. We did not observe a higher fatality rate in children with E6 or E30 infection. Most of the patients recovered uneventfully. In most cases, the cerebrospinal fluid (CSF) profile was studied, and generally showed a higher than normal white blood cell count (≥ 5/mm3). We detected EVs from 513 patients (67.68%) and identified the EV genotype in 287 patients. E30 (n = 155, 50.4%) and E6 (n = 95, 33.1%) were the predominant genotypes. E9, E1, E7, E16, Coxsackievirus A3, 4, 6, Coxsackievirus B1, 3, and 10 were also identified. According to phylogenetic analysis, E30 belonged to subgroup 4b, and E6, to the C4 subgroup. Conclusively, aseptic meningitis was the most common manifestation in children with either echovirus 30 or 6 infection. Identification of E6 and E30 as the prominent EVs in the 2008 outbreak in South Korea shows the potential of EVs to cause a serious disease in an unpredictable (fashion. Our findings provide new) insights into the clinical and virological features of the aseptic meningitis outbreak caused by E30 and E6.
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Epidemics of viral meningitis caused by echovirus 6 and 30 in Korea in 2008
Virology Journal, 2012Co-Authors: Hye-jin Kim, Seoyeon Hwang, Byounghak Kang, Jiyoung Hong, Kisang Kim, Doo-sung CheonAbstract:Background Enteroviruses (EVs) are the leading cause of aseptic meningitis, which is the most frequent central nervous system infection worldwide. We aimed to characterize the EVs involved in an aseptic meningitis outbreak in Korea in 2008. In Korea, Echovirus type 30 (E30) and E6 have been associated with outbreaks and frequent meningitis. Methods During 2008, through nationwide surveillance, we collected specimens from 758 patients with aseptic meningitis-related clinical manifestations. The detection of EVs from specimens was subjected to a diagnostic real-time RT-PCR in the 5' NCR. A semi-nested polymerase chain reaction (PCR) to amplify sequences from the VP1 region and sequence comparison with reference strains registered in Genbank was performed for the genotype determination. Results Most patients (98%) in this outbreak were children < 15 years of age. The temporal distribution of the E6 and E30 epidemics showed an obvious seasonal pattern during the short period from June to July. A large majority of the EV-positive patients experienced fever, headache, vomiting, and neck stiffness. Some patients also showed cold symptoms, sore throat, altered mental status, and seizures. We did not observe a higher fatality rate in children with E6 or E30 infection. Most of the patients recovered uneventfully. In most cases, the cerebrospinal fluid (CSF) profile was studied, and generally showed a higher than normal white blood cell count (≥ 5/mm^3). We detected EVs from 513 patients (67.68%) and identified the EV genotype in 287 patients. E30 (n = 155, 50.4%) and E6 (n = 95, 33.1%) were the predominant genotypes. E9, E1, E7, E16, Coxsackievirus A3, 4, 6, Coxsackievirus B1, 3, and 10 were also identified. According to phylogenetic analysis, E30 belonged to subgroup 4b, and E6, to the C4 subgroup. Conclusions Conclusively, aseptic meningitis was the most common manifestation in children with either echovirus 30 or 6 infection. Identification of E6 and E30 as the prominent EVs in the 2008 outbreak in South Korea shows the potential of EVs to cause a serious disease in an unpredictable (fashion. Our findings provide new) insights into the clinical and virological features of the aseptic meningitis outbreak caused by E30 and E6.
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Epidemics of enterovirus infection in Chungnam Korea, 2008 and 2009
Virology Journal, 2011Co-Authors: Kyoungah Baek, Kwisung Park, Jeesuk Yu, Insoo Rheem, Seoyeon Hwang, Doo-sung Cheon, Jaehyoung Song, Youngjin Choi, Joonsoo ParkAbstract:Previously, we explored the epidemic pattern and molecular characterization of enteroviruses isolated in Chungnam, Korea from 2005 to 2006. The present study extended these observations to 2008 and 2009. In this study, enteroviruses showed similar seasonal prevalent pattern from summer to fall and age distribution to previous investigation. The most prevalent month was July: 42.9% in 2008 and 31.9% in 2009. The highest rate of enterovirus-positive samples occurred in children < 1-year-old-age. Enterovirus-positive samples were subjected to sequence determination of the VP1 region, which resolved the isolated enteroviruses into 10 types in 2008 (Coxsackievirus A4, A16, B1, B3, echovirus 6, 7, 9, 11, 16, and 30) and 8 types in 2009 (Coxsackievirus A2, A4, A5, A16, B1, B5, echovirus 11, and enterovirus 71). The most prevalent enterovirus serotype in 2008 and 2009 was echovirus 30 and Coxsackievirus B1, respectively, whereas echovirus 18 and echovirus 5 were the most prevalent types in 2005 and 2006, respectively. Comparison of Coxsackievirus B1 and B5 of prevalent enterovirus type in Korea in 2009 with reference strains of each same serotype were conducted to genetic analysis by a phylogenetic tree. The sequences of Coxsackievirus B1 strains segregated into four distinct clusters (A, B, C, and D) with some temporal and regional sub-clustering. Most of Korean Coxsackievirus B1 strains in 2008 and 2009 were in cluster D, while only "Kor08-CVB1-001CN" was cluster C. The Coxsackievirus B5 strains segregated in five distinct genetic groups (clusters A-E) were supported by high bootstrap values. The Korean strains isolated in 2001 belonged to cluster D, whereas Korean strains isolated in 2005 and 2009 belonged to cluster E. Comparison of the VP1 amino acid sequences of the Korean Coxsackievirus B5 isolates with reference strains revealed amino acid sequence substitutions at nine amino acid sequences (532, 562, 570, 571, 576-578, 582, 583, and 585).
Anni Honkimaa - One of the best experts on this subject based on the ideXlab platform.
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A novel rat CVB1-VP1 monoclonal antibody 3A6 detects a broad range of enteroviruses
Scientific Reports, 2018Co-Authors: Niila V. V. Saarinen, Jutta E Laiho, Sarah J Richardson, Marie Zeissler, Virginia M. Stone, Varpu Marjomäki, Tino Kantoluoto, Marc S. Horwitz, Amirbabak Sioofy-khojine, Anni HonkimaaAbstract:Enteroviruses ( EVs ) are common RNA viruses that cause diseases ranging from rash to paralytic poliomyelitis. For example, EV-A and EV-C viruses cause hand-foot and mouth disease and EV-B viruses cause encephalitis and myocarditis, which can result in severe morbidity and mortality. While new vaccines and treatments for EVs are under development, methods for studying and diagnosing EV infections are still limited and therefore new diagnostic tools are required. Our aim was to produce and characterize new antibodies that work in multiple applications and detect EVs in tissues and in vitro . Rats were immunized with Coxsackievirus B1 capsid protein VP1 and hybridomas were produced. Hybridoma clones were selected based on their reactivity in different immunoassays. The most promising clone, 3A6, was characterized and it performed well in multiple techniques including ELISA, immunoelectron microscopy, immunocyto- and histochemistry and in Western blotting, detecting EVs in infected cells and tissues. It recognized several EV-Bs and also the EV-C representative Poliovirus 3, making it a broad-spectrum EV specific antibody. The 3A6 rat monoclonal antibody can help to overcome some of the challenges faced with commonly used EV antibodies: it enables simultaneous use of mouse-derived antibodies in double staining and it is useful in murine models.
Seoyeon Hwang - One of the best experts on this subject based on the ideXlab platform.
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epidemics of viral meningitis caused by echovirus 6 and 30 in korea in 2008
Virology Journal, 2012Co-Authors: Hye-jin Kim, Seoyeon Hwang, Byounghak Kang, Jiyoung Hong, Kisang Kim, Doo-sung CheonAbstract:Enteroviruses (EVs) are the leading cause of aseptic meningitis, which is the most frequent central nervous system infection worldwide. We aimed to characterize the EVs involved in an aseptic meningitis outbreak in Korea in 2008. In Korea, Echovirus type 30 (E30) and E6 have been associated with outbreaks and frequent meningitis. During 2008, through nationwide surveillance, we collected specimens from 758 patients with aseptic meningitis-related clinical manifestations. The detection of EVs from specimens was subjected to a diagnostic real-time RT-PCR in the 5' NCR. A semi-nested polymerase chain reaction (PCR) to amplify sequences from the VP1 region and sequence comparison with reference strains registered in Genbank was performed for the genotype determination. Most patients (98%) in this outbreak were children < 15 years of age. The temporal distribution of the E6 and E30 epidemics showed an obvious seasonal pattern during the short period from June to July. A large majority of the EV-positive patients experienced fever, headache, vomiting, and neck stiffness. Some patients also showed cold symptoms, sore throat, altered mental status, and seizures. We did not observe a higher fatality rate in children with E6 or E30 infection. Most of the patients recovered uneventfully. In most cases, the cerebrospinal fluid (CSF) profile was studied, and generally showed a higher than normal white blood cell count (≥ 5/mm3). We detected EVs from 513 patients (67.68%) and identified the EV genotype in 287 patients. E30 (n = 155, 50.4%) and E6 (n = 95, 33.1%) were the predominant genotypes. E9, E1, E7, E16, Coxsackievirus A3, 4, 6, Coxsackievirus B1, 3, and 10 were also identified. According to phylogenetic analysis, E30 belonged to subgroup 4b, and E6, to the C4 subgroup. Conclusively, aseptic meningitis was the most common manifestation in children with either echovirus 30 or 6 infection. Identification of E6 and E30 as the prominent EVs in the 2008 outbreak in South Korea shows the potential of EVs to cause a serious disease in an unpredictable (fashion. Our findings provide new) insights into the clinical and virological features of the aseptic meningitis outbreak caused by E30 and E6.
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Epidemics of viral meningitis caused by echovirus 6 and 30 in Korea in 2008
Virology Journal, 2012Co-Authors: Hye-jin Kim, Seoyeon Hwang, Byounghak Kang, Jiyoung Hong, Kisang Kim, Doo-sung CheonAbstract:Background Enteroviruses (EVs) are the leading cause of aseptic meningitis, which is the most frequent central nervous system infection worldwide. We aimed to characterize the EVs involved in an aseptic meningitis outbreak in Korea in 2008. In Korea, Echovirus type 30 (E30) and E6 have been associated with outbreaks and frequent meningitis. Methods During 2008, through nationwide surveillance, we collected specimens from 758 patients with aseptic meningitis-related clinical manifestations. The detection of EVs from specimens was subjected to a diagnostic real-time RT-PCR in the 5' NCR. A semi-nested polymerase chain reaction (PCR) to amplify sequences from the VP1 region and sequence comparison with reference strains registered in Genbank was performed for the genotype determination. Results Most patients (98%) in this outbreak were children < 15 years of age. The temporal distribution of the E6 and E30 epidemics showed an obvious seasonal pattern during the short period from June to July. A large majority of the EV-positive patients experienced fever, headache, vomiting, and neck stiffness. Some patients also showed cold symptoms, sore throat, altered mental status, and seizures. We did not observe a higher fatality rate in children with E6 or E30 infection. Most of the patients recovered uneventfully. In most cases, the cerebrospinal fluid (CSF) profile was studied, and generally showed a higher than normal white blood cell count (≥ 5/mm^3). We detected EVs from 513 patients (67.68%) and identified the EV genotype in 287 patients. E30 (n = 155, 50.4%) and E6 (n = 95, 33.1%) were the predominant genotypes. E9, E1, E7, E16, Coxsackievirus A3, 4, 6, Coxsackievirus B1, 3, and 10 were also identified. According to phylogenetic analysis, E30 belonged to subgroup 4b, and E6, to the C4 subgroup. Conclusions Conclusively, aseptic meningitis was the most common manifestation in children with either echovirus 30 or 6 infection. Identification of E6 and E30 as the prominent EVs in the 2008 outbreak in South Korea shows the potential of EVs to cause a serious disease in an unpredictable (fashion. Our findings provide new) insights into the clinical and virological features of the aseptic meningitis outbreak caused by E30 and E6.
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Epidemics of enterovirus infection in Chungnam Korea, 2008 and 2009
Virology Journal, 2011Co-Authors: Kyoungah Baek, Kwisung Park, Jeesuk Yu, Insoo Rheem, Seoyeon Hwang, Doo-sung Cheon, Jaehyoung Song, Youngjin Choi, Joonsoo ParkAbstract:Previously, we explored the epidemic pattern and molecular characterization of enteroviruses isolated in Chungnam, Korea from 2005 to 2006. The present study extended these observations to 2008 and 2009. In this study, enteroviruses showed similar seasonal prevalent pattern from summer to fall and age distribution to previous investigation. The most prevalent month was July: 42.9% in 2008 and 31.9% in 2009. The highest rate of enterovirus-positive samples occurred in children < 1-year-old-age. Enterovirus-positive samples were subjected to sequence determination of the VP1 region, which resolved the isolated enteroviruses into 10 types in 2008 (Coxsackievirus A4, A16, B1, B3, echovirus 6, 7, 9, 11, 16, and 30) and 8 types in 2009 (Coxsackievirus A2, A4, A5, A16, B1, B5, echovirus 11, and enterovirus 71). The most prevalent enterovirus serotype in 2008 and 2009 was echovirus 30 and Coxsackievirus B1, respectively, whereas echovirus 18 and echovirus 5 were the most prevalent types in 2005 and 2006, respectively. Comparison of Coxsackievirus B1 and B5 of prevalent enterovirus type in Korea in 2009 with reference strains of each same serotype were conducted to genetic analysis by a phylogenetic tree. The sequences of Coxsackievirus B1 strains segregated into four distinct clusters (A, B, C, and D) with some temporal and regional sub-clustering. Most of Korean Coxsackievirus B1 strains in 2008 and 2009 were in cluster D, while only "Kor08-CVB1-001CN" was cluster C. The Coxsackievirus B5 strains segregated in five distinct genetic groups (clusters A-E) were supported by high bootstrap values. The Korean strains isolated in 2001 belonged to cluster D, whereas Korean strains isolated in 2005 and 2009 belonged to cluster E. Comparison of the VP1 amino acid sequences of the Korean Coxsackievirus B5 isolates with reference strains revealed amino acid sequence substitutions at nine amino acid sequences (532, 562, 570, 571, 576-578, 582, 583, and 585).
