Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes

Autores
Ostermann Porcel, María Victoria; Vizoso Pinto, María Guadalupe; Haase, Rudolf; Nitschko, Hans; Jaeger, Simone; Sander, Michaela; Motz, Manfred; Mohn, Ulrich; Baiker, Armin
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV) is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF) 2 and ORF3. The largest ORF1 (poly-)protein, however, is not part of current testing formats. Methods. From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3) by performing receiver operator characteristics, logistic regression and correlation analysis. Results: HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens. Conclusions: The diagnostic value of identified ORF1 epitopes might not necessarily improve sensitivity and specificity, but broaden the overall quality of existing test systems. ORF2 and ORF3-antigens are still commonly used in diagnostic assays and possibly hold the potential to serologically differentiate between genotype 1 and 3 infections. Our systematic approach is a suitable method to investigate HEV domains for their serologic antigenicity. Epitope screening of native viral domains could be a preferable tool in developing new serologic test components.
Fil: Ostermann Porcel, María Victoria. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Fil: Vizoso Pinto, María Guadalupe. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Haase, Rudolf. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania
Fil: Nitschko, Hans. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania
Fil: Jaeger, Simone. Mikrogen GmbH; Alemania
Fil: Sander, Michaela. Mikrogen Gmbh; Alemania
Fil: Motz, Manfred. Mikrogen Gmbh; Alemania
Fil: Mohn, Ulrich. Mikrogen Gmbh; Alemania
Fil: Baiker, Armin. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania. Bavarian Health and Food Safety Authority; Alemania
Materia
HEPATITIS E VIRUS
GENOMW-WIDE
SEROLOGY
VIRAL ANTIGENS
DIAGNOSTIC TEST DEVELOPMENT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/69950
Acceder
id CONICETDig_de82cdf44ecbbdd6be21cce86c7f9e59
oai_identifier_str oai:ri.conicet.gov.ar:11336/69950
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Systematic screening for novel, serologically reactive Hepatitis e Virus epitopesOstermann Porcel, María VictoriaVizoso Pinto, María GuadalupeHaase, RudolfNitschko, HansJaeger, SimoneSander, MichaelaMotz, ManfredMohn, UlrichBaiker, ArminHEPATITIS E VIRUSGENOMW-WIDESEROLOGYVIRAL ANTIGENSDIAGNOSTIC TEST DEVELOPMENThttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV) is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF) 2 and ORF3. The largest ORF1 (poly-)protein, however, is not part of current testing formats. Methods. From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3) by performing receiver operator characteristics, logistic regression and correlation analysis. Results: HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens. Conclusions: The diagnostic value of identified ORF1 epitopes might not necessarily improve sensitivity and specificity, but broaden the overall quality of existing test systems. ORF2 and ORF3-antigens are still commonly used in diagnostic assays and possibly hold the potential to serologically differentiate between genotype 1 and 3 infections. Our systematic approach is a suitable method to investigate HEV domains for their serologic antigenicity. Epitope screening of native viral domains could be a preferable tool in developing new serologic test components.Fil: Ostermann Porcel, María Victoria. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Vizoso Pinto, María Guadalupe. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Haase, Rudolf. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; AlemaniaFil: Nitschko, Hans. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; AlemaniaFil: Jaeger, Simone. Mikrogen GmbH; AlemaniaFil: Sander, Michaela. Mikrogen Gmbh; AlemaniaFil: Motz, Manfred. Mikrogen Gmbh; AlemaniaFil: Mohn, Ulrich. Mikrogen Gmbh; AlemaniaFil: Baiker, Armin. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania. Bavarian Health and Food Safety Authority; AlemaniaBioMed Central2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/69950Ostermann Porcel, María Victoria; Vizoso Pinto, María Guadalupe; Haase, Rudolf; Nitschko, Hans; Jaeger, Simone; et al.; Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes; BioMed Central; Virology Journal; 9; 1-2012; 1-91743-422XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.virologyj.com/content/9/1/28/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1186/1743-422X-9-28info:eu-repo/semantics/altIdentifier/url/https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-9-28info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:50:20Zoai:ri.conicet.gov.ar:11336/69950instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:50:20.332CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes
title Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes
spellingShingle Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes
Ostermann Porcel, María Victoria
HEPATITIS E VIRUS
GENOMW-WIDE
SEROLOGY
VIRAL ANTIGENS
DIAGNOSTIC TEST DEVELOPMENT
title_short Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes
title_full Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes
title_fullStr Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes
title_full_unstemmed Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes
title_sort Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes
dc.creator.none.fl_str_mv Ostermann Porcel, María Victoria
Vizoso Pinto, María Guadalupe
Haase, Rudolf
Nitschko, Hans
Jaeger, Simone
Sander, Michaela
Motz, Manfred
Mohn, Ulrich
Baiker, Armin
author Ostermann Porcel, María Victoria
author_facet Ostermann Porcel, María Victoria
Vizoso Pinto, María Guadalupe
Haase, Rudolf
Nitschko, Hans
Jaeger, Simone
Sander, Michaela
Motz, Manfred
Mohn, Ulrich
Baiker, Armin
author_role author
author2 Vizoso Pinto, María Guadalupe
Haase, Rudolf
Nitschko, Hans
Jaeger, Simone
Sander, Michaela
Motz, Manfred
Mohn, Ulrich
Baiker, Armin
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HEPATITIS E VIRUS
GENOMW-WIDE
SEROLOGY
VIRAL ANTIGENS
DIAGNOSTIC TEST DEVELOPMENT
topic HEPATITIS E VIRUS
GENOMW-WIDE
SEROLOGY
VIRAL ANTIGENS
DIAGNOSTIC TEST DEVELOPMENT
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV) is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF) 2 and ORF3. The largest ORF1 (poly-)protein, however, is not part of current testing formats. Methods. From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3) by performing receiver operator characteristics, logistic regression and correlation analysis. Results: HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens. Conclusions: The diagnostic value of identified ORF1 epitopes might not necessarily improve sensitivity and specificity, but broaden the overall quality of existing test systems. ORF2 and ORF3-antigens are still commonly used in diagnostic assays and possibly hold the potential to serologically differentiate between genotype 1 and 3 infections. Our systematic approach is a suitable method to investigate HEV domains for their serologic antigenicity. Epitope screening of native viral domains could be a preferable tool in developing new serologic test components.
Fil: Ostermann Porcel, María Victoria. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Fil: Vizoso Pinto, María Guadalupe. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Haase, Rudolf. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania
Fil: Nitschko, Hans. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania
Fil: Jaeger, Simone. Mikrogen GmbH; Alemania
Fil: Sander, Michaela. Mikrogen Gmbh; Alemania
Fil: Motz, Manfred. Mikrogen Gmbh; Alemania
Fil: Mohn, Ulrich. Mikrogen Gmbh; Alemania
Fil: Baiker, Armin. Ludwig Maximilians Universitat. Max Von Pettenkofer Institute. Cátedra Virology; Alemania. Bavarian Health and Food Safety Authority; Alemania
description Background: The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV) is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF) 2 and ORF3. The largest ORF1 (poly-)protein, however, is not part of current testing formats. Methods. From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3) by performing receiver operator characteristics, logistic regression and correlation analysis. Results: HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens. Conclusions: The diagnostic value of identified ORF1 epitopes might not necessarily improve sensitivity and specificity, but broaden the overall quality of existing test systems. ORF2 and ORF3-antigens are still commonly used in diagnostic assays and possibly hold the potential to serologically differentiate between genotype 1 and 3 infections. Our systematic approach is a suitable method to investigate HEV domains for their serologic antigenicity. Epitope screening of native viral domains could be a preferable tool in developing new serologic test components.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/69950
Ostermann Porcel, María Victoria; Vizoso Pinto, María Guadalupe; Haase, Rudolf; Nitschko, Hans; Jaeger, Simone; et al.; Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes; BioMed Central; Virology Journal; 9; 1-2012; 1-9
1743-422X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/69950
identifier_str_mv Ostermann Porcel, María Victoria; Vizoso Pinto, María Guadalupe; Haase, Rudolf; Nitschko, Hans; Jaeger, Simone; et al.; Systematic screening for novel, serologically reactive Hepatitis e Virus epitopes; BioMed Central; Virology Journal; 9; 1-2012; 1-9
1743-422X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.virologyj.com/content/9/1/28/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1186/1743-422X-9-28
info:eu-repo/semantics/altIdentifier/url/https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-9-28
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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