New insights regarding HCV-NS5A structure/function and indication of genotypic differences
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/1743-422X-9-14 http://hdl.handle.net/11449/21652 |
Resumo: | Background: HCV is prevalent throughout the world. It is a major cause of chronic liver disease. There is no effective vaccine and the most common therapy, based on Peginterferon, has a success rate of similar to 50%. The mechanisms underlying viral resistance have not been elucidated but it has been suggested that both host and virus contribute to therapy outcome. Non-structural 5A (NS5A) protein, a critical virus component, is involved in cellular and viral processes.Methods: The present study analyzed structural and functional features of 345 sequences of HCV-NS5A genotypes 1 or 3, using in silico tools.Results: There was residue type composition and secondary structure differences between the genotypes. In addition, second structural variance were statistical different for each response group in genotype 3. A motif search indicated conserved glycosylation, phosphorylation and myristoylation sites that could be important in structural stabilization and function. Furthermore, a highly conserved integrin ligation site was identified, and could be linked to nuclear forms of NS5A. ProtFun indicated NS5A to have diverse enzymatic and nonenzymatic activities, participating in a great range of cell functions, with statistical difference between genotypes.Conclusion: This study presents new insights into the HCV-NS5A. It is the first study that using bioinformatics tools, suggests differences between genotypes and response to therapy that can be related to NS5A protein features. Therefore, it emphasizes the importance of using bioinformatics tools in viral studies. Data acquired herein will aid in clarifying the structure/function of this protein and in the development of antiviral agents. |
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New insights regarding HCV-NS5A structure/function and indication of genotypic differencesHepatitis C virusNon-structural 5A proteinBioinformaticsGenotypeQuasispeciesIFN responseBackground: HCV is prevalent throughout the world. It is a major cause of chronic liver disease. There is no effective vaccine and the most common therapy, based on Peginterferon, has a success rate of similar to 50%. The mechanisms underlying viral resistance have not been elucidated but it has been suggested that both host and virus contribute to therapy outcome. Non-structural 5A (NS5A) protein, a critical virus component, is involved in cellular and viral processes.Methods: The present study analyzed structural and functional features of 345 sequences of HCV-NS5A genotypes 1 or 3, using in silico tools.Results: There was residue type composition and secondary structure differences between the genotypes. In addition, second structural variance were statistical different for each response group in genotype 3. A motif search indicated conserved glycosylation, phosphorylation and myristoylation sites that could be important in structural stabilization and function. Furthermore, a highly conserved integrin ligation site was identified, and could be linked to nuclear forms of NS5A. ProtFun indicated NS5A to have diverse enzymatic and nonenzymatic activities, participating in a great range of cell functions, with statistical difference between genotypes.Conclusion: This study presents new insights into the HCV-NS5A. It is the first study that using bioinformatics tools, suggests differences between genotypes and response to therapy that can be related to NS5A protein features. Therefore, it emphasizes the importance of using bioinformatics tools in viral studies. Data acquired herein will aid in clarifying the structure/function of this protein and in the development of antiviral agents.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)São Paulo State Univ UNESP, Dept Biol, Sao Jose do Rio Preto, SP, BrazilSão Paulo Univ USP, Dept Clin Med, São Paulo, BrazilInstituto Butantan, Viral Immunol Lab, São Paulo, BrazilLab Estudos Genom, BR-15054000 Sao Jose do Rio Preto, SP, BrazilSão Paulo State Univ UNESP, Dept Biol, Sao Jose do Rio Preto, SP, BrazilBiomed Central Ltd.Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Instituto ButantanLab Estudos GenomYamasaki, Lilian H. T. [UNESP]Arcuri, Helen A.Jardim, Ana Carolina G. [UNESP]Bittar, Cintia [UNESP]de Carvalho-Mello, Isabel Maria V. G.Rahal, Paula [UNESP]2014-05-20T14:01:17Z2014-05-20T14:01:17Z2012-01-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article10application/pdfhttp://dx.doi.org/10.1186/1743-422X-9-14Virology Journal. London: Biomed Central Ltd., v. 9, p. 10, 2012.1743-422Xhttp://hdl.handle.net/11449/2165210.1186/1743-422X-9-14WOS:000304652900001WOS000304652900001.pdf79910823626712120000-0001-5693-6148Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengVirology Journal2.465info:eu-repo/semantics/openAccess2023-11-23T06:11:22Zoai:repositorio.unesp.br:11449/21652Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T18:29:31.045761Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
New insights regarding HCV-NS5A structure/function and indication of genotypic differences |
title |
New insights regarding HCV-NS5A structure/function and indication of genotypic differences |
spellingShingle |
New insights regarding HCV-NS5A structure/function and indication of genotypic differences Yamasaki, Lilian H. T. [UNESP] Hepatitis C virus Non-structural 5A protein Bioinformatics Genotype Quasispecies IFN response |
title_short |
New insights regarding HCV-NS5A structure/function and indication of genotypic differences |
title_full |
New insights regarding HCV-NS5A structure/function and indication of genotypic differences |
title_fullStr |
New insights regarding HCV-NS5A structure/function and indication of genotypic differences |
title_full_unstemmed |
New insights regarding HCV-NS5A structure/function and indication of genotypic differences |
title_sort |
New insights regarding HCV-NS5A structure/function and indication of genotypic differences |
author |
Yamasaki, Lilian H. T. [UNESP] |
author_facet |
Yamasaki, Lilian H. T. [UNESP] Arcuri, Helen A. Jardim, Ana Carolina G. [UNESP] Bittar, Cintia [UNESP] de Carvalho-Mello, Isabel Maria V. G. Rahal, Paula [UNESP] |
author_role |
author |
author2 |
Arcuri, Helen A. Jardim, Ana Carolina G. [UNESP] Bittar, Cintia [UNESP] de Carvalho-Mello, Isabel Maria V. G. Rahal, Paula [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) Instituto Butantan Lab Estudos Genom |
dc.contributor.author.fl_str_mv |
Yamasaki, Lilian H. T. [UNESP] Arcuri, Helen A. Jardim, Ana Carolina G. [UNESP] Bittar, Cintia [UNESP] de Carvalho-Mello, Isabel Maria V. G. Rahal, Paula [UNESP] |
dc.subject.por.fl_str_mv |
Hepatitis C virus Non-structural 5A protein Bioinformatics Genotype Quasispecies IFN response |
topic |
Hepatitis C virus Non-structural 5A protein Bioinformatics Genotype Quasispecies IFN response |
description |
Background: HCV is prevalent throughout the world. It is a major cause of chronic liver disease. There is no effective vaccine and the most common therapy, based on Peginterferon, has a success rate of similar to 50%. The mechanisms underlying viral resistance have not been elucidated but it has been suggested that both host and virus contribute to therapy outcome. Non-structural 5A (NS5A) protein, a critical virus component, is involved in cellular and viral processes.Methods: The present study analyzed structural and functional features of 345 sequences of HCV-NS5A genotypes 1 or 3, using in silico tools.Results: There was residue type composition and secondary structure differences between the genotypes. In addition, second structural variance were statistical different for each response group in genotype 3. A motif search indicated conserved glycosylation, phosphorylation and myristoylation sites that could be important in structural stabilization and function. Furthermore, a highly conserved integrin ligation site was identified, and could be linked to nuclear forms of NS5A. ProtFun indicated NS5A to have diverse enzymatic and nonenzymatic activities, participating in a great range of cell functions, with statistical difference between genotypes.Conclusion: This study presents new insights into the HCV-NS5A. It is the first study that using bioinformatics tools, suggests differences between genotypes and response to therapy that can be related to NS5A protein features. Therefore, it emphasizes the importance of using bioinformatics tools in viral studies. Data acquired herein will aid in clarifying the structure/function of this protein and in the development of antiviral agents. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-01-12 2014-05-20T14:01:17Z 2014-05-20T14:01:17Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1186/1743-422X-9-14 Virology Journal. London: Biomed Central Ltd., v. 9, p. 10, 2012. 1743-422X http://hdl.handle.net/11449/21652 10.1186/1743-422X-9-14 WOS:000304652900001 WOS000304652900001.pdf 7991082362671212 0000-0001-5693-6148 |
url |
http://dx.doi.org/10.1186/1743-422X-9-14 http://hdl.handle.net/11449/21652 |
identifier_str_mv |
Virology Journal. London: Biomed Central Ltd., v. 9, p. 10, 2012. 1743-422X 10.1186/1743-422X-9-14 WOS:000304652900001 WOS000304652900001.pdf 7991082362671212 0000-0001-5693-6148 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Virology Journal 2.465 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
10 application/pdf |
dc.publisher.none.fl_str_mv |
Biomed Central Ltd. |
publisher.none.fl_str_mv |
Biomed Central Ltd. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128938340253696 |