New insights regarding HCV-NS5A structure/function and indication of genotypic differences

Autor: Cíntia Bittar, Ana Carolina Gomes Jardim, Lílian Hiromi Tomonari Yamasaki, Paula Rahal, Isabel Maria Vicente Guedes de Carvalho-Mello, Helen Andrade Arcuri
Přispěvatelé: Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP), Instituto Butantan, Lab Estudos Genom
Rok vydání: 2012
Předmět:
Zdroj: Virology Journal
Web of Science
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
Virology Journal, Vol 9, Iss 1, p 14 (2012)
ISSN: 1743-422X
0003-0465
DOI: 10.1186/1743-422x-9-14
Popis: Made available in DSpace on 2013-08-28T14:13:39Z (GMT). No. of bitstreams: 1 WOS000304652900001.pdf: 446535 bytes, checksum: af9d46e5ffbd620fed174b57ea513272 (MD5) Made available in DSpace on 2013-09-30T18:42:10Z (GMT). No. of bitstreams: 2 WOS000304652900001.pdf: 446535 bytes, checksum: af9d46e5ffbd620fed174b57ea513272 (MD5) WOS000304652900001.pdf.txt: 42811 bytes, checksum: 9d647c42223a35ef1f0dee27ddea4919 (MD5) Previous issue date: 2012-01-12 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:01:17Z No. of bitstreams: 2 WOS000304652900001.pdf: 446535 bytes, checksum: af9d46e5ffbd620fed174b57ea513272 (MD5) WOS000304652900001.pdf.txt: 42811 bytes, checksum: 9d647c42223a35ef1f0dee27ddea4919 (MD5) Made available in DSpace on 2014-05-20T14:01:17Z (GMT). No. of bitstreams: 2 WOS000304652900001.pdf: 446535 bytes, checksum: af9d46e5ffbd620fed174b57ea513272 (MD5) WOS000304652900001.pdf.txt: 42811 bytes, checksum: 9d647c42223a35ef1f0dee27ddea4919 (MD5) Previous issue date: 2012-01-12 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) 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. São Paulo State Univ UNESP, Dept Biol, Sao Jose do Rio Preto, SP, Brazil São Paulo Univ USP, Dept Clin Med, São Paulo, Brazil Instituto Butantan, Viral Immunol Lab, São Paulo, Brazil Lab Estudos Genom, BR-15054000 Sao Jose do Rio Preto, SP, Brazil São Paulo State Univ UNESP, Dept Biol, Sao Jose do Rio Preto, SP, Brazil
Databáze: OpenAIRE
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