Abstract
BackgroundHCV 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 ~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.MethodsThe present study analyzed structural and functional features of 345 sequences of HCV-NS5A genotypes 1 or 3, using in silico tools.ResultsThere 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.ConclusionThis 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.
Highlights
Hepatitis C is a major health problem; it is highly prevalent worldwide and has a high probability of persistence [1,2]
Considering the genotypes, the average percentages of alanine, glutamic acid, glutamine and tyrosine present in the Non-structural 5A (NS5A) protein were different between the genotypes 1a, 1b and 3
This research presents new insights regarding Hepatitis C virus (HCV) NS5A genotypes 1 and 3. It demonstrates the importance of applying bioinformatic tools to the study of proteins that are difficult to investigate by other experimental procedures
Summary
Hepatitis C is a major health problem; it is highly prevalent worldwide and has a high probability of persistence [1,2]. In. The HCV RNA genome translates a polyprotein that is cleaved by viral and host proteases to generate ten structural and non-structural proteins [10,11,12]. Among the non-structural proteins, NS5A is a phosphoprotein critical for the HCV life cycle. It is composed of approximately 447 amino acids and may participate in viral RNA replication, modulation of cell signaling pathways, interferon response, pathogenesis and apoptosis regulation. It is a major cause of chronic liver disease. 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
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