Weak linkage in hepatitis C PePHD: identification of mutation prone point that can lead to failure of antiviral therapy for prevention of hepatocellular carcinoma.
Hepatitis C is an important blood borne infection caused by hepatitis C virus (HCV). Chronic inflammation induced by this viral infection and its role in carcinogenesis are well recognized. The treatment of HCV infection has developed enormously over recent years and is believed to be a good way for stopping of carcinogenesis process. However, mutation of the virus is an important factor that can bring drug resistance. Presently, prediction of protein nanostructure and function is a great challenge in the proteomics and structural genomics era. To identify points which are vulnerable to mutation is a new trend to expand the knowledge at the genomic and proteomic levels Here, the author performed a bioinformatic analysis to determine positions that trend to comply with peptide motifs in the amino acid sequence of HCV protein kinase -eIF2-alpha phosphorylation homology domain (PePHD). To identify weak linkage in HCV PePHD, a new bioinformatic tool, GlobPlot, was used. Positions 2-7, 29-39, 53-57, 90-98, 123-133, 202-227, 324-355, 439-448 were identified as positions resistant to mutation. Some are already known and others are newly discovered. Based on this study, weak linkages in HCV PePHD could be identified and can be good information for expectation of possible new mutations that can lead to failure of HCV therapy. In addition, the results from this study can be good information for further research on the diagnosis for mutants HCV and vaccine development.
Wiwanitkit
Viroj
V
Department of Laboratory Medicine, Chulalongkorn University, Bangkok, Thailand. wviroj@yahoo.com
D000998:Antiviral Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control*; D019295:Computational Biology; D024882:Drug Resistance, Viral / Q000235:genetics*; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control; D009154:Mutation / Q000235:genetics*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D019892:eIF-2 Kinase / Q000737:chemistry / Q000235:genetics*
D000998:Antiviral Agents; D019892:eIF-2 Kinase