Understanding Amino Acid Mutations in Hepatitis B Virus Proteins for Rational Design of Vaccines and Drugs.

The hepatitis B virus (HBV) genome encodes four proteins, i.e., DNA polymerase, surface protein, X, and core proteins. HBV undergoes different selective pressures for drug resistance and immune/vaccine escape and mutations are common for the HBV proteins. We here collected all the reported amino acid mutations happened in these four HBV proteins and studied their patterns. The relationship between the mutations and epitopic functions are investigated with bioinformatics tools, based on their sequence information. Some interesting results are observed for the mutation patterns, such as we found the serine and threonine are both for frequently mutated residues and mutant residues, while the tryptophan and methionine have low mutability. The results provide important information for the understanding of the molecular mechanism of virus evolution and therefore will facilitate the future rational design of HBV vaccines or drugs.

[1]  Manoj Bhasin,et al.  Prediction of promiscuous and high-affinity mutated MHC binders. , 2003, Hybridoma and hybridomics.

[2]  Harinder Singh,et al.  Improved Method for Linear B-Cell Epitope Prediction Using Antigen’s Primary Sequence , 2013, PloS one.

[3]  G. Gong,et al.  Hepatitis B virus mutation may play a role in hepatocellular carcinoma recurrence: A systematic review and meta‐regression analysis , 2015, Journal of gastroenterology and hepatology.

[4]  Bo Yao,et al.  Conformational B-Cell Epitope Prediction on Antigen Protein Structures: A Review of Current Algorithms and Comparison with Common Binding Site Prediction Methods , 2013, PloS one.

[5]  Boping Zhou,et al.  Exome sequencing of hepatitis B virus–associated hepatocellular carcinoma , 2012, Nature Genetics.

[6]  Colin W Shepard,et al.  Hepatitis B virus infection: epidemiology and vaccination. , 2006, Epidemiologic reviews.

[7]  H. Rammensee,et al.  SYFPEITHI: database for MHC ligands and peptide motifs , 1999, Immunogenetics.

[8]  Meng Ge,et al.  EPMLR: sequence-based linear B-cell epitope prediction method using multiple linear regression , 2014, BMC Bioinformatics.

[9]  Hanah Margalit,et al.  A structure-based approach for prediction of MHC-binding peptides. , 2004, Methods.

[10]  J. Hammer,et al.  New methods to predict MHC-binding sequences within protein antigens. , 1995, Current opinion in immunology.

[11]  C. Chu,et al.  Hepatitis B virus infection , 2009, The Lancet.

[12]  Aiping Wu,et al.  Mapping of H3N2 influenza antigenic evolution in China reveals a strategy for vaccine strain recommendation , 2012, Nature Communications.

[13]  Y. N. Park,et al.  Large liver cell change in hepatitis B virus–related liver cirrhosis , 2009, Hepatology.

[14]  Vasant Honavar,et al.  Recent advances in B-cell epitope prediction methods , 2010, Immunome research.

[15]  Deborah Hix,et al.  The immune epitope database (IEDB) 3.0 , 2014, Nucleic Acids Res..

[16]  Z. Cao,et al.  MHC-BPS: MHC-binder prediction server for identifying peptides of flexible lengths from sequence-derived physicochemical properties , 2006, Immunogenetics.

[17]  R. Abagyan,et al.  Ab initio prediction of peptide‐MHC binding geometry for diverse class I MHC allotypes , 2006, Proteins.

[18]  Ji Wan,et al.  SVRMHC prediction server for MHC-binding peptides , 2006, BMC Bioinformatics.

[19]  Jiajia Chen,et al.  A systems biology perspective on rational design of peptide vaccine against virus infections. , 2012, Current topics in medicinal chemistry.

[20]  Jinyan Li,et al.  B-cell epitope prediction through a graph model , 2012, BMC Bioinformatics.

[21]  Darren R Flower,et al.  Class I T-cell epitope prediction: improvements using a combination of proteasome cleavage, TAP affinity, and MHC binding. , 2006, Molecular immunology.

[22]  Sofia Khan,et al.  Spectrum of disease-causing mutations in protein secondary structures , 2007, BMC Structural Biology.

[23]  Hau-San Wong,et al.  MHC binding prediction with KernelRLSpan and its variations. , 2014, Journal of immunological methods.

[24]  Chaomei Chen,et al.  Web site design with the patron in mind: A step-by-step guide for libraries , 2006 .

[25]  Morten Nielsen,et al.  Reliable B Cell Epitope Predictions: Impacts of Method Development and Improved Benchmarking , 2012, PLoS Comput. Biol..

[26]  Jiajia Shen.  Computational Analysis of Amino Acid Mutation: A Proteome Wide Perspective , 2009 .

[27]  Alan Kay,et al.  HBVdb: a knowledge database for Hepatitis B Virus , 2012, Nucleic Acids Res..

[28]  Guan-Tarn Huang,et al.  Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. , 2006, JAMA.

[29]  Qing Zhang,et al.  Immune epitope database analysis resource (IEDB-AR) , 2008, Nucleic Acids Res..

[30]  Bairong Shen,et al.  Conservation and covariance in PH domain sequences: physicochemical profile and information theoretical analysis of XLA-causing mutations in the Btk PH domain. , 2004, Protein engineering, design & selection : PEDS.

[31]  M. Mizokami,et al.  Molecular Evolution of Hepatitis B Virus over 25 Years , 2006, Journal of Virology.

[32]  Oliver Kohlbacher,et al.  SVMHC: a server for prediction of MHC-binding peptides , 2006, Nucleic Acids Res..

[33]  P. Reche,et al.  Customized Predictions of Peptide–MHC Binding and T-Cell Epitopes Using EPIMHC , 2014, Methods in molecular biology.

[34]  Avner Schlessinger,et al.  Towards a consensus on datasets and evaluation metrics for developing B‐cell epitope prediction tools , 2007, Journal of molecular recognition : JMR.

[35]  Paul J. Kennedy,et al.  Enhancing In Silico Protein-Based Vaccine Discovery for Eukaryotic Pathogens Using Predicted Peptide-MHC Binding and Peptide Conservation Scores , 2014, PloS one.

[36]  Tommy F. Liu,et al.  Hepatitis B virus reverse transcriptase sequence variant database for sequence analysis and mutation discovery. , 2010, Antiviral research.

[37]  Y. Liaw,et al.  Hepatitis B virus DNA level predicts hepatic decompensation in patients with acute exacerbation of chronic hepatitis B. , 2010, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[38]  Mathias M Schuler,et al.  SYFPEITHI: database for searching and T-cell epitope prediction. , 2007, Methods in molecular biology.

[39]  Morten Nielsen,et al.  Improved method for predicting linear B-cell epitopes , 2006, Immunome research.

[40]  C. Walker,et al.  Efficacy of hepatitis B vaccine against antiviral drug‐resistant hepatitis B virus mutants in the chimpanzee model , 2009, Hepatology.

[41]  Pingping Guan,et al.  MHCPred: a server for quantitative prediction of peptide-MHC binding , 2003, Nucleic Acids Res..

[42]  Pierre Baldi,et al.  PEPITO: improved discontinuous B-cell epitope prediction using multiple distance thresholds and half sphere exposure , 2008, Bioinform..