Using Structural Bioinformatics To Study The Role Of HBV Mutations In Immune Escape Of Liver Cancer

HBV(Hepatitis B virus)infection is an important issue that threatens the health of people in China and globally,when under the pressure of selection of host liver cells and immune cells,HBV virus may undergo spontaneous mutations,which alters the binding force of the antigen peptides produced by the virus to MHC(major histocompatibility complex)class I molecules.This would reduce the presentation of antigen peptides by MHC I molecules,resulting in immunity escape.Different ethnic groups may be susceptible genotype of HBV strains,so under the background of this topic in the data,choose the HLA-A * 11: 01 subtype that appears frequently in Chinese population and the HLA-A * 02: 01 subtype that appears frequently in European and American populations.At the same time,the HBV subtypes susceptible to Asian populations and European and American populations and the C and S coding region sequences encoding major antigens were collected.In the subtype A susceptible to European and American populations,1086 virus sequences were collected in the C coding region,1390 virus sequences were collected in the S coding region.In subtypes B and C susceptible to human infection in Asia,1573 and 2115 sequences were collected in the C coding region,and 2581 and 2639 virus sequences were collected in the S coding region,respectively.By comparing HBV virus sequences,conservativeness,physicochemical properties,predicted antigen peptide scoring and other bioinformatics analysis,21 candidate key mutations were selected.Then based on key mutations,the complex structure of the predicted antigen peptide and MHC class I molecule produced by molecular docking was constructed,and then the peptide-MHC complex was screened using amino acid scanning analysis to select 11 affinity for the antigen peptide and MHC molecule The mutations causing the effects are: I155 V,V149A,L149 V,I156L,L213 F,I256M,V351 A,V354A,M372 V,M372I,L389 V.The molecular dynamics method was used to calculate and compare the changes in the overall binding free energy before and after the mutation.The calculation results show that these 11 mutations will cause the binding free energy to decrease to varying degrees,among them,the mutation of L149 V has the greatest influence on the binding free energy,which will be reduced from the original136.52 kcal / mol to 68.10 kcal / mol,with a decrease of up to 50%,it indicates that the mutation of this site weakens the binding force between the corresponding antigen peptide and MHC.This study found that in the HLA-A * 11: 01 and HLA-A * 02: 01 subtypes that occur frequently in Chinese and European and American populations,the key mutations of HBV virus in the C and S coding regions will affect the The affinity between the mutant antigen peptide and the corresponding MHC,so it is speculated that the candidate key mutation gene will lead to immune escape of the body,which may be related to the occurrence of liver cancer related to HBV infection.