Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality.Hepatitis B virus(HBV)infection can be controlled by vaccines,antiviral treatment,and ...Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality.Hepatitis B virus(HBV)infection can be controlled by vaccines,antiviral treatment,and by interrupting transmission.Rare vaccine escape mutants are serious because they eliminate vaccine protection.Here,we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation.The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation.The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R,P120 Q,and Q129 P.The patient was successfully treated with entecavir.The epidemiological reasons for this subgenotype,which is extremely rare in Western Europe,were unclear.This case illustrates that second-generation vaccines are not always effective in a specific group of patients.展开更多
AIM To investigate the role of subgenotype specific RNA secondary structure in the compartment specific selection of hepatitis B virus(HBV)immune escape mutations.METHODS This study was based on the analysis of the sp...AIM To investigate the role of subgenotype specific RNA secondary structure in the compartment specific selection of hepatitis B virus(HBV)immune escape mutations.METHODS This study was based on the analysis of the specific observation of HBV subgenotype A1 in the serum/plasma,while subgenotype A2 with G145R mutation in the peripheral blood leukocytes(PBLs).Genetic variability found among the two subgenotypes was used for prediction and comparison of the full length pregenomic RNA(pgRNA)secondary structure and base pairings.RNA secondary structures were predicted for 37℃using the Vienna RNA fold server,using default parameters.Visualization and detailed analysis was done using RNA shapes program.RESULTS In this analysis,using similar algorithm and conditions,entirely different pgRNA secondary structures for subgenotype A1 and subgenotype A2 were predicted,suggesting different base pairing patterns within the two subgenotypes of genotype A,specifically,in the HBV genetic region encoding the major hydrophilic loop.We observed that for subgenotype A1 specific pgRNA,nucleotide 358U base paired with 1738A and nucleotide 587G base paired with 607C.However in sharp contrast,in subgenotype A2 specific pgRNA,nucleotide 358U was opposite to nucleotide 588G,while 587G was opposite to 359U,hence precluding correct base pairing and thereby lesser stability of the stem structure.When the nucleotides at 358U and 587G were replaced with 358C and 587A respectively(as observed specifically in the PBL associated A2 sequences),these nucleotides base paired correctly with 588G and 359U,respectively.CONCLUSION The results of this study show that compartment specific mutations are associated with HBV subgenotype specific alterations in base pairing of the pgRNA,leading to compartment specific selection and preponderance of specific HBV subgenotype with unique mutational pattern.展开更多
文摘Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality.Hepatitis B virus(HBV)infection can be controlled by vaccines,antiviral treatment,and by interrupting transmission.Rare vaccine escape mutants are serious because they eliminate vaccine protection.Here,we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation.The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation.The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R,P120 Q,and Q129 P.The patient was successfully treated with entecavir.The epidemiological reasons for this subgenotype,which is extremely rare in Western Europe,were unclear.This case illustrates that second-generation vaccines are not always effective in a specific group of patients.
基金Supported by Fellowship and funds from University Grants Commission(UGC)Min.of Human Resource and Development,Govt.of India and Defence Research&Development Organi-zation(DRDO)(DRDO)+2 种基金Min.of Defence,Govt.of India(to Sibnarayan Datta)Indian Council of Medical Research(ICMR)Ministry of Health and Family Welfare(MoH FW)(to Runu Chakravarty)
文摘AIM To investigate the role of subgenotype specific RNA secondary structure in the compartment specific selection of hepatitis B virus(HBV)immune escape mutations.METHODS This study was based on the analysis of the specific observation of HBV subgenotype A1 in the serum/plasma,while subgenotype A2 with G145R mutation in the peripheral blood leukocytes(PBLs).Genetic variability found among the two subgenotypes was used for prediction and comparison of the full length pregenomic RNA(pgRNA)secondary structure and base pairings.RNA secondary structures were predicted for 37℃using the Vienna RNA fold server,using default parameters.Visualization and detailed analysis was done using RNA shapes program.RESULTS In this analysis,using similar algorithm and conditions,entirely different pgRNA secondary structures for subgenotype A1 and subgenotype A2 were predicted,suggesting different base pairing patterns within the two subgenotypes of genotype A,specifically,in the HBV genetic region encoding the major hydrophilic loop.We observed that for subgenotype A1 specific pgRNA,nucleotide 358U base paired with 1738A and nucleotide 587G base paired with 607C.However in sharp contrast,in subgenotype A2 specific pgRNA,nucleotide 358U was opposite to nucleotide 588G,while 587G was opposite to 359U,hence precluding correct base pairing and thereby lesser stability of the stem structure.When the nucleotides at 358U and 587G were replaced with 358C and 587A respectively(as observed specifically in the PBL associated A2 sequences),these nucleotides base paired correctly with 588G and 359U,respectively.CONCLUSION The results of this study show that compartment specific mutations are associated with HBV subgenotype specific alterations in base pairing of the pgRNA,leading to compartment specific selection and preponderance of specific HBV subgenotype with unique mutational pattern.
