Precore/core mutations of hepatitis B virus genotype D arising in different states of infection.
PMID: 35415256
2022
Clinical and experimental hepatology
Introduction: In a study conducted in the Korean population, the five HBcAg mutations P5H/L/T, E83D, I97F/L, L100I, and Q182K/Stop were significantly more frequent in subjects with chronic hepatitis and cirrhosis.
Conformational Plasticity of Hepatitis B Core Protein Spikes Promotes Peptide Binding Independent of the Secretion Phenotype.
Result: Fitting of the isotherms gave a stoichiometry of n = 0.5 for P5T-HBc, WT-HBc and F97L-HBc, suggesting that each HBc dimer in the capsid bound one peptide.
Result: While L60V-HBc, WT-HBc and F97L-HBc had similar transition temperatures between 91 C and 95 C, the transition temperature of P5T-HBc was much lower (TM = 86 C), showing that the mutation P5T weakens the stability of the whole capsid substantially.
Discussion:
Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97.
8Discussion: However, neither the mutants (P5T and L60V) nor wt HBc-CLPs with bound peptides show Phe-97 is in ""conformation 2"" suggesting that flipping of Phe-97 is dispensable for conformational changes at the tips of the spikes."
Abstract: Similar changes occur in mutants with low secretion phenotypes (P5T and L60V) and in a mutant with a pre-mature secretion phenotype (F97L).
Introducti
Discussion: It is hard to reconcile how a pocket factor that is mimicked by TX100 could act as maturation signal considering that we do not see any major differences in the structural mode of binding in naturally occurring mutants (F97L, P5T and L60V) with different secretion phenotypes.
Naturally occurring core protein mutations compensate for the reduced replication fitness of a lamivudine-resistant HBV isolate.
Discussion: It has been reported that the P5T mutation of HBcAg is common in HBV-related acute-on-chronic liver failure (ACLF) patients.
Discussion: Moreover, P5T mutation enhanced the EIA signal of capsid in the native gel assay, indicating that P5T may promote capsid assembly and the subsequent pgRNA encapsidation.
Discussion: The mechanistic link between P5T mutation and CHB exacerbation including ACLF remains elusive, but may be related to the enhanced virus replication and/or
Persistence of Hepatitis B Virus DNA and the Tempos between Virion Secretion and Genome Maturation in a Mouse Model.
3Introduction: Interestingly, while a single HBc mutation L60V or P5T displayed a low-level secretion phenotype, a single mutation P130T led to a ""hypermaturation phenotype"" characterized by an increased abundance of both intracellular and extracellular fully mature full-length RC DNA."
Introduction: Both P130T and P5T could compensate for or rescue the immature secretion phenotype of mutant I97L.
Introduction: In addition to this HBc 97L mutation, HBc P130T and P5T mutations were found frequently in patients.
The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease.
PMID: 30406036
2018
Frontiers in cellular and infection microbiology
Introduction: Furthermore, five HBcAg mutations identified in a Korean population, P5H/L/T, E83D, I97F/L, L100I, and Q182K/Stop, were shown to be significantly enriched in HCC patients compared with patients at earlier disease stages, including those with cirrhosis and chronic hepatitis (Kim et al.,).
Introduction: Similarly, a study of an Indian population showed that HBcAg residue 5 mutations P5H/L/T or P5R were found more frequently in HCC pati
Upregulation of endoplasmic reticulum stress and reactive oxygen species by naturally occurring mutations in hepatitis B virus core antigen.
PMID: 25828947
2015
The Journal of general virology
Abstract: Here, we found that the naturally occurring mutations P5T/H/L of the HBV core antigen induced ER stress.
Novel point and combo-mutations in the genome of hepatitis B virus-genotype D: characterization and impact on liver disease progression to hepatocellular carcinoma.
8Discussion: Interestingly, the most frequently observed naturally occurring core protein mutation found in CHB and also in HCC patients I97L or F97L which is associated with ""immature virion secretion"" was completely absent in Indian patients with HBV-genotype D while among the ""low secretion core variants"" such as P5T/A/S, a new variant P5R was noted with high frequency in HBV-genotype D related HCC in previous Indian study."
Naturally occurring precore/core region mutations of hepatitis B virus genotype C related to hepatocellular carcinoma.
Result: Five mutations in the C region (C-P5H/L/T,
Result: Notably, the following 4 of 5 HCC-related C mutations, C-P5H/L/T, C-E83D, C-I97F/L and C-L100I, were located at M2RR (one at aa 1-20 and three at aa 81-105.
Discussion: Of the five mutations in the C region positively related to HCC found in this study, the following three types, C-P5H/L/T, C-E83D, and C-I97F/L were introduced by other studies.
Chimeric constructs between two hepatitis B virus genomes confirm transcriptional impact of core promoter mutations and reveal multiple effects of core gene mutations.
Discussion: In contrast, a P5T mutation impairs virion secretion when present alone and restores wild-type secretion phenotype when combined with the I97L mutation.
HBV mutation literature information.
PMID: 
2022
Clinical and experimental hepatology
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