title: Tracking the naturally occurring mutations across the full-length genome of hepatitis B virus of genotype D in different phases of chronic e-antigen-negative infection.
abstract: Hepatitis B e-antigen (HBeAg)-negative chronic HBV infection is highly prevalent in several parts of the world, including India, with the clinical spectrum ranging from inactive carrier (IC) state to chronic 'e-negative' hepatitis B (CHB) and culminating in advanced liver disease such as cirrhosis (LC). The present study has for the first time investigated the natural diversity of HBV belonging to genotype D in treatment-naïve Indian patients representing the above phases of HBeAg-negative infection to identify candidate mutations associated with each disease state. Studies of full-length HBV/D sequences revealed that the progressive accumulation and persistence of mutations in basal core promoter, negative regulatory element, Pre-core region, the B- and T-cell epitopes of X protein as well as deletions in the PreS region contribute significantly to disease progression from IC through CHB to LC. In addition, the development of CHB was associated with a significant increase in viral variants characterized by mutations in enhancer II, preS1 promoter, T-cell epitope of core and B-cell epitope region of PreS1. While few of the mutations were previously reported in the context of HBV genotypes B and C, others had not been documented before. Our results thus highlight a distinct pattern of mutation in HBV/D that may help in predicting clinical outcomes of HBeAg-negative infection and have implications for better clinical management of the patients.
authors: Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors: S
authors: S
authors: Ghosh
authors: R K
authors: RK
authors: Mondal
authors: P
authors: P
authors: Banerjee
authors: M
authors: M
authors: Nandi
authors: S
authors: S
authors: Sarkar
authors: K
authors: K
authors: Das
authors: A
authors: A
authors: Santra
authors: S
authors: S
authors: Banerjee
authors: A
authors: A
authors: Chowdhury
authors: S
authors: S
authors: Datta
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002353:Carrier State / Q000821:virology*; D018450:Disease Progression; D005260:Female; D005814:Genes, Viral; D016679:Genome, Viral; D005838:Genotype; D006513:Hepatitis B e Antigens; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010802:Phylogeny; D014759:Viral Envelope Proteins; D055815:Young Adult
chemical_list: D006513:Hepatitis B e Antigens; D014759:Viral Envelope Proteins