title: Hepatitis B "e" antigen-mediated inhibition of HBV replication fitness and transcription efficiency in vitro.
abstract: A mutation at nucleotide 1896 (G1896A) is the most common cause for the loss of HBeAg. In contrast to clinical data, cell culture studies report a high-replicating phenotype for the G1896A mutant. Differences between the wild-type and the G1896A mutant in early steps of HBV replication including the synthesis of pre-genomic RNA and transcripts have not been investigated. The G1896A mutant is associated with higher replication fitness, transcription efficiency and higher levels of secreted HBsAg than the wild-type. Interestingly, trans-complementation of the G1896A mutant with HBeAg lowers the replication fitness and transcriptionefficiency to levels comparable to that of the wild-type. Our results highlight the role of HBeAg in modulating the early steps in HBV replication. In sum, our findings highlight the role of HBeAg in regulating hepatitis B virus replication fitness and transcription efficiency and new insights on the early steps of replication in the G1896A mutant.
authors.affiliation: Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Samal
authors.affiliation: Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Kandpal
authors.affiliation: Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India. Electronic address: vperumal@bioschool.iitd.ac.in.
authors.forename: Perumal
authors.initials: P
authors.lastname: Vivekanandan
mesh_terms: D002460:Cell Line; D017353:Gene Deletion; D005816:Genetic Complementation Test; D006513:Hepatitis B e Antigens / Q000235:genetics* / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D017354:Point Mutation; D014158:Transcription, Genetic; D019562:Viral Load; D014779:Virus Replication
chemical_list: D006513:Hepatitis B e Antigens
keywords: G1896A; HBV; HBeAg; HBsAg; Pre-core mutation; Replication fitness; Transcription efficiency; Virion secretion