1. Chimeric constructs between two hepatitis B virus genomes confirm transcriptional impact of core promoter mutations and reveal multiple effects of core gene mutations
- Author
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Karen Kwei, Alexander Hutter, Adrienne Tsai, Shuping Tong, Dina Gewaily, Jack R. Wands, Shigenobu Kawai, Jisu Li, and David R. Tong
- Subjects
Hepatitis B virus ,Genes, Viral ,Transcription, Genetic ,Core protein ,Biology ,DNA replication ,Virus Replication ,Genome ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Transcription (biology) ,Cell Line, Tumor ,Virology ,Gene expression ,Humans ,Trans-complementation ,Promoter Regions, Genetic ,Gene ,Core promoter ,Pregenomic RNA ,030304 developmental biology ,Genetics ,Naturally occurring mutations ,0303 health sciences ,030306 microbiology ,Viral Core Proteins ,RNA ,Promoter ,Molecular biology ,3. Good health ,Virus Shedding ,Viral replication ,chemistry ,DNA, Viral ,Mutation ,RNA, Viral ,Immature secretion ,DNA ,Reassortant Viruses ,Core gene - Abstract
Hepatitis B virus (HBV) clone 4B replicated much more efficiently than clone 2A of the same genotype. Introduction of its T1753C, A1762T, G1764A, and C1766T core promoter mutations into the 2A genome greatly enhanced genome replication and suppressed HBeAg expression. Here we show that these effects are mediated by transcriptional up regulation of pregenomic RNA and suppression of precore RNA. Analysis of chimeric constructs suggested that the 5′ end of the 2A core gene conferred higher level of pregenomic RNA, but less core protein and genome replication relative to the 4B sequence. Genome maturity of secreted virions was reduced by mutations present in the core protein of the 2A genome but enhanced by mutations found in the 4B core protein. The 4B core protein migrated faster than that of clone 2A. The possible links among the various phenotypes and the responsible mutations remain to be established.
- Published
- 2009
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