Mechanisms of Hepatic Oncogenesis During Persistent Hepadna Virus Infection
One of the earliest events following penetration and uncoating of hepadna viruses is the conversion of the viral DNA into a covalently closed circular (CCC) molecule , (Figure 30.1). The CCC DNA accumulates in the nucleus and is believed to serve as the template for synthesis of viral RNAs, including pregenome RNA and mRNA encoding viral proteins. The pregenome RNAs are packaged into particles with viral core protein in the cytoplasm and reverse transcription occurs, leading to the production of a full-length viral DNA minus strand . Plus strand DNA synthesis begins approximately 250 bp from the 5′ end of the minus strand and is primed by an RNA oligonucleotide from the 5′ end of the RNA pregenome . After plus strand DNA synthesis reaches the 5′ end of the minus DNA strand, it “jumps the gap” to the 3′ end of the minus DNA strand, resulting in circularization of the minus strand DNA. For reasons that are unclear, virions are formed and secreted before plus strand DNA synthesis is completed, and therefore, DNA molecules in virions are open circular and contain a single strand region. Completion of the viral DNA plus strand is an early event after the virus infects a permissive host cell (Figure 30.1). Transcription and translation of viral genes proceeds in an undirectional fashion, utilizing all three translational reading frames as the result of the overlap of viral genes  (Figure 30.2A).
KeywordsMinus Strand Woodchuck Hepatitis Virus Covalently Close Circular Recessive Oncogene Hepadna Virus
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