Viral Transcription

After infection of a hepatocyte, viral genome is transported to the nucleus and then converted to a covalently closed, circular dsDNA, called cccDNA.

All transcription is completed on the negative strand DNA.

The P protein attached to the minus strand and the RNA oligonucleotides at the 5' end of the plus strand are removed.  Gaps are filled and the ends of the DNA strands are closed. Host repair enzymes are believed to carry out these processes.

The resulting cccDNA does not integrate into the host genome nor does it replicate as an episome. 

Only one strand (negative strand) of the cccDNA is transcribed by cellular RNA polymerase II. Several mRNAs are produced. 4 different promoters lead to 4 unspliced transcripts of 3.5kb, 2.4, 2.1, and 0.7kb  in length. The 3.5 kb mRNA is slightly larger than the genome, due to repeat sequences.  All mRNAs end at the same poly(A) site.

RNA transcripts are capped and polyadenylated. 

Transcription of viral DNA is most efficient in hepatocytes because some of the promoters require transcription factors such as hepatocyte nuclear factor 1, for optimal function. In addition, there are two known enhancers that work best in hepatocytes.