User:Sonam Sapra/sandbox

Final Article:

What is cccDNA:

cccDNA (covalently closed circular DNA) is present in viruses that infect cells. Hepatitis B is a disease that is caused by the hepatitis B virus, also known as HBV. Once HBV enters a cell, it undergoes various processes that convert its RC-DNA into cccDNA. This process ultimately covalently joins the positive and negative strands of the RC-DNA to form a circular, supercoiled molecule of DNA, now known as cccDNA. cccDNA exists as an episomal chromosome, therefore it is genetic material that is independent from the rest of the genetic material already present in the infected cell. This results in a more stable viral genome. This stability ensures that the cccDNA can remain in the cell where it functions as a template for viral gene transcription, meaning it is a template for various viral mRNAs.

Structure of cccDNA:

The structure of cccCDNA, which is circular and supercoiled, is important for its function. Primarily, it confers its ability to remain in the nucleus of the cell for a long period of time. This is important because it allows transcription to continue occurring. Additionally, nucleosome positioning on cccDNA is important. When cccDNA is wrapped around many nucleosomes it is inactive. However, when only parts of the cccDNA are wrapped around nucleosomes it is active, therefore viral RNA transcription can occur.  The positioning of these nucleosomes is not random; they are placed at DNA sequence specific sites depending on if transcription of these sites should or should not occur, therefore the wrapping around of nucleosomes is a form of transcription regulation.

Role that cccDNA plays in Hepatitis B:

HBV infects hepatocytes, the main cell type in the liver. Once inside of the hepatocyte, its RC-DNA converts into cccDNA, which proceeds to accumulate in the nucleus. Unless purposely eliminated, cccDNA can remain inside of the nucleus for the entirety of the hepatocytes lifespan. Consequently, as cccDNA functions as the template for viral RNA transcription, copies of the virus will be continuously made in the hepatocyte, thus perpetuating Hepatitis B. Those infected with HBV will often undergo various treatments such as antiviral therapy, but will still have a recurrence of Hepatitis B.  This reoccurrence is due to the cccDNA persisting in the system. To effectively get rid of Hepatitis B, a system must be cleared of cccDNA.

The Influence of Epigenetics on cccDNA:

Epigenetics involves genetic control and regulation through various mechanisms that do not involve changing the actual DNA sequence. Epigenetics is not exclusive to Eukaryotic DNA, as cccDNA has been found to undergo epigenetic regulation. cccDNA is organized into the “beads on a string” structure. Essentially there are nucleosomes consisting of histones, separated by a stretch of DNA. There are various ways in which HBV cccDNA is regulated epigenetically, as it is associated with numerous chromatin and non-chromatin proteins in the nucleus of infected hepatocytes. This regulation plays a role in the transcriptional activity of cccDNA. It undergoes both acetylation, specifically on histones H3 and H4 and DNA methylation at CpG islands. Additionally, there is an HBV core protien that binds to the cccDNA, which will decrease how far apart the nucleosomes are spaced from each other by 20bp. Nucleosome positioning also regulates transcription. Ultimately, epigenetic regulation controls the transcriptional activity of cccDNA. Subsequently, antiviral therapy can use epigenetics to suppress the HBV virus.