Miktari olculdugunde intrahepatik cccDNA
A complete sterilising cure with undetectable HBsAg in serum and eradication of intrahepatic cccDNA
, as well as integrated cccDNA
, is not presently feasible.
Roggendorf, "Current status of immunomodulatory therapy in chronic hepatitis B, fifty years after discovery of the virus: Search for the "magic bullet" to kill cccDNA
," Antiviral Research, vol.
Keza onceki yillarda DNA hibridizasyon teknikleri kullanilarak gerceklestirilen molekuler biyolojik calismalar OBI pozitif bireylerin karaciger dokusunda replikasyon aracisi olarak gorev yapan pregenomik RNA (RNA intermediate, pgRNA) ile cccDNA
'nin tek bir hucredeki kopya sayisinin olculmesi icin yeterli duyarliliga sahip degillerdi.
Although new drugs to prevent cccDNA
formation and HBV life cycle events such as capsid assembly and HBeAg expression may further improve outcomes, they still may not be curative without better host defenses.
Concomitantly, intracellular HBV replication markers at day 10 were analyzed, and qPCR analysis revealed more than 50% reduction of cccDNA
and intracellular HBV-DNA after IFNa pretreatment (Figure 1(d)).
We quantified HBV cccDNA
in FFPE tumor tissues of HCC patients as described previously (23).
Conversion of viral genome to a covalently closed circular DNA (cccDNA
), which is formed in the nuclei of infected hepatocytes within the first 24h following virus inoculation and forming of a minichromosome after binding to proteins, is the molecular basis of persistence13.
episome is the transcriptional template for HBV messenger RNA transcripts that encode viral structural and NS proteins and the pregenomic RNA template for reverse transcription and synthesis of the viral genome .
In addition, nucleoside analogues may also interfere with de novo infection of hepatocytes by hindering the transformation of relaxed circular DNA into cccDNA
Guerrieri et al., "IFN-a inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA
minichromosome," The Journal of Clinical Investigation, vol.
DNA extracts were treated with Plasmid-Safe ATP-Dependent DNase (Epicenter Biotechnologies, Madison, WI, USA) to selectively hydrolyze linear double-stranded chromosomal DNA while leaving HBV covalently closed circular DNA (cccDNA
In the context of a low viral load (below 2000 IU/mL), if the patient does not present signs of hepatic damage such as increased necroinflammatory activity, fibrosis and/or increase of ALT, we can take into account a potential mutation affecting viral fitness, (7) which would lead to a relatively low replication rate of the virus, a decreased virulence and could contribute to increasing the patient's life expectancy and his chance of being at some point enrolled in a therapeutic trial, for treatment with a new molecule which would facilitate viral clearance (including clearance of cccDNA
from circulating monocytes).
In the process of HBV replication, the pregenomic RNA, which is transcribed from covalently closed circular DNA (cccDNA
), is reverse-transcribed by the polymerase protein of HBV.
It achieves this through covalently closed circular DNA (cccDNA
) that forms the template upon which viral particles can be replicated.