| Popis: |
Chronic hepatitis B is a major cause of liver failure and liver cancer, resulting in 600,000 annual deaths globally. Infection chronicity (and resultant liver disease) is determined by intrahepatic persistence of the viral covalently closed circular DNA (cccDNA), an episomal form that encodes all viral transcripts. Therefore, cccDNA is a key target for new treatments, with the ultimate aim of its elimination. While established cccDNA molecules are stable in resting hepatocytes, their fate in dividing cells is not well understood. Using highly-sensitive quantification assays, we observed a dramatic reduction in cccDNA levels, HBV-positive cell numbers, and cccDNA-dependent protein expression after each round of cell mitosis. These observations are consistent with a complete loss (as opposed to a dilution) of cccDNA in daughter cells. Our results thus show that HBV persistence can be efficiently overcome by inducing cell mitosis and justify therapeutic approaches that induce liver turnover (e.g. immune modulators) as an adjunct to achieve Hepatitis B cure. |
