Abstract
Human hepatitis B virus (HBV) infection remains a serious health problem worldwide. However, the mechanism for the maintenance of HBV in a latent state within host cells remains unclear. Here, using single-cell RNA sequencing analysis, we identified four genes linked to the maintenance of HBV in a liver cell line expressing HBV RNA at a low frequency. These genes included DOCK11 and DENND2A, which encode small GTPase regulators. In primary human hepatocytes infected with HBV, knockdown of these two genes decreased the amount of both HBV DNA and covalently closed circular DNA to below the limit of detection. Our findings reveal a role for DOCK11 and DENND2A in the maintenance of HBV.
Highlights
It is estimated that 350 million people worldwide are chronic carriers of hepatitis B virus (HBV), which is a principal cause of chronic liver disease
We examined the effect of knockdown of DOCK11 and DENND2A on HBV DNA and closed circular DNA (cccDNA) levels in long-term cultures of Primary human hepatocyte (PHH) after HBV infection
We have described above the inhibition of cccDNA formation in PHHs infected with HBV after treatment with shRNA
Summary
It is estimated that 350 million people worldwide are chronic carriers of hepatitis B virus (HBV), which is a principal cause of chronic liver disease. More than 780,000 people die every year due to the complications of hepatitis B infection, including cirrhosis and liver cancer [1]. HBV carriers are much more likely to develop liver cancer than uninfected individuals. HBV exists as a small, partially double-stranded DNA genome. The partially double-stranded genome is converted into covalently closed circular DNA (cccDNA) in the nucleus [2]. HBV can be maintained in a latent state in cells as stably inactivated cccDNA. Impairment of the immune system by chemotherapy or hematopoietic stem cell transplantation can induce HBV reactivation. Interactions between the host immune system and the virus influence the rate of development of advanced liver
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