Abstract
BackgroundHepatitis B virus (HBV) infection results in complications such as cirrhosis and hepatocellular carcinoma. Suppressing viral replication in chronic HBV carriers is an effective approach to controlling disease progression. Although antiviral compounds are available, we aimed to identify host factors that have a significant effect on viral replication efficiency.Methods and FindingsWe studied a group of hepatitis B carriers by associating serum viral load with their respective HBV genomes, and observed a significant association between high patient serum viral load with a natural sequence variant within the HBV enhancer II (Enh II) regulatory region at position 1752. Using a viral fragment as an affinity binding probe, we isolated a host DNA-binding protein belonging to the class of heterogeneous nuclear ribonucleoproteins—hnRNP K—that binds to and modulates the replicative efficiency of HBV. In cell transfection studies, overexpression of hnRNP K augmented HBV replication, while gene silencing of endogenous hnRNP K carried out by small interfering RNAs resulted in a significant reduction of HBV viral load.ConclusionThe evidence presented in this study describes a wider role for hnRNP K beyond maintenance of host cellular functions and may represent a novel target for pharmacologic intervention of HBV replication.
Highlights
Hepatitis B virus (HBV) infection is a serious public health problem in many parts of Asia and Africa that results in complications such as cirrhosis and cancer of the liver [1]
Antiviral compounds are available, we aimed to identify host factors that have a significant effect on viral replication efficiency
We studied a group of hepatitis B carriers by associating serum viral load with their respective HBV genomes, and observed a significant association between high patient serum viral load with a natural sequence variant within the HBV enhancer II (Enh II) regulatory region at position 1752
Summary
Hepatitis B virus (HBV) infection is a serious public health problem in many parts of Asia and Africa that results in complications such as cirrhosis and cancer of the liver [1]. Despite effective vaccination against HBV and available antiviral treatments [2,3,4,5,6,7], there remain an estimated 350 million hepatitis B carriers with a lifetime risk for developing cirrhosis and hepatocellular carcinoma, as many individuals infected during infancy remain infectious carriers for decades. Some drugs can suppress the multiplication of the virus, these drugs do not cure the patient of hepatitis B Another way of tackling the virus might become clear if it were known exactly how the virus interacts with the patient’s cells. In the laboratory, when the investigators increased the amount of this protein in cells infected with HBV, the virus multiplied more; when they decreased it, the virus multiplied less
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