Host heterogeneous ribonucleoprotein K (hnRNP K) as a potential target to suppress hepatitis B virus replication.
BACKGROUND
Hepatitis 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.


RESULTS
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. 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.


CONCLUSIONS
The 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.
Ng
Lisa F P
LF
Genome Institute of Singapore, Singapore.
Chan
Marieta
M
Chan
Soh-Ha
SH
Cheng
Paul Chung-Pui
PC
Leung
Eastwood Hon-Chiu
EH
Chen
Wei-Ning
WN
Ren
Ee-Chee
EC
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000378:metabolism*; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014779:Virus Replication
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K