Inhibition of cellular proteasome activities enhances hepadnavirus replication in an HBX-dependent manner.
The X protein (HBX) of the hepatitis B virus (HBV) is not essential for the HBV life cycle in vitro but is important for productive infection in vivo. Our previous study suggests that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. With the woodchuck model, we demonstrated that the X-deficient mutants of woodchuck hepatitis virus (WHV) are not completely replication defective, possibly behaving like attenuated viruses. In the present study, we analyzed the effects of the proteasome inhibitors on the replication of wild-type and X-negative HBV and WHV. Recombinant adenoviruses or baculoviruses expressing replicating HBV or WHV genomes have been developed as a robust and convenient system to study viral replication in tissue culture. In cells infected with either the recombinant adenovirus-HBV or baculovirus-WHV, the replication level of the X-negative construct was about 10% of that of the wild-type virus. In the presence of proteasome inhibitors, the replication of the wild-type virus was not affected, while the replication of the X-negative virus of either HBV or WHV was enhanced and restored to the wild-type level. Our data suggest that HBX affects hepadnavirus replication through a proteasome-dependent pathway.
Zhang
Zhensheng
Z
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Protzer
Ulrike
U
Hu
Zongyi
Z
Jacob
James
J
Liang
T Jake
TJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D020013:Calcium Signaling; D003546:Cysteine Endopeptidases; D015613:Hepadnaviridae / Q000502:physiology*; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics / Q000502:physiology; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009154:Mutation; D046988:Proteasome Endopeptidase Complex; D011995:Recombination, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication
D009097:Multienzyme Complexes; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex