Turnover of hepatitis B virus X protein is facilitated by Hdj1, a human Hsp40/DnaJ protein.
Hepatitis B virus X (HBX) protein is required for the productive infection of hepatitis B virus (HBV) in vivo and implicated in the development of hepatocellular carcinoma. We have previously shown that hTid-1 and Hdj1, the human Hsp40/DnaJ chaperone proteins, bind the HBV core protein and inhibit viral replication in cell culture system. Here, we report evidences to suggest that HBX is the major target of Hdj1 in the inhibition of HBV replication. Expression of Hdj1 in cultured human hepatoma HepG2 cells facilitated degradation of HBX by the proteasome pathway, and thereby inhibited replication of the wild-type HBV as well as that of the HBX-deficient mutant virus rescued by HBX supplied in trans. Mutational analyses indicated that J domain of Hdj1 is required for the process. These results might provide a molecular basis for the antiviral effect of cellular chaperones.
Sohn
Sook-Young
SY
School of Life Sciences and Biotechnology, Korea University, Sungbuk, Seoul, Republic of Korea.
Kim
Jung-Hwan
JH
Baek
Kyung-Won
KW
Ryu
Wang-Shick
WS
Ahn
Byung-Yoon
BY
D045744:Cell Line, Tumor; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000502:physiology; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication
C494647:DNAJB1 protein, human; D050956:HSP40 Heat-Shock Proteins; D015534:Trans-Activators; D025801:Ubiquitin; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D046988:Proteasome Endopeptidase Complex