Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal             transduction by downregulation of type I IFN receptor.
We have previously shown that hepatitis B virus (HBV) protein X (HBX), a regulatory protein of HBV, activates Stat1, leading to type I interferon (IFN) production. Type I IFN secreted from HBX-expressing hepatic cells enforces antiviral signals through its binding to the cognate type I IFN receptor. We therefore investigated how cells handle this detrimental situation. Interestingly, compared to Chang cells stably expressing an empty vector (Chang-Vec), Chang cells stably expressing HBX (Chang-HBX) showed lower levels of IFN-α receptor 1 (IFNAR1) protein, a subunit of type I IFN receptor. The levels of IFNAR1 transcripts detected in Chang-HBX cells were lower than the levels in Chang-Vec cells, indicating that HBX regulates IFNAR1 at the transcriptional level. Moreover, we observed that HBX induced the translocation of IFNAR1 to the cytoplasm. Consistent with these observations, HBX also downregulated Tyk2, which is required for the stable expression of IFNAR1 on the cell surface. Eventually, Chang-HBX cells consistently maintained a lower level of IFNAR1 expression and displayed no proper response to IFN-α, while Chang-Vec cells exhibited a proper response to IFN-α treatment. Taken together, we propose that HBX downregulates IFNAR1, leading to the avoidance of extracellular IFN-α signal transduction.
WCU Department of Cogno-Mechatronics Engineering, Pusan National                     University, Busan 609-735, Republic of Korea.
Il-Rae
IR
Cho
Myungju
M
Oh
Sang Seok
SS
Koh
Waraporn
W
Malilas
Ratakorn
R
Srisuttee
Byung Hak
BH
Jhun
Sandra
S
Pellegrini
Serge Y
SY
Fuchs
Young-Hwa
YH
Chung
D002460:Cell Line; D015536:Down-Regulation; D006515:Hepatitis B virus; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053634:TYK2 Kinase / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
C507964:IFNAR1 protein, human; D016898:Interferon-alpha; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D053633:Receptor, Interferon alpha-beta; D053634:TYK2 Kinase; C070139:TYK2 protein, human