Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor

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Title
Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor
Author(s)
I R Cho; M Oh; Sang Seok Koh; W Malilas; R Srisuttee; B H Jhun; S Pellegrint; S Y Fuchs; Y H Chung
Bibliographic Citation
International Journal of Molecular Medicine, vol. 29, no. 4, pp. 581-586
Publication Year
2012
Abstract
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.
Keyword
Hepatitis B virus XIFN-α receptorIFN-α signalingTyk2
ISSN
1107-3756
Publisher
Spandidos Publ Ltd
DOI
http://dx.doi.org/10.3892/ijmm.2012.879
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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