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

Cho,Il-Rae; Oh,Myungju; Koh,Sang  Seok; Malilas,Waraporn; Srisuttee,Ratakorn; Jhun,Byung Hak; Pellegrini,Sandra; Fuchs,Serge  Y.; Chung,Young-Hwa

doi:10.3892/ijmm.2012.879

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

Authors:
- Il-Rae Cho
- Myungju Oh
- Sang Seok Koh
- Waraporn Malilas
- Ratakorn Srisuttee
- Byung Hak Jhun
- Sandra Pellegrini
- Serge Y. Fuchs
- Young-Hwa Chung
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Affiliations: WCU Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735, Republic of Korea
Published online on: January 3, 2012 https://doi.org/10.3892/ijmm.2012.879
Pages: 581-586

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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.

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