Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor
| Autor: | Myung-Ju Oh, Sang Seok Koh, Byung Hak Jhun, Waraporn Malilas, Young-Hwa Chung, Il-Rae Cho, Ratakorn Srisuttee, Sandra Pellegrini, Serge Y. Fuchs |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Hepatitis B virus
viruses Down-Regulation IFN-α signaling Receptor Interferon alpha-beta Biology Transfection Cell Line Downregulation and upregulation Interferon Genetics medicine Humans Viral Regulatory and Accessory Proteins STAT1 RNA Messenger RNA Small Interfering Receptor skin and connective tissue diseases TYK2 Kinase Interferon-alpha General Medicine Articles Molecular biology digestive system diseases Tyk2 hepatitis B virus X HBx STAT1 Transcription Factor Cell culture biology.protein Trans-Activators sense organs Signal transduction medicine.drug IFN-α receptor Signal Transduction |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X 1107-3756 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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