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Therapeutic potential of furin inhibitors for the chronic infection of hepatitis B virus.
In: Liver International, Jg. 33 (2013-09-01), Heft 8, S. 1230-1238
Online
academicJournal
Zugriff:
Background & Aims Hepatitis B e antigen ( HBeAg) is essential for the development of chronic hepatitis B virus ( HBV) infection. Furin, a proprotein convertase, plays a key role in processing of HBeAg precursor into maturated HBeAg. For these reasons, the therapeutic potential of furin inhibition for chronic HBV infection was studied. Methods The effects of furin inhibitor I (decanoyl- RVKR-chloromethylketone, CMK) and furin inhibitor II (hexa-D-arginine, D6R) on HBeAg secretion, the destination of unprocessed precursor and cellular secretory functions were comparatively investigated. Results CMK and D6R significantly decreased the supernatant level of HBeAg and increased the intracellular level of HBeAg precursor in HepG2.2.15 cells in vitro. The accumulated HBeAg precursor was not found to be retro-transported into the cytosol to inhibit HBV replication as expected, but was found to be expressed on the cell surface, where it may be more convenient to mediate host immune responses. Furthermore, these inhibitors at effective concentrations were not found to interfere with the maturations of albumin and prothrombin. Compared with CMK, D6R was suboptimal in effectiveness; however, D6R neither enhanced HBV replication through the accumulation of cytosolic HBcAg nor did it cause severe cell damage in an elongated safety analyses. Conclusion Furin inhibitors CMK and D6R reduce HBeAg secretion and increase cell surface expression of the HBeAg precursor in HepG2.2.15 cells. Novel furin inhibitors or modified forms of D6R may promote the reduction of immune tolerance and the elimination of infected hepatocytes in patients with chronic HBV infection. [ABSTRACT FROM AUTHOR]
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Therapeutic potential of furin inhibitors for the chronic infection of hepatitis B virus.
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Autor/in / Beteiligte Person: | Pang, Yan J. ; Tan, Xiao J. ; Li, Dong M. ; Zheng, Zi H. ; Lei, Rui X. ; Peng, Xiao M. |
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Zeitschrift: | Liver International, Jg. 33 (2013-09-01), Heft 8, S. 1230-1238 |
Veröffentlichung: | 2013 |
Medientyp: | academicJournal |
ISSN: | 1478-3223 (print) |
DOI: | 10.1111/liv.12185 |
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