scholarly journals The Hepatitis C Virus Nonstructural Protein 4B Is an Integral Endoplasmic Reticulum Membrane Protein

Virology ◽  
2001 ◽  
Vol 284 (1) ◽  
pp. 70-81 ◽  
Author(s):  
Thomas Hügle ◽  
Frauke Fehrmann ◽  
Elke Bieck ◽  
Michinori Kohara ◽  
Hans-Georg Kräusslich ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Membrane Protein ◽  
Nonstructural Protein ◽  
Endoplasmic Reticulum Membrane

scholarly journals Inhibitors of Endoplasmic Reticulum α-Glucosidases Potently Suppress Hepatitis C Virus Virion Assembly and Release

2010 ◽  
Vol 55 (3) ◽  
pp. 1036-1044 ◽  
Author(s):  
Xiaowang Qu ◽  
Xiaoben Pan ◽  
Jessica Weidner ◽  
Wenquan Yu ◽  
Dominic Alonzi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nonstructural Protein ◽  
Hcv Rna ◽  
Virion Assembly ◽  
Subsequent Degradation ◽  
Important Host ◽  
Antiviral Targets ◽  
Sugar Derivatives

ABSTRACTα-Glucosidases I and II are endoplasmic reticulum-resident enzymes that are essential for N-linked glycan processing and subsequent proper folding of glycoproteins. In this report, we first demonstrate that downregulation of the expression of α-glucosidase I, II, or both in Huh7.5 cells by small hairpin RNA technology inhibited the production of hepatitis C virus (HCV). In agreement with the essential role of α-glucosidases in HCV envelope glycoprotein processing and folding, treatment of HCV-infected cells with a panel of imino sugar derivatives, which are competitive inhibitors of α-glucosidases, did not affect intracellular HCV RNA replication and nonstructural protein expression but resulted in the inhibition of glycan processing and subsequent degradation of HCV E2 glycoprotein. As a consequence, HCV virion assembly and secretion were inhibited. In searching for imino sugars with better antiviral activity, we found that a novel imino sugar, PBDNJ0804, had a superior ability to inhibit HCV virion assembly and secretion. In summary, we demonstrated that glucosidases are important host factor-based antiviral targets for HCV infection. The low likelihood of drug-resistant virus emergence and potent antiviral efficacy of the novel glucosidase inhibitor hold promise for its development as a therapeutic agent for the treatment of chronic hepatitis C.

scholarly journals Mobility of the hepatitis C virus NS4B protein on the endoplasmic reticulum membrane and membrane-associated foci

2005 ◽  
Vol 86 (5) ◽  
pp. 1415-1421 ◽  
Author(s):  
Sarah N. Gretton ◽  
Annette I. Taylor ◽  
John McLauchlan
Keyword(s):  
Endoplasmic Reticulum ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Morphological Changes ◽  
Hcv Rna ◽  
Endoplasmic Reticulum Membrane ◽  
Structural Protein ◽  
Direct Role ◽  
Cellular Marker ◽  
Er Membrane

The hepatitis C virus (HCV) non-structural protein NS4B induces morphological changes in the endoplasmic reticulum (ER) membrane that may have a direct role in viral RNA replication. A chimeric GFP–NS4B fusion protein located to the ER membrane and to foci that were attached to the ER. These membrane-associated foci (MAFs) could be related to the membrane alterations observed in cells that replicate HCV RNA. The relationship of MAFs to pre-existing cellular structures is not known. Indirect immunofluorescence analysis demonstrated that they did not contain a cellular marker for vesicles, which have been implicated in the replication of other viruses. From photobleaching studies to examine diffusion of NS4B, the GFP-tagged protein had reduced mobility on MAFs compared with on the ER membrane. This slower mobility suggested that NS4B is likely to form different interactions on MAFs and the ER.

scholarly journals Core protein domains involved in hepatitis C virus-like particle assembly and budding at the endoplasmic reticulum membrane

2007 ◽  
Vol 9 (4) ◽  
pp. 1014-1027 ◽  
Author(s):  
Christophe Hourioux ◽  
Malika Ait-Goughoulte ◽  
Romuald Patient ◽  
Delphine Fouquenet ◽  
Fabienne Arcanger-Doudet ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Protein ◽  
Protein Domains ◽  
Endoplasmic Reticulum Membrane ◽  
Particle Assembly ◽  
Virus Like Particle

scholarly journals Role for TBC1D20 and Rab1 in Hepatitis C Virus Replication via Interaction with Lipid Droplet-Bound Nonstructural Protein 5A

2012 ◽  
Vol 86 (12) ◽  
pp. 6491-6502 ◽  
Author(s):  
I. Nevo-Yassaf ◽  
Y. Yaffe ◽  
M. Asher ◽  
O. Ravid ◽  
S. Eizenberg ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Replication ◽  
Lipid Droplet ◽  
Nonstructural Protein ◽  
Nonstructural Protein 5A

Mechanism of Zinc Ejection by Disulfiram in Nonstructural Protein 5A

2021 ◽  
Author(s):  
Ashfaq Ur Rehman ◽  
Guodong Zheng ◽  
Bozitao Zhong ◽  
Duan Ni ◽  
Jia-Yi Li ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nonstructural Protein ◽  
Structural Protein ◽  
Positive Strand ◽  
Positive Strand Rna ◽  
Nonstructural Protein 5A

Hepatitis C virus (HCV) is a notorious member of the enveloped, positive-strand RNA flavivirus family. Non-structural protein 5A (NS5A) plays a key role in HCV replication and assembly. NS5A is...

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