Strain-dependent viral dynamics and virus-cell interactions in a novel in vitro system supporting the life cycle of blood-borne hepatitis C virus

Hepatology ◽  
2009 ◽  
Vol 50 (3) ◽  
pp. 689-696 ◽  
Author(s):  
Hussein Hassan Aly ◽  
Yue Qi ◽  
Kimie Atsuzawa ◽  
Nobuteru Usuda ◽  
Yasutsugu Takada ◽  
...  
2007 ◽  
Vol 81 (16) ◽  
pp. 8374-8383 ◽  
Author(s):  
Christopher T. Jones ◽  
Catherine L. Murray ◽  
Dawnnica K. Eastman ◽  
Jodie Tassello ◽  
Charles M. Rice

ABSTRACT Hepatitis C virus (HCV) infection is a global health concern affecting an estimated 3% of the world's population. Recently, cell culture systems have been established, allowing recapitulation of the complete virus life cycle for the first time. Since the HCV proteins p7 and NS2 are not predicted to be major components of the virion, nor are they required for RNA replication, we investigated whether they might have other roles in the viral life cycle. Here we utilize the recently described infectious J6/JFH chimera to establish that the p7 and NS2 proteins are essential for HCV infectivity. Furthermore, unprocessed forms of p7 and NS2 were not required for this activity. Mutation of two conserved basic residues, previously shown to be important for the ion channel activity of p7 in vitro, drastically impaired infectious virus production. The protease domain of NS2 was required for infectivity, whereas its catalytic active site was dispensable. We conclude that p7 and NS2 function at an early stage of virion morphogenesis, prior to the assembly of infectious virus.


2013 ◽  
Vol 125 (9) ◽  
pp. 439-448 ◽  
Author(s):  
Yuan-Lung Cheng ◽  
Keng-Hsueh Lan ◽  
Wei-Ping Lee ◽  
Szu-Han Tseng ◽  
Li-Rong Hung ◽  
...  

HCV (hepatitis C virus) infection affects an estimated 180 million people in the world's population. Adverse effects occur frequently with current standard treatment of interferon and ribavirin, while resistance of new direct anti-viral agents, NS3 protease inhibitors, is a major concern because of their single anti-HCV mechanism against the viral factor. New anti-viral agents are needed to resolve the problems. Amiodarone, an anti-arrhythmic drug, has recently been shown to inhibit HCV infection in vitro. The detailed mechanism has yet to be clarified. The aim of the present study was to elucidate the molecular mechanism of the inhibitory effect of amiodarone on HCV life cycle. The effect of amiodarone on HCV life cycle was investigated in Huh-7.5.1 cells with HCVcc (cell culture-derived HCV), HCVpp (HCV pseudoviral particles), sub-genomic replicons, IRES (internal ribosomal entry site)-mediated translation assay, and intracellular and extracellular infectivity assays. The administration of amiodarone appeared to inhibit HCV entry independent of genotypes, which was attributed to the down-regulation of CD81 receptor expression. The inhibitory effect of amiodarone also manifested in the HCV assembly step, via the suppression of MTP (microsomal triacylglycerol transfer protein) activity. Amiodarone revealed no effects on HCV replication and translation. With the host factor-targeting characteristics, amiodarone may be an attractive agent for the treatment of HCV infection.


FEBS Journal ◽  
2007 ◽  
Vol 274 (18) ◽  
pp. 4705-4718 ◽  
Author(s):  
Morgane Régeard ◽  
Charlotte Lepère ◽  
Maud Trotard ◽  
Philippe Gripon ◽  
Jacques Le Seyec

2017 ◽  
Vol 66 (1) ◽  
pp. S322
Author(s):  
N. Mejer ◽  
A. Galli ◽  
U. Fahnøe ◽  
S. Ramirez ◽  
T. Benfield ◽  
...  

2003 ◽  
Vol 58 (3) ◽  
pp. 199-208 ◽  
Author(s):  
Tin-Yun Ho ◽  
Shih-Lu Wu ◽  
I-Lu Lai ◽  
Ken-Sheng Cheng ◽  
Shung-Te Kao ◽  
...  

2010 ◽  
Vol 87 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Itxaso Bellón-Echeverría ◽  
Alberto José López-Jiménez ◽  
Pilar Clemente-Casares ◽  
Antonio Mas

2012 ◽  
Vol 56 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Hussein H. Aly ◽  
Kunitada Shimotohno ◽  
Makoto Hijikata ◽  
Tsukasa Seya

FEBS Letters ◽  
2008 ◽  
Vol 583 (2) ◽  
pp. 277-280 ◽  
Author(s):  
Alexander V. Ivanov ◽  
Vera L. Tunitskaya ◽  
Olga N. Ivanova ◽  
Vladimir A. Mitkevich ◽  
Vladimir S. Prassolov ◽  
...  

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