scholarly journals Identification of HNRNPK as Regulator of Hepatitis C Virus Particle Production

2015 ◽  
Vol 11 (1) ◽  
pp. e1004573 ◽  
Author(s):  
Marion Poenisch ◽  
Philippe Metz ◽  
Hagen Blankenburg ◽  
Alessia Ruggieri ◽  
Ji-Young Lee ◽  
...  

2018 ◽  
Vol 132 (1) ◽  
pp. jcs217042 ◽  
Author(s):  
Susan Lassen ◽  
Cordula Grüttner ◽  
Van Nguyen-Dinh ◽  
Eva Herker


2007 ◽  
Vol 81 (15) ◽  
pp. 8030-8040 ◽  
Author(s):  
Asako Murayama ◽  
Tomoko Date ◽  
Kenichi Morikawa ◽  
Daisuke Akazawa ◽  
Michiko Miyamoto ◽  
...  

ABSTRACT The JFH-1 strain of hepatitis C virus (HCV) is a genotype 2a strain that can replicate autonomously in Huh7 cells. The J6 strain is also a genotype 2a strain, but its full genomic RNA does not replicate in Huh7 cells. However, chimeric J6/JFH-1 RNA that has J6 structural-protein-coding regions and JFH-1 nonstructural-protein-coding regions can replicate autonomously and produce infectious HCV particles. In order to determine the mechanisms underlying JFH-1 RNA replication, we constructed various J6/JFH-1 chimeras and tested their RNA replication and virus particle production abilities in Huh7 cells. Via subgenomic-RNA-replication assays, we found that both the JFH-1 NS5B-to-3′X (N5BX) and the NS3 helicase (N3H) regions are important for the replication of the J6CF replicon. We applied these results to full-length genomic RNA replication and analyzed replication using Northern blotting. We found that a chimeric J6 clone with JFH-1 N3H and N5BX could replicate autonomously but that a chimeric J6 clone with only JFH-1 N5BX had no replication ability. Finally, we tested the virus production abilities of these clones and found that a chimeric J6 clone with JFH-1 N3H and N5BX could produce infectious HCV particles. In conclusion, the JFH-1 NS3 helicase and NS5B-to-3′X regions are important for efficient replication and virus particle formation of HCV genotype 2a strains.



2016 ◽  
Vol 97 (1) ◽  
pp. 69-81 ◽  
Author(s):  
Jessica Cottarel ◽  
Marie-Laure Plissonnier ◽  
Majlinda Kullolli ◽  
Sharon Pitteri ◽  
Sophie Clément ◽  
...  


2006 ◽  
Vol 81 (2) ◽  
pp. 629-638 ◽  
Author(s):  
MinKyung Yi ◽  
Yinghong Ma ◽  
Jeremy Yates ◽  
Stanley M. Lemon

ABSTRACT There is little understanding of mechanisms underlying the assembly and release of infectious hepatitis C virus (HCV) from cultured cells. Cells transfected with synthetic genomic RNA from a unique genotype 2a virus (JFH1) produce high titers of virus, while virus yields are much lower with a prototype genotype 1a RNA containing multiple cell culture-adaptive mutations (H77S). To characterize the basis for this difference in infectious particle production, we constructed chimeric genomes encoding the structural proteins of H77S within the background of JFH1. RNAs encoding polyproteins fused at the NS2/NS3 junction (“H-NS2/NS3-J”) and at a site of natural, intergenotypic recombination within NS2 [“H-(NS2)-J”] produced infectious virus. In contrast, no virus was produced by a chimera fused at the p7-NS2 junction. Chimera H-NS2/NS3-J virus (vH-NS2/NS3-J) recovered from transfected cultures contained compensatory mutations in E1 and NS3 that were essential for the production of infectious virus, while yields of infectious vH-(NS2)-J were enhanced by mutations within p7 and NS2. These compensatory mutations were chimera specific and did not enhance viral RNA replication or polyprotein processing; thus, they likely compensate for incompatibilities between proteins of different genotypes at sites of interactions essential for virus assembly and/or release. Mutations in p7 and NS2 acted additively and increased the specific infectivity of vH-(NS2)-J particles, while having less impact on the numbers of particles released. We conclude that interactions between NS2 and E1 and p7 as well as between NS2 and NS3 are essential for virus assembly and/or release and that each of these viral proteins plays an important role in this process.



2010 ◽  
Vol 85 (3) ◽  
pp. 1193-1204 ◽  
Author(s):  
T. Phan ◽  
A. Kohlway ◽  
P. Dimberu ◽  
A. M. Pyle ◽  
B. D. Lindenbach


2013 ◽  
Vol 87 (21) ◽  
pp. 11704-11720 ◽  
Author(s):  
L. Chatel-Chaix ◽  
M.-A. Germain ◽  
A. Motorina ◽  
E. Bonneil ◽  
P. Thibault ◽  
...  


2010 ◽  
Vol 84 (18) ◽  
pp. 9118-9127 ◽  
Author(s):  
Yukihiro Kushima ◽  
Takaji Wakita ◽  
Makoto Hijikata

ABSTRACT Hepatitis C virus (HCV) core protein forms the nucleocapsid of the HCV particle. Although many functions of core protein have been reported, how the HCV particle is assembled is not well understood. Here we show that the nucleocapsid-like particle of HCV is composed of a disulfide-bonded core protein complex (dbc-complex). We also found that the disulfide-bonded dimer of the core protein (dbd-core) is formed at the endoplasmic reticulum (ER), where the core protein is initially produced and processed. Mutational analysis revealed that the cysteine residue at amino acid position 128 (Cys128) of the core protein, a highly conserved residue among almost all reported isolates, is responsible for dbd-core formation and virus-like particle production but has no effect on the replication of the HCV RNA genome or the several known functions of the core protein, including RNA binding ability and localization to the lipid droplet. The Cys128 mutant core protein showed a dominant negative effect in terms of HCV-like particle production. These results suggest that this disulfide bond is critical for the HCV virion. We also obtained the results that the dbc-complex in the nucleocapsid-like structure was sensitive to proteinase K but not trypsin digestion, suggesting that the capsid is built up of a tightly packed structure of the core protein, with its amino (N)-terminal arginine-rich region being concealed inside.



2017 ◽  
Vol 4 (3) ◽  
pp. 405-417 ◽  
Author(s):  
Ursula Andreo ◽  
Ype P. de Jong ◽  
Margaret A. Scull ◽  
Jing W. Xiao ◽  
Koen Vercauteren ◽  
...  


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