scholarly journals Protein−Protein Interactions:  Modeling the Hepatitis C Virus Ion Channel p7

2006 ◽  
Vol 49 (2) ◽  
pp. 648-655 ◽  
Author(s):  
George Patargias ◽  
Nicole Zitzmann ◽  
Raymond Dwek ◽  
Wolfgang B. Fischer
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Ion Channel ◽  
Protein Interactions ◽  
Protein Protein Interactions

scholarly journals Mutations in hepatitis C virus p7 reduce both the egress and infectivity of assembled particles via impaired proton channel function

2013 ◽  
Vol 94 (10) ◽  
pp. 2236-2248 ◽  
Author(s):  
Matthew J. Bentham ◽  
Toshana L. Foster ◽  
Christopher McCormick ◽  
Stephen Griffin
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Interactions ◽  
Particle Production ◽  
Specific Protein ◽  
Proton Channel ◽  
Efficient Production ◽  
Channel Activity ◽  
Protein Protein Interactions ◽  
Genotype 1B

Hepatitis C virus (HCV) p7 protein is critical for the efficient production of infectious virions in culture. p7 undergoes genotype-specific protein–protein interactions as well as displaying channel-forming activity, making it unclear whether the phenotypes of deleterious p7 mutations result from the disruption of one or both of these functions. Here, we showed that proton channel activity alone, provided in trans by either influenza virus M2 or genotype 1b HCV p7, was both necessary and sufficient to restore infectious particle production to genotype 2a HCV (JFH-1 isolate) carrying deleterious p7 alanine substitutions within the p7 dibasic loop (R33A, R35A), and the N-terminal trans-membrane region (N15 : C16 : H17/AAA). Both mutations markedly reduced mature p7 abundance, with those in the dibasic loop also significantly reducing levels of mature E2 and NS2. Interestingly, whilst M2 and genotype 1b p7 restored the same level of intracellular infectivity as JFH-1 p7, supplementing with the isogenic protein led to a further increase in secreted infectivity, suggesting a late-acting role for genotype-specific p7 protein interactions. Finally, cells infected by viruses carrying p7 mutations contained non-infectious core-containing particles with densities equivalent to WT HCV, indicating a requirement for p7 proton channel activity in conferring an infectious phenotype to virions.

scholarly journals Different Domains of CD81 Mediate Distinct Stages of Hepatitis C Virus Pseudoparticle Entry

2006 ◽  
Vol 80 (10) ◽  
pp. 4940-4948 ◽  
Author(s):  
Claire Bertaux ◽  
Tatjana Dragic
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Interactions ◽  
Target Cells ◽  
Protein Protein Interactions ◽  
Molecular Events ◽  
Virus Complex ◽  
Large Extracellular Loop ◽  
Specific Factors ◽  
Intracellular Domains

ABSTRACT The CD81 tetraspanin was first identified as a hepatitis C virus (HCV) receptor by its ability to bind the soluble ectodomain of envelope glycoprotein E2 (sE2). More recently, it has been suggested that CD81 is necessary but not sufficient for HCV entry into target cells. Here we present further evidence that putative human hepatocyte-specific factors act in concert with CD81 to mediate sE2 binding and HCV pseudoparticle (HCVpp) entry. Moreover, we show that CD81-mediated HCVpp entry entails E2 binding to residues in the large extracellular loop as well as molecular events mediated by the transmembrane and intracellular domains of CD81. The concept that CD81 receptor function progresses in stages is further supported by our finding that anti-CD81 monoclonal antibodies inhibit HCVpp entry by different mechanisms. The half-life of CD81-HCVpp binding was determined to be approximately 17 min, and we propose that binding is followed by CD81 oligomerization, partitioning into cholesterol-rich membrane domains, or other, lateral protein-protein interactions. This results in the formation of a receptor-virus complex that undergoes endocytosis and pH-dependent membrane fusion.

scholarly journals Characterization of Nonstructural Protein Membrane Anchor Deletion Mutants Expressed in the Context of the Hepatitis C Virus Polyprotein

2005 ◽  
Vol 79 (12) ◽  
pp. 7911-7917 ◽  
Author(s):  
Rainer Gosert ◽  
Wiebke Jendrsczok ◽  
Jan Martin Berke ◽  
Volker Brass ◽  
Hubert E. Blum ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Interactions ◽  
Nonstructural Protein ◽  
Protein Protein Interactions ◽  
Nonstructural Proteins ◽  
Membrane Anchor ◽  
Replication Complex ◽  
Cytosolic Domains

ABSTRACT Protein-protein interactions involved in formation of the membrane-associated hepatitis C virus (HCV) replication complex are poorly understood. Here, we investigated nonstructural proteins with deletions in their membrane anchor domains when expressed in the context of the entire HCV polyprotein. Interactions among cytosolic domains of HCV nonstructural proteins were found not to be sufficiently strong to rescue such mutants to the membrane. Thus, the membrane anchor domains of nonstructural proteins are essential for incorporation of these proteins into the HCV replication complex while interactions among the cytosolic domains appear to be relatively weak. This feature may provide the nonstructural proteins with a certain flexibility to perform their multiple functions during HCV replication.

Predicting protein–protein interactions between human and hepatitis C virus via an ensemble learning method

2014 ◽  
Vol 10 (12) ◽  
pp. 3147-3154 ◽  
Author(s):  
Abbasali Emamjomeh ◽  
Bahram Goliaei ◽  
Javad Zahiri ◽  
Reza Ebrahimpour
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Ensemble Learning ◽  
Protein Interactions ◽  
Learning Method ◽  
Protein Protein Interactions ◽  
Novel Method ◽  
Comprehensive Study

We developed a novel method to predict human–HCV protein–protein interactions, the most comprehensive study of this type.

42 SYSTEMS-LEVEL ANALYSIS OF PROTEIN-PROTEIN INTERACTIONS BETWEEN THE HEPATITIS C VIRUS AND THE CELLULAR INNATE IMMUNITY NETWORK

2011 ◽  
Vol 54 ◽  
pp. S19
Author(s):  
B. de Chassey ◽  
L. Meyniel-Schicklin ◽  
F. Pradezynski ◽  
C. Rabourdin-Combe ◽  
P. André ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Level Analysis
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