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Basic Characteristics of Mutations
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Mutation Site
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F172C |
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Mutation Site Sentence
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In particular, the combination of residues previously shown to increase HCV titers in HCVcc propagation system (represented by our S145G/A147V/V151L and F172C/P173S mutants), or the L91C mutation which is specific of the C10M in comparison to the J6 core sequence, were not able to restore the HCV LPs formation when inserted in the JFH-1 core sequence. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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C |
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Standardized Encoding Gene
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Core
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Genotype/Subtype
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- |
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Viral Reference
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AF529293
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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26339783
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Title
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The Replacement of 10 Non-Conserved Residues in the Core Protein of JFH-1 Hepatitis C Virus Improves Its Assembly and Secretion
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Author
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Etienne L,Blanchard E,Boyer A,Desvignes V,Gaillard J,Meunier JC,Roingeard P,Hourioux C
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Journal
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PloS one
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Journal Info
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2015 Sep 4;10(9):e0137182
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Abstract
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Hepatitis C virus (HCV) assembly is still poorly understood. It is thought that trafficking of the HCV core protein to the lipid droplet (LD) surface is essential for its multimerization and association with newly synthesized HCV RNA to form the viral nucleocapsid. We carried out a mapping analysis of several complete HCV genomes of all genotypes, and found that the genotype 2 JFH-1 core protein contained 10 residues different from those of other genotypes. The replacement of these 10 residues of the JFH-1 strain sequence with the most conserved residues deduced from sequence alignments greatly increased virus production. Confocal microscopy of the modified JFH-1 strain in cell culture showed that the mutated JFH-1 core protein, C10M, was present mostly at the endoplasmic reticulum (ER) membrane, but not at the surface of the LDs, even though its trafficking to these organelles was possible. The non-structural 5A protein of HCV was also redirected to ER membranes and colocalized with the C10M core protein. Using a Semliki forest virus vector to overproduce core protein, we demonstrated that the C10M core protein was able to form HCV-like particles, unlike the native JFH-1 core protein. Thus, the substitution of a few selected residues in the JFH-1 core protein modified the subcellular distribution and assembly properties of the protein. These findings suggest that the early steps of HCV assembly occur at the ER membrane rather than at the LD surface. The C10M-JFH-1 strain will be a valuable tool for further studies of HCV morphogenesis.
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Sequence Data
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-
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