The Replacement of 10 Non-Conserved Residues in the Core Protein of JFH-1 Hepatitis C Virus Improves Its Assembly and Secretion

PloS One
Loïc EtienneChristophe Hourioux

Abstract

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 r...Continue Reading

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Citations

Feb 25, 2017·Virus Genes·Viviana FalcónJuan Kourı
Mar 4, 2020·Cold Spring Harbor Perspectives in Medicine·Kunitada Shimotohno
Jan 4, 2017··Afiono Agung Prasetyo, Afiono Agung Prasetyo

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Methods Mentioned

BETA
PCR
electrophoresis
transfections
transfection
electron microscopy
confocal microscopy
transfect

Software Mentioned

Filemaker
Imaris
Bioedit
Clustalw

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