title: Signal peptide peptidase promotes the formation of hepatitis C virus non-enveloped particles and is captured on the viral membrane during assembly.
abstract: The maturation of the core protein (C) of Hepatitis C virus (HCV) is controlled by the signal peptidase (sp) and signal peptide peptidase (spp) of the host. To date, it remains unknown whether spp cleavage influences viral infectivity and/or the assembly process. Here, evidence is provided that cleavage by spp is not required for assembly of nucleocapsid-like particles (NLPs) in yeast (Pichia pastoris). The immature NLPs (not processed by spp) show a density of 1.11 g ml(-1) on sucrose gradients and a diameter of 50 nm. Co-expression of human spp (hspp) with C generates the 21 kDa mature form of the protein and promotes the accumulation of non-enveloped particles. The amount of non-enveloped particles accumulating in the cell was correlated directly with the expression level of hspp. Furthermore, immunocapture studies showed that hspp was embedded in the membranes of enveloped particles. These results suggest that maturation of the C protein can occur after formation of the enveloped particles and that the abundance of hspp influences the types of particle accumulating in the cells.
authors.affiliation: Infectious Disease Research Centre, Pav. CHUL, University of Laval, 2705 boulevard Laurier, Québec (Québec), Canada G1V 4G2.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Majeau
authors.affiliation: Infectious Disease Research Centre, Pav. CHUL, University of Laval, 2705 boulevard Laurier, Québec (Québec), Canada G1V 4G2.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gagné
authors.affiliation: Infectious Disease Research Centre, Pav. CHUL, University of Laval, 2705 boulevard Laurier, Québec (Québec), Canada G1V 4G2.
authors.forename: Marilène
authors.initials: M
authors.lastname: Bolduc
authors.affiliation: Infectious Disease Research Centre, Pav. CHUL, University of Laval, 2705 boulevard Laurier, Québec (Québec), Canada G1V 4G2.
authors.forename: Denis
authors.initials: D
authors.lastname: Leclerc
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000502:physiology*; D016174:Hepacivirus / Q000502:physiology* / Q000648:ultrastructure; D010843:Pichia / Q000821:virology*; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics; D019065:Virus Assembly / Q000502:physiology*
chemical_list: D014758:Viral Core Proteins; D016282:Aspartic Acid Endopeptidases; C460085:signal peptide peptidase