Core protein cleavage by signal peptide peptidase is required for hepatitis C virus-like particle assembly.
Hepatitis C virus (HCV) core protein, expressed with a Semliki Forest virus replicon, self-assembles into HCV-like particles (HCV-LP) at the endoplasmic reticulum (ER) membrane, providing an opportunity to study HCV assembly and morphogenesis by electron microscopy. This model was used to investigate whether the processing of the HCV core protein by the signal peptide peptidase (SPP) is required for the HCV-LP assembly. Several mutants were designed as there are conflicting reports concerning the cleavage of mutant proteins by SPP. Production of the only core mutant protein that escaped SPP processing led to the formation of multiple layers of electron-dense ER membrane, with no evidence of HCV-LP assembly. These data shed light on the HCV core residues involved in SPP cleavage and suggest that this cleavage is essential for HCV assembly.
Ait-Goughoulte
Malika
M
INSERM ESPRI 3856, IFR 136, Université François Rabelais, Faculté de Médecine & CHU, 10 boulevard Tonnellé, 37032 Tours, France.
Hourioux
Christophe
C
INSERM ESPRI 3856, IFR 136, Université François Rabelais, Faculté de Médecine & CHU, 10 boulevard Tonnellé, 37032 Tours, France.
Patient
Romuald
R
INSERM ESPRI 3856, IFR 136, Université François Rabelais, Faculté de Médecine & CHU, 10 boulevard Tonnellé, 37032 Tours, France.
Trassard
Sylvie
S
INSERM ESPRI 3856, IFR 136, Université François Rabelais, Faculté de Médecine & CHU, 10 boulevard Tonnellé, 37032 Tours, France.
Brand
Denys
D
INSERM ESPRI 3856, IFR 136, Université François Rabelais, Faculté de Médecine & CHU, 10 boulevard Tonnellé, 37032 Tours, France.
Roingeard
Philippe
P
INSERM ESPRI 3856, IFR 136, Université François Rabelais, Faculté de Médecine & CHU, 10 boulevard Tonnellé, 37032 Tours, France.
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D009154:Mutation; D014162:Transfection; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism*; D019065:Virus Assembly
D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D016282:Aspartic Acid Endopeptidases; C460085:signal peptide peptidase