Ait-Goughoulte Malika, Hourioux Christophe, Patient Romuald, Trassard Sylvie, Brand Denys, Roingeard Philippe
INSERM ESPRI 3856, IFR 136, Université François Rabelais, Faculté de Médecine & CHU, 10 boulevard Tonnellé, 37032 Tours, France.
J Gen Virol. 2006 Apr;87(Pt 4):855-860. doi: 10.1099/vir.0.81664-0.
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.
丙型肝炎病毒（HCV）核心蛋白与辛德毕斯病毒复制子一起表达时，在内质网（ER）膜处自组装成丙型肝炎病毒样颗粒（HCV-LP），这为通过电子显微镜研究HCV组装和形态发生提供了机会。该模型用于研究信号肽肽酶（SPP）对HCV核心蛋白的加工是否是HCV-LP组装所必需的。由于关于SPP对突变蛋白的切割存在相互矛盾的报道，因此设计了几个突变体。唯一逃脱SPP加工的核心突变蛋白的产生导致形成多层电子致密的ER膜，没有HCV-LP组装的证据。这些数据揭示了参与SPP切割的HCV核心残基，并表明这种切割对于HCV组装至关重要。
