Neddermann P, Tomei L, Steinkühler C, Gallinari P, Tramontano A, De Francesco R
I.R.B.M-Istituto di Ricerche di Biologia Molecolare P. Angeletti-Pomezia, Rome, Italy.
Biol Chem. 1997 Jun;378(6):469-76.
The hepatitis C virus is the major causative agent of nonA-nonB hepatitis worldwide. Although this virus cannot be cultivated in cell culture, several of its features have been elucidated in the past few years. The viral genome is a single-stranded, 9.5kb long RNA molecule of positive polarity. The viral genome is translated into a single polyprotein of about 3000 amino acids. The virally encoded polyprotein undergoes proteolytic processing by a combination of cellular and viral proteolytic enzymes in order to yield all the mature viral gene products. The gene order of HCV has been determined to be C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B. The mature structural proteins, C, E1 and E2 have been shown to arise from the viral polyprotein via proteolytic processing by host signal peptidases. Conversely, generation of the mature nonstructural proteins relies on the activity of viral proteases. Thus, cleavage at the NS2/NS3 junction is accomplished by a metal-dependent autoprotease encoded within NS2 and the N-terminus of NS3. The remaining cleavages downstream from this site are effected by a serine protease contained within the N-terminal region of NS3. Besides the protease domain, NS3 also contains an RNA helicase domain at its C-terminus. NS3 forms a heterodimeric complex with NS4A. The latter is a membrane protein that has been shown to act as a cofactor of the protease. Whereas the NS5B protein has been shown to be the viral RNA-dependent RNA polymerase, no function has yet been attributed to NS4B and NS5A. The latter is a cytoplasmic phosphoprotein and appears to be involved in mediating the resistance of the hepatitis C virus to the action of interferon.
丙型肝炎病毒是全球范围内非甲非乙型肝炎的主要致病原。尽管该病毒无法在细胞培养中增殖，但在过去几年里已阐明了其一些特性。病毒基因组是一个单链、9.5kb长的正极性RNA分子。病毒基因组被翻译成一个约3000个氨基酸的单一多聚蛋白。病毒编码的多聚蛋白通过细胞和病毒蛋白酶的共同作用进行蛋白水解加工，以产生所有成熟的病毒基因产物。丙型肝炎病毒的基因顺序已确定为C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B。已证明成熟的结构蛋白C、E1和E2是通过宿主信号肽酶对病毒多聚蛋白进行蛋白水解加工而产生的。相反，成熟非结构蛋白的产生依赖于病毒蛋白酶的活性。因此，NS2/NS3连接处的切割是由NS2内编码的金属依赖性自蛋白酶和NS3的N端完成的。该位点下游的其余切割由NS3 N端区域内的丝氨酸蛋白酶完成。除蛋白酶结构域外，NS3在其C端还含有一个RNA解旋酶结构域。NS3与NS4A形成异二聚体复合物。后者是一种膜蛋白，已被证明可作为蛋白酶的辅因子。虽然NS5B蛋白已被证明是病毒RNA依赖性RNA聚合酶，但NS4B和NS5A尚未被赋予任何功能。后者是一种细胞质磷蛋白，似乎参与介导丙型肝炎病毒对干扰素作用的抗性。
