丙型肝炎病毒
1974年Golafield 首先报告输血后非甲非乙型肝炎。1989年英国科学家迈克尔·侯顿(Michael Houghton)和他的同事们测出了病毒的基因序列,克隆出了丙肝病毒,并命名本病及其病毒为丙型肝炎(HepatitisC)和丙型肝炎病毒(HCV)。由于HCV基因组在结构和表型特征上与人黄病毒和瘟病毒相类似,将其归为黄病毒科HCV。 2017年10月27日,世界卫生组织国际癌症研究机构公布的致癌物清单初步整理参考,丙型肝炎病毒(慢性感染)在一类致癌物清单中。
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In 1974, Golafield first reported post-transfusion non-A, non-B hepatitis. In 1989, British scientist Michael Houghton and his colleagues identified the viral genetic sequence, cloned the Hepatitis C virus (HCV), and named this disease and its virus as Hepatitis C (HepatitisC) and Hepatitis C Virus (HCV) respectively. Due to the structural and phenotypic similarities of HCV's genome with Flavivirus and Pestivirus, it was categorized under the Flaviviridae family as HCV. On October 27, 2017, the World Health Organization's International Agency for Research on Cancer released a preliminary reference list of carcinogens, placing the Hepatitis C Virus (chronic infection) in the Category 1 list of carcinogens.
Biological Characteristics
Morphology and Cultivation The HCV virus is spherical in shape, with a diameter of less than 80nm (36-40nm in liver cells, 36-62nm in blood). It is a single-stranded positive-sense RNA virus enveloped by a lipid bilayer with spikes on it. HCV can only be cultivated in three in-vitro cell systems: Huh7, Huh7.5, and Huh7.5.1. Chimpanzees can be infected with HCV, but the symptoms are mild.
Genetic Structure The HCV-RNA consists of approximately 9500-10000bp. The 5′ and 3′ non-coding regions (NCR) are 319-341 bp and 27-55 bp respectively, containing several direct and inverted repeat sequences, possibly associated with genome replication. A single open reading frame (ORF) follows immediately downstream of the 5′ non-coding region. The genome arrangement is 5'-C-E1-E2-p7-NS2-NS3-NS4-NS5-3', encoding a polyprotein precursor of about 3014 amino acid residues. This precursor is later cleaved into ten viral proteins by both host and viral proteases. These include three structural proteins: the 19kDa nucleocapsid protein (or core protein, Core) and two glycoproteins (33 kDa E1 protein and 72 kDa E2 protein). p7 encodes an intra-membrane protein that might function as an ion channel. Non-structural proteins include NS2, NS3, NS4A, NS5A, and NS5B. NS2 and NS3 have protease activity and are involved in the cleavage of the viral polyprotein precursor. Furthermore, NS3 has helicase activity and plays a role in unwinding HCV-RNA for RNA replication. The function of NS4 is still unclear. NS5A is a phosphoprotein that interacts with various host cell proteins and is crucial for viral replication. NS5B has RNA-dependent RNA polymerase activity, essential for HCV genome replication.
Variability HCV exhibits significant heterogeneity and high variability. Analyses of known complete genomic sequences of HCV strains show considerable differences in nucleotide and amino acid sequences. The variations in different parts of the HCV genome are inconsistent; for instance, the 5′-CR is the most conserved with homology between 92-100%, while the 3′NCR region is highly variable. Among the coding genes of HCV, the C region is the most conserved, followed by the non-structural (NS) region, and the region coding for the envelope protein E2/NS1 has the highest variability and is called the hyper-variable region.
It is a virus that can potentially lead to cancer.
1974年Golafield 首先报告输血后非甲非乙型肝炎。1989年英国科学家迈克尔·侯顿(Michael Houghton)和他的同事们测出了病毒的基因序列,克隆出了丙肝病毒,并命名本病及其病毒为丙型肝炎(HepatitisC)和丙型肝炎病毒(HCV)。由于HCV基因组在结构和表型特征上与人黄病毒和瘟病毒相类似,将其归为黄病毒科HCV。
2017年10月27日,世界卫生组织国际癌症研究机构公布的致癌物清单初步整理参考,丙型肝炎病毒(慢性感染)在一类致癌物清单中。
1. 形态培养
HCV病毒体呈球形,直径小于80nm(在肝细胞中为36~40nm,在血液中为36-62nm ),为单股正链RNA病毒,在核衣壳外包绕含脂质的囊膜,囊膜上有刺突。HCV仅有Huh7, Huh7.5, Huh7.5.1三种体外细胞培养系统,黑猩猩可感染HCV,但症状较轻。
2. 基因结构
HCV-RNA约有9500-10000bp组成,5′和3′非编码区(NCR)分别有319-341 bp,和27-55 bp,含有几个顺向和反向重复序列,可能与基因复制有关。在5′非编码区下游紧接一可读框(ORF),其中基因组排列顺序为5'-C-E1-E2-p7-NS2-NS3-NS4-NS5-3',能编码一由长度约为由3014个氨基酸残基组成的多聚蛋白质前体,后者可经宿主细胞和病毒自身蛋白酶作用后,裂解成10种病毒蛋白,包括三种结构蛋白,即分子量19kDa的核衣壳蛋白(或称核心蛋白,Core)和两种糖蛋白(分子量为33 kDa的E1蛋白,分子量72 kDa的E2蛋白),p7编码一种膜内在蛋白,其功能可能是一种离子通道。非结构蛋白部分则包括NS2,NS3, NS4A,NS5A和NS5B,它对病毒的生活周期非常重要。NS2和NS3具有蛋白酶活性,参与病毒多聚蛋白前体的切割。此外,NS3蛋白还具有螺旋酶活性,参与解旋HCV-RNA分子,以协助RNA复制,NS4的功能尚不清楚。NS5A是一种磷酸蛋白,可以与多种宿主细胞蛋白相互作用,对于病毒的复制起重要作用。而NS5B则具有RNA依赖的RNA聚合酶活性,参与HCV基因组复制。
3. 变异性
HCV具有显著异源性和高度可变性,对已知全部基因组序列的HCV株进行分析比较其核苷酸和氨基酸序列存在较大差异。并表现HCV基因组各部位的变异程度不相一致,如5′-CR最保守,同源性在92-100%,而3′NCR区变异程度较高,在HCV的编码基因中,C区最保守、非结构(NS)区次之,编码囊膜蛋白E2/NS1可变性最高称为高可变区。
它是一种可能导致癌症的病毒。
1974年Golafield 首先报告输血后非甲非乙型肝炎。1989年英国科学家迈克尔·侯顿(Michael Houghton)和他的同事们测出了病毒的基因序列,克隆出了丙肝病毒,并命名本病及其病毒为丙型肝炎(HepatitisC)和丙型肝炎病毒(HCV)。由于HCV基因组在结构和表型特征上与人黄病毒和瘟病毒相类似,将其归为黄病毒科HCV。 2017年10月27日,世界卫生组织国际癌症研究机构公布的致癌物清单初步整理参考,丙型肝炎病毒(慢性感染)在一类致癌物清单中。