Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions.
Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions.
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DOI：
10.1371/journal.ppat.0030103
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发表时间：
2007-07
期刊：
影响因子：
6.7
通讯作者：
Pietschmann T
中科院分区：
文献类型：
--
作者：
Steinmann E;Penin F;Kallis S;Patel AH;Bartenschlager R;Pietschmann T
丙型肝炎病毒感染与慢性肝病有关，目前影响约3%的世界人口。虽然对单个病毒蛋白的功能已经了解很多，但丙型肝炎病毒p7蛋白在病毒复制中的作用尚不清楚。然而，最近的数据表明，它形成的离子通道可能是抗病毒化合物的靶点。此外，这种蛋白被证明对黑猩猩的传染性是必不可少的。采用新的丙型肝炎病毒感染系统，并利用遗传学方法研究p7在病毒复制周期中的功能，我们发现该蛋白对于跨不同病毒株的感染性病毒粒子的有效组装和释放是必不可少的。我们发现，p7以一种特定于基因的方式促进病毒颗粒的产生，很可能是由于与其他病毒因子的相互作用。另一方面，病毒的进入在很大程度上独立于p7，因为释放的p7缺陷病毒粒子的特异性感染性不受影响。总之，这些观察表明，p7主要参与了丙型肝炎病毒复制周期的后期。最后，我们注意到来自不同分离物的p7变体在促进病毒产生的能力上有很大的差异，这表明p7是一个重要的毒力因子，可能调节适合性，进而调节病毒的持久性和致病。丙型肝炎病毒(丙型肝炎病毒)是一种与严重肝病有关的主要人类病原体，它编码一种名为p7的小膜蛋白。虽然最近的报道表明p7形成跨膜传导离子的通道，并且对丙型肝炎病毒感染是必不可少的，但它在病毒生命周期中的确切作用仍然不清楚。在这项研究中，我们阐明了丙型肝炎病毒依靠p7功能从肝细胞中有效地组装和释放感染性子代病毒粒子。相反，丙型肝炎病毒颗粒进入新的宿主细胞不依赖p7。这一新证据支持了最近提出的将p7纳入病毒孔蛋白家族的提议，该家族包含来自不同病毒的蛋白质，例如HIV-1和A型流感病毒。这组功能相关蛋白的成员形成膜孔，促进病毒释放，在某些情况下也促进病毒进入。此外，我们确定了几个保守的p7残基，这些残基对该蛋白的功能至关重要。这些氨基酸可能稳定p7的结构或直接参与离子的通道。有趣的是，来自不同患者分离株的p7变体在促进病毒产生的能力方面存在差异，这表明p7调节病毒的适合性。总之，这些观察结果为丙型肝炎病毒复制策略的基本方面提供了新的线索。
Hepatitis C virus (HCV) infection is associated with chronic liver disease and currently affects about 3% of the world population. Although much has been learned about the function of individual viral proteins, the role of the HCV p7 protein in virus replication is not known. Recent data, however, suggest that it forms ion channels that may be targeted by antiviral compounds. Moreover, this protein was shown to be essential for infectivity in chimpanzee. Employing the novel HCV infection system and using a genetic approach to investigate the function of p7 in the viral replication cycle, we find that this protein is essential for efficient assembly and release of infectious virions across divergent virus strains. We show that p7 promotes virus particle production in a genotype-specific manner most likely due to interactions with other viral factors. Virus entry, on the other hand, is largely independent of p7, as the specific infectivity of released virions with a defect in p7 was not affected. Together, these observations indicate that p7 is primarily involved in the late phase of the HCV replication cycle. Finally, we note that p7 variants from different isolates deviate substantially in their capacity to promote virus production, suggesting that p7 is an important virulence factor that may modulate fitness and in turn virus persistence and pathogenesis. The hepatitis C virus (HCV), a major human pathogen associated with severe liver disease, encodes a small membrane protein designated p7. Although recent reports indicated that p7 forms channels conducting ions across membranes and is essential for HCV infection, its exact role in the viral life cycle remained elusive. In this study, we illustrate that HCV relies on p7 function for efficient assembly and release of infectious progeny virions from liver cells. Conversely, entry of HCV particles into new host cells is independent of p7. This new evidence supports the recent proposal to include p7 into the family of viroporins that comprises proteins from diverse viruses, for instance, HIV-1 and influenza A virus. Members of this group of functionally related proteins form membrane pores that promote virus release and in some cases also virus entry. Moreover, we identify several conserved p7 residues crucial for functioning of this protein. These amino acids possibly stabilize the structure of p7 or directly participate in channelling of ions. Interestingly, p7 variants from divergent patient isolates differ with regard to their ability to promote virus production, suggesting that p7 modulates viral fitness. Together these observations shed new light on fundamental aspects of the HCV replication strategy.
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影响因子：
4.8
作者：
Bartosch, B;Vitelli, A;Cosset, FL
通讯作者：
Cosset, FL
EUHCVDB：欧洲丙型肝炎病毒数据库。
影响因子：
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影响因子：
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