A single point mutation in E2 enhances hepatitis C virus infectivity and alters lipoprotein association of viral particles.
A single point mutation in E2 enhances hepatitis C virus infectivity and alters lipoprotein association of viral particles.
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DOI：
10.1016/j.virol.2009.09.006
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发表时间：
2009-12
期刊：
影响因子：
3.7
通讯作者：
Wanyin Tao;Chun Xu;Q. Ding;Rui Li;Y. Xiang;Josan Chung;Jin Zhong
中科院分区：
文献类型：
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作者：
Wanyin Tao;Chun Xu;Q. Ding;Rui Li;Y. Xiang;Josan Chung;Jin Zhong
丙型肝炎病毒（HCV）感染是一个主要的世界性健康问题。我们以前的研究结果表明，HCV在体外持续感染期间进化以获得增强的感染性和改变的浮力密度分布。在这里，我们发现，在HCV E2的点突变I414T是主要负责这些表型变化。虽然I414 T突变对HCV RNA复制和病毒进入没有显著影响，但它增强了感染性病毒颗粒的产生，并降低了病毒进入对HCV受体水平的依赖性。此外，我们发现，I414 T突变减少了与低密度脂蛋白或极低密度脂蛋白在病毒分泌过程中的病毒颗粒的协会，和脱脂病毒的感染是更敏感的阻断抗E2中和抗体和重组CD81蛋白。我们的研究结果提供了更多的了解脂蛋白协会在HCV生命周期中的作用。
Hepatitis C virus (HCV) infection is a major worldwide health problem. Our previous results showed that HCV evolved to gain the enhanced infectivity and altered buoyant density distribution during persistent infections in vitro. Here we showed that a point mutation I414T in HCV E2 was mainly responsible for these phenotypic changes. While the I414T mutation had no significant effect on HCV RNA replication and viral entry, it enhanced the production of infectious viral particles and decreased the dependency of viral entry on the levels of HCV receptors. Furthermore, we showed that the I414T mutation reduced the association of viral particles with low-density lipoprotein or very low-density lipoproteins during the virus secretion process, and the infection of the delipidated virus was more sensitive to the blockade by an anti-E2 neutralizing antibody and recombinant CD81 proteins. Our results provided more insights into understanding the roles of lipoprotein associations in HCV life cycle.