GB Virus B and Hepatitis C Virus, Distantly Related Hepaciviruses, Share an Entry Factor, Claudin-1.
GB Virus B and Hepatitis C Virus, Distantly Related Hepaciviruses, Share an Entry Factor, Claudin-1.
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DOI：
10.1128/jvi.00469-23
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发表时间：
2023-07-27
影响因子：
5.4
通讯作者：
Mattiuzzo, Giada
中科院分区：
文献类型：
--
作者：
Toon, Kamilla;Kalemera, Mphatso D.;Palor, Machaela;Rose, Nicola J.;Takeuchi, Yasuhiro;Grove, Joe;Mattiuzzo, Giada
由于筛选工作的增加和扩大，过去十年中被归类为肝炎病毒属的病毒种类数量迅速扩大。肝病毒的保守遗传特征表明，它们已经经历了特定的适应，并已进化到劫持类似的宿主蛋白质，以便在肝脏中有效繁殖。在这里，我们开发了假型病毒来阐明GB病毒B（GBV-B B）的进入因子，GB病毒是继丙型肝炎病毒（HCV）之后在动物中描述的第一种肝炎病毒。GBV-B-假型病毒颗粒（GBVBpp）被证明是唯一敏感的感染GBV-B的绢毛猴的血清，验证其作为替代GBV-B进入研究的有用性。我们筛选了人肝癌细胞系的GBVBpp感染，所述人肝癌细胞系被CRISPR/Cas9工程化以消除个体HCV受体/进入因子的表达，并发现封闭蛋白-1对于GBV-B感染是必需的，表明GBV-B和HCV共享进入因子。我们的数据表明，claudin-1通过不同的机制促进HCV和GBV-B进入，因为前者需要第一个细胞外环，后者依赖于包含第二个细胞外环的C-末端区域。claudin-1是这两种肝炎病毒之间共享的进入因子的观察结果表明，紧密连接蛋白在细胞进入过程中具有基本的机械重要性。丙型肝炎病毒（HCV）是一种主要的公共卫生负担;约有5800万人患有慢性HCV感染，并有发生肝硬化和肝癌的风险。为了实现世界卫生组织到2030年消除肝炎的目标，需要新的治疗方法和疫苗。了解HCV如何进入细胞可以为针对感染第一阶段的新疫苗和治疗方法的设计提供信息。然而，HCV进入细胞的机制是复杂的，并且很少被描述。研究进入相关的肝炎病毒将增加知识的分子机制的第一阶段的HCV感染，如膜融合，并告知结构指导的HCV疫苗设计;在这项工作中，我们已经确定了一种蛋白质，claudin-1，有利于进入HCV相关的肝炎病毒，但没有描述的机制为HCV。对其他肝炎病毒的类似研究可能揭示进入因子的共性，并可能揭示新的机制。
Due to increased and broadened screening efforts, the last decade has seen a rapid expansion in the number of viral species classified into the Hepacivirus genus. Conserved genetic features of hepaciviruses suggest that they have undergone specific adaptation and have evolved to hijack similar host proteins for efficient propagation in the liver. Here, we developed pseudotyped viruses to elucidate the entry factors of GB virus B (GBV-B), the first hepacivirus described in an animal after hepatitis C virus (HCV). GBV-B-pseudotyped viral particles (GBVBpp) were shown to be uniquely sensitive to the sera of tamarins infected with GBV-B, validating their usefulness as a surrogate for GBV-B entry studies. We screened GBVBpp infection of human hepatoma cell lines that were CRISPR/Cas9 engineered to ablate the expression of individual HCV receptors/entry factors and found that claudin-1 is essential for GBV-B infection, indicating the GBV-B and HCV share an entry factor. Our data suggest that claudin-1 facilitates HCV and GBV-B entry through distinct mechanisms since the former requires the first extracellular loop and the latter is reliant on a C-terminal region containing the second extracellular loop. The observation that claudin-1 is an entry factor shared between these two hepaciviruses suggests that the tight junction protein is of fundamental mechanistic importance during cell entry. IMPORTANCE Hepatitis C virus (HCV) is a major public health burden; approximately 58 million individuals have chronic HCV infection and are at risk of developing cirrhosis and liver cancer. To achieve the World Health Organization’s target of eliminating hepatitis by 2030, new therapeutics and vaccines are needed. Understanding how HCV enters cells can inform the design of new vaccines and treatments targeting the first stage of infection. However, the HCV cell entry mechanism is complex and has been sparsely described. Studying the entry of related hepaciviruses will increase the knowledge of the molecular mechanisms of the first stages of HCV infection, such as membrane fusion, and inform structure-guided HCV vaccine design; in this work, we have identified a protein, claudin-1, that facilitates the entry of an HCV-related hepacivirus but with a mechanism not described for HCV. Similar work on other hepaciviruses may unveil a commonality of entry factors and, possibly, new mechanisms.
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影响因子：
3.7
作者：
Bukh, J;Apgar, CL;Yanagi, M
通讯作者：
Yanagi, M
影响因子：
12.7
作者：
Bukh, J;Apgar, CL;Purcell, RH
通讯作者：
Purcell, RH
DOI：
10.1083/jcb.141.7.1539
发表时间：
1998-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Furuse M;Fujita K;Hiiragi T;Fujimoto K;Tsukita S
通讯作者：
Tsukita S
DOI：
10.1073/pnas.2335981100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Bartosch, B;Bukh, J;Purcell, RH
通讯作者：
Purcell, RH
影响因子：
14.8
作者：
Heckman, Karin L.;Pease, Larry R.
通讯作者：
Pease, Larry R.