丙型肝炎病毒的细胞入侵和相关受体

丙型肝炎病毒(hepatitis C virus,HCV)入侵细胞的过程由多种细胞受体介导,目前已鉴定出人CD81、SR-BI、LDLr、L-SIGN、DC-SIGN、ASGPR、Claudin-1等为HCV的受体.对HCV入侵机制的研究,有助于对HCV入侵的各个环节进行阻断和干预,从而达到预防或/和治疗的目的.近年来,HCVpp及HCVcc模型的建立为HCV入侵细胞的研究提供了重要平台.该文从HCV细胞入侵的研究模型、HCV的细胞受体和HCV入侵细胞的影响因素三方面,综述HCV细胞入侵的研究进展.     

丙型肝炎病毒侵入细胞需CD81和"清道夫"受体SR-B1等共受体

缺乏有效的丙型肝炎病毒(HCV)细胞培养系统是目前研究HCV侵入细胞及其装配机制的主要障碍之一。作者利用其构建的展示HCV包膜糖蛋白E1E2的假型病毒颗粒(HCVpp)对细胞表面CD81和人清道夫受体SR—B1等共受体在HCV侵入细胞中的作用进行了探讨。     

丙型肝炎病毒受体SR-BⅠ的研究进展

丙型肝炎病毒（HCV）是经血液传播而引起急、慢性肝炎的主要致病因子之一,是导致肝硬化、肝细胞癌等终末期肝病的主要原因。位于HCV包膜E2蛋白N端的第1高变区（HVR1）,是介导E2蛋白与B族I型清道夫受体（SR-BⅠ）结合及HCV感染细胞的关键肽段。研究表明,HCV可能利用了SR-BⅠ受体的某些生理功能入侵细胞,进行细胞-细胞间传播。因此,HVR1与SR-BⅠ相互作用的研究除了能深入了解HCV吸附和入侵细胞机制,同时也为治疗和预防HCV感染提供了新的靶点。     

α_1,α_2受体的突触前后定位和亚亚型划分

突触前和突触后都有α_1和α_2受体。对突触前α_1受体的功能有不同看法,可能与突触前α_2受体类似;突触后α_2受体的功能亦与突触后α_1受体类似,但有差别。α_1受体可再划分出高亲和力α_1受体与低亲和力α_1受体:α_(1a)、α_(1b)受体;还有人提出α_(1(?))受体,依赖和不依赖细胞外钙的α_1受体的概念。α_2受体可再划分为低亲和力α_2受体(α_(2L))和高亲和力α_2受体(α_(2H))。     

M1胆碱受体选择性别构激动剂的虚拟筛选和体外活性研究

目的:M1毒蕈碱型乙酰胆碱受体(M1受体)在改善学习和记忆等高级认知功能障碍中起重要作用,本文利用计算机辅助药物设计和高表达各M受体亚型的CHO细胞(Chinese hamster ovary cell,中国仓鼠卵巢细胞),以期筛选获得新型M1受体选择性别构激动剂。方法:通过计算机辅助药物设计方法,对已知具有M1受体选择性作用别构激动剂与M1受体的晶体结构进行对接,确定活性对接口袋,据此进行化合物库虚拟筛选;利用高表达各M受体亚型的CHO细胞,对化合物进行体外活性检测。结果:虚拟筛选得到184个化合物,其中,体外实验显示化合物AJ-292和AG-205-6对M1受体有明显的激动效果,而对M3、M5受体则无影响。结论:综合利用虚拟筛选、结构分析以及特异性活性分析,筛选出具有M1受体高选择性激动作用的化合物AJ-292和AG-205-6,为设计开发新型的M1选择性别构激动剂奠定了基础。     

基底神经节中多巴胺和腺苷受体二聚化及其药理学意义

近年来,大量研究发现G蛋白偶联受体不仅以单体形式,而且以同源或异源二聚体形式存在。腺苷A1受体和多巴胺D1受体以及腺苷A2a受体和多巴胺D2受体分别共存于基底神经节中纹状体向黑质和脚内核投射的神经元以及纹状体向苍白球投射的神经元内。A1／D1、A2a／D2受体形成受体异聚复合体构成了受体一受体之间相互作用的分子基础。腺苷和多巴胺受体之间在细胞水平以及行为水平上拮抗性的相互作用为其在帕金森病、精神分裂症、舞蹈病和药物依赖等疾病的治疗上提供了新的靶向。     

P2z／P2x7嘌呤能受体的研究进展

P2受体是许多种类细胞共有的一类膜受体,能选择性地与胞外ATP(ATPe)结合,产生多种生物效应。P2受体不同于P1受体,因后者也是一类嘌呤能受体,但仅选择性识别腺嘌呤,现称为A1、A2受体。包括ATP在内的多种天然或合成的核苷酸对不同亚型的P2受体有着不同的激活能力,因此根据药理学性质将P2受体分为五类:P2x、P2y、P2u、P2z和P2t,其中前四种是ATP受体,而P2t则是血小板(PLT)表达的ADP受体。P2z受体有一个     

丙型肝炎病毒E蛋白及其受体研究进展

丙型肝炎病毒(HCV)包膜糖蛋白(E蛋白)位于病毒的最外侧,在病毒感染宿主过程中起着重要作用.E蛋白包括E1和E2蛋白,在真核细胞中表达时,其相对分子质量(Mr)大小受糖基化程度的影响,而且两者以某种形式连接形成二聚体,成为HCV包膜的亚单位.HCV E蛋白可能参与了某种信号转导过程.CD81是HCV E蛋白的受体.     

激素在细胞内的作用机理(续)

(二)类固醇激素作用原理 (作用于细胞核的激素) 1.甾体激素的受体细胞对甾体激素的反应依赖于被称作受体(receptor)的蛋白质分子的存在。由激素和受体形成的复合物作用于细胞的基因物质。由内分泌器官所分泌的激素可以影响远距离的无明显关系的组织的细胞,在这些起调节     

丙肝病毒进入的潜在受体及其生物学作用

已确定是假定丙肝病毒（HCV）受体的细胞分子有：CD81蛋白跨膜蛋白、清道夫受体B类Ⅰ型（SR—BI）、甘露糖结合凝集素DC—SIGN和L—SIGN、低密度脂蛋白受体、乙酰肝素蛋白多糖和唾液酸受体。由于在细胞培养基中复制丙肝病毒的困难,因此这些分子大部分是通过分析它们与HCV糖蛋白E2可溶缩短形式之间的相互作用被确定的。近来研究HCV进入的主要步骤是发展假颗粒（HCVpp）,即：把未经修饰的HCV包膜糖蛋白组装到逆转录病毒核心颗粒上。这一方法可对候选受体在HCV复制周期早期步骤中的作用进行研究,所获得的数据现在能够借助新近发展的允许HCV有效扩增的细胞培养系统（HCVcc）被确认。     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Enterovirus 71 3C proteolytically processes the histone H3 N-terminal tail during infection

Highlights
1. The N-terminal tail of histone H3 is specifically cleaved during EV71 infection.
2. Viral protease 3C is identified as a protease responsible for proteolytically processing the N-terminal H3 tail.
3. Our finding reveals a new epigenetic regulatory mechanism for Enterovirus 71 in virus-host interactions.     

Detection of EBV and HHV6 in the Brain Tissue of Patients with Rasmussen’s Encephalitis

Rasmussen’s encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and 16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis, intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8⁺ T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8⁺ T cells are involved in the pathogenesis of RE.     

Perinatal Vertical Transmission of Chikungunya Virus in Ruili,a Town on the Border between China and Myanmar

正Dear Editor,Chikungunya virus (CHIKV), an arbovirus in the family of Togaviridae, genus Alphavirus, is transmitted by the A.aegyptii or A. albopictus mosquito, and causes disease in humans characterized by fever, rash, and arthralgia (Silva and Dermody 2017; Suhrbier 2019). It was first reported in 1953 in Tanzania, and caused only a few outbreaks and sporadic cases in Africa and Asia in last century. However, in the epidemic in 2004, CHIKV acquired mutations that conferred enhanced transmission by the A. albopictus mosquito(Schuffenecker et al. 2006). Since then, it has successively caused outbreaks in Africa, the Indian Ocean, South East Asia, the South America, and Europe (Zeller et al. 2016).     

Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2

In conclusion, the novel visual RT-LAMP assay is a simple, rapid, and sensitive approach for detection of SARS-CoV-2, and it is ready for application in primary care and community hospitals or health care centers, and even patients' own houses in response to the current SARS-CoV-2 epidemic because the assay does not require sophisticated equipment and skilled personnel. Furthermore, it is also ready to be used in fields for screening samples from wild animals and environments to facilitate the identification of potential intermediate hosts that mediate the cross-species transmission of SARS-CoV-2 from bats to humans.