麻疹病毒受体与病毒侵入

麻疹病毒是一种具囊膜的负链RNA病毒,两种主要的囊膜蛋白血凝素蛋白(H)和膜融合蛋白(F)表达在膜表面负责病毒侵入过程中与宿主受体的结合和膜融合过程.病毒囊膜蛋白与受体的相互作用是病毒侵入宿主的关键步骤,决定了病毒感染能力、种属和组织嗜性.因此,囊膜病毒与受体的结合位点往往成为重要的抗病毒药物的靶点.目前已发现的3种麻疹病毒受体包括CD46、SLAM和Nectin-4.以下综述了麻疹病毒受体的特征及在病毒侵入中的作用、麻疹病毒H蛋白与受体的相互作用机制,为抗病毒药物设计及麻疹病毒作为肿瘤治疗性载体的应用提供理论依据.     

疱疹病毒膜融合的分子机制

囊膜病毒与宿主细胞的膜融合是病毒入侵宿主细胞的重要过程,这一过程涉及到病毒囊膜表面糖蛋白与宿主细胞表面受体之间的相互作用和构象变化．疱疹病毒有多个糖蛋白及不同类型的细胞作用受体,相应的受体-糖蛋白复合体构成方式也有多种,其引致的膜融合机制被认为是目前病毒融合机制研究中最复杂的,近年来被广泛研究并取得突破性进展．从病毒糖蛋白与相应受体的结构与功能、受体-糖蛋白复合体的形成与入侵途径,以及膜融合模式几个方面,全面综述疱疹病毒膜融合的分子机制,并展望了未来研究趋势．     

囊膜病毒膜融合分子机制研究进展

囊膜病毒通过病毒与宿主细胞膜融合的方式感染宿主,病毒囊膜蛋白介导了膜融合过程。根据这些囊膜蛋白在病毒囊膜表面的排列、蛋白结构及其在融合肽中的位置不同,可将囊膜病毒分为三类,其利用这些囊膜特殊的蛋白分子与受体相互作用完成膜融合。在分子水平上研究这一过程有助于认识病毒侵染的本质和发现关键环节,达到预防与治疗病毒病的目的。     

SARS-CoV-2入侵细胞的研究进展

新型冠状病毒(SARS-CoV-2)感染引发的肺炎疫情已蔓延全球,尽快认清病毒感染规律和致病机制是做好疫情防控的基础。SARS-CoV-2表面的刺突蛋白(Spike,S)识别靶细胞受体并与之结合,诱导病毒与细胞的膜融合,是病毒侵入宿主细胞的第一步,也是预防和治疗病毒感染的关键靶点。大量研究揭示了病毒进入细胞的分子机制,本文将主要对SARS-CoV-2入侵细胞的研究成果进行总结,并简要叙述以该环节为靶点的药物和疫苗研发现状。     

冠状病毒感染细胞的受体结合机制

病毒感染宿主细胞是病毒致病的关键所在,病毒感染细胞需要与其受体相结合,介导其与细胞的膜融合反应。本综述了冠状病毒受体结合机制的研究进展,以及其在SARS病毒致病机制中可能的作用。     

病毒受体的研究方法

1概况病毒受体可以定义为位于宿主细胞表面能够被病毒吸附蛋白识别并与之结合,从而引起病毒感染的分子复合物,其化学本质是糖蛋白、蛋白聚糖、脂类或糖脂,大多数属于蛋白质。病毒受体可以是单体也可以是多分子复合物,具有特异性、高亲和性、饱和性、结合位点及靶细胞部位的有限性以及独特的生物学活性等[1]。病毒受体是公认的引发病毒感染宿主细胞的主要决定因素,也是影响病毒宿主特异性和组织亲嗜性的决定因素之一。研究病毒受体的特性及其功能对于从分子水平阐明病毒感染与免疫的机制,深刻理解病毒与宿主细胞的相互关系,研制更有效的病毒…     

整联蛋白与口蹄疫病毒感染

整联蛋白是一类重要的细胞表面分子,除介导细胞与胞外基质及细胞间的粘附外,还对细胞的识别、生长和分化具有重要作用。FMDV对细胞的侵染依赖于宿主细胞受体,整联蛋白作为口蹄疫病毒侵入细胞的关键决定簇,在致病机制、组织和器官嗜性中具有重要作用。本文就整联蛋白的结构、功能及在FMDV感染中的作用等方面进行了综述,以期阐明FMDV侵染细胞的机制。     

基于CRISPR/Cas9技术的高通量筛选平台:发掘病毒复制相关宿主分子的新途径

病毒作为严格的细胞内寄生生物,需要多种宿主蛋白辅助其完成生命周期。寻找与病毒复制相关的宿主因子并揭示其作用机制,将有助于阐明病毒的感染机制,为疫病的防治提供新靶标。与RNA干扰技术相比,近年来兴起的CRISPR/Cas9技术能更特异、高效、准确地实现基因组编辑,因而在功能基因研究中得到更广泛应用。而基于CRISPR/Cas9系统的宿主全基因组sgRNA文库高通量筛选技术平台,可快速发现参与病毒侵入、复制等生物学过程的关键宿主因子,通过明确病毒-宿主分子相互作用进而揭示病毒的生命周期,为分子病毒学和免疫学提供了强大的研究工具。本文主要总结了基于CRISPR/Cas9技术的高通量筛选平台的具体筛选流程,归纳和讨论了该平台在筛选调控病毒复制相关宿主因子中的应用现状和发展前景。     

轮状病毒受体的研究进展

本文从病毒的宿主、受全唾液酸残基及受体分子的化学特征等几个方面介绍了目前对轮状病毒受体分子的研究水平,对病毒受体的研究,有助于了解病毒及受体相互作用的分子机制,防治有重要意义。     

登革热2型病毒感染人内皮细胞的机制

登革热病毒(DEN)通过两种机制感染宿主细胞,即与病毒IgG形成复合物结合于Fc受体,或是病毒糖蛋白直接与宿主细胞特异性受体结合。第一种机制已做研究,发现登革热出血/休克综合征的病毒滴度的增高与这种IgG-Fc介导的抗体增高有关,而对第二种机制的研究较少,且一直未发现DEN的宿主细胞受体。     

综述: 病毒与宿主细胞的糖基化修饰及相关功能

病毒的复制和对宿主的入侵与自身结构蛋白的糖基化修饰密切相关．对于宿主而言,在病毒感染宿主和宿主抗病毒的过程中,宿主的糖基化过程一方面可抑制病毒的复制和入侵,另一方面可促进病毒对宿主的感染,抑制宿主糖苷酶可抑制病毒的复制．从病毒方面来看,由于病毒自身缺乏糖基化修饰系统,病毒的糖基化过程是借宿主细胞内的合成系统对自身进行糖基化修饰．病毒的糖基化过程对病毒蛋白的折叠与稳定、病毒的感染和入侵、参与识别宿主细胞受体和参与病毒的免疫逃逸等过程起着重要的作用．随着糖基化研究技术的发展,以糖基化为基础的功能应用也越来越深入：如新型病毒疫苗和新型抗病毒药物的研制,以糖蛋白质组学研究为基础的质谱技术和生物信息学方法的发展,以及利用糖基化对病毒性疾病的诊断和治疗等,这些均为糖基化深入研究发展奠定了基础．本文就病毒与宿主细胞糖基化过程、相关功能以及研究应用等进展作一综述．     

Human immunodeficiency virus type 1 replication in dendritic cell-T-cell cocultures is increased upon incorporation of host LFA-1 due to higher levels of virus production in immature dendritic cells

Dendritic cells (DCs) act as a portal for invasion by human immunodeficiency virus type-1 (HIV-1). Here, we investigated whether virion-incorporated host cell membrane proteins can affect virus replication in DC-T-cell cocultures. Using isogenic viruses either devoid of or bearing host-derived leukocyte function-associated antigen 1 (LFA-1), we showed that HIV-1 production is augmented when LFA-1-bearing virions are used compared to that for viral entities lacking this adhesion molecule. This phenomenon was observed in immature monocyte-derived DCs (IM-MDDCs) only and not in DCs displaying a mature phenotype. The increase is not due to higher virus production in responder CD4(+) T cells but rather is linked with a more important productive infection of IM-MDDCs. We provided evidence that virus-associated host LFA-1 molecules do not affect a late event in the HIV-1 life cycle but rather exert an effect on an early step in virus replication. We demonstrated that the enhancement of productive infection of IM-MDDCs that is conferred by virus-anchored host LFA-1 involves the protein kinase A (PKA) and PKC signal transduction pathways. The biological significance of this phenomenon was established by performing experiments with virus stocks produced in primary human cells and anti-LFA-1 antibodies. Together, our results indicate that the association between some virus-bound host proteins and their natural cognate ligands can modulate de novo HIV-1 production by IM-MDDCs. Therefore, the additional interactions between virus-bound host cell membrane constituents and counter receptors on the surfaces of DCs can influence HIV-1 replication in IM-MDDC-T-cell cocultures.     

冠状病毒S蛋白及其受体的结构和功能

冠状病毒是有包膜的单股正链RNA病毒。作为人和动物的重要致病原,冠状病毒感染主要导致宿主呼吸系统、肝脏、胃肠道以及神经系统出现急性或慢性症状。2000年以来,传染性非典型肺炎和中东呼吸综合征的暴发,以及猪流行性腹泻病毒在全球猪群中的暴发流行,引起大家对动物冠状病毒的极大重视。S蛋白具有受体结合活性和膜融合活性,是冠状病毒感染细胞的关键蛋白;S蛋白在病毒的组织或宿主嗜性和毒力等方面发挥重要作用。本文重点对近年来冠状病毒S蛋白的结构、功能以及S蛋白与受体相互作用的研究进行综述,以期为冠状病毒的入侵机制和反向遗传学研究以及受体阻断药物的开发提供参考。     

Listeria monocytogenes cell invasion: a new role for cofilin in co-ordinating actin dynamics and membrane lipids

Actin reorganization, mediated by the actin dynamizing protein cofilin, is essential for host cell invasion by the intracellular pathogenic bacterium Listeria monocytogenes. During invasion, the InlB bacterial surface ligands closely interact with host cell Met receptors to induce phagocytosis. In this issue of Molecular Microbiology, Han et al., 2011 clearly demonstrate that phospholipase D (PLD)-dependent production of membrane phosphatidic acid is required for invasion. They further show that the phosphorylated form of cofilin, which is inactive in actin binding, is necessary for the activation of the PLD1 isoform. Although cofilin-independent PLD2 can also mediate internalization, it is a phospho-cofilin-dependent balanced production of phosphatidic acid that is required for optimal Listeria internalization. Cofilin-dependent membrane lipid remodelling has important implications for cofilin function that go well beyond its direct effects on actin.     

Trypanosoma cruzi: Participation of cholesterol and placental alkaline phosphatase in the host cell invasion

One of the most important parasitic endemic diseases in Latin America is Chagas disease, with almost 20 million people being infected and 60 million others at risk of infection. In the cell infection by Trypanosoma cruzi, the first step is contact with the host cell by receptors and ligands on the membrane. It is known that lipids play an important role in the interaction process between pathogens and host cells with lipid rafts being highly specialized regions of the plasma membrane that are enriched in cholesterol and sphingolipids. We explored whether the treatment with methyl-beta-cyclodextrin alone or by adding Mevinolin, an inhibitor of cholesterol synthesis could deplete membrane cholesterol of the HEp2 cell and if this treatment could affect the trypomastigote infection into the host cell. These treatments led to a leakage of cholesterol, and concomitantly, PLAP enzyme and unidentified proteins resulting in a decrease of the invasion process. However, the GGTP enzyme was not liberated from the host cell membranes.     

动物关键模式识别受体及其抗病毒天然免疫作用研究进展

天然免疫系统是动物抵御病原入侵的第一道防线,在机体抗病毒感染过程中发挥重要作用,模式识别受体（pattern-recognition receptors,PRRs）是天然免疫系统的重要成分,动物机体的抗病毒免疫机制是由一系列PRRs对病原体的识别所启动的。近年来识别和感受病原体的一系列动物PRRs受到广泛关注,成为动物医学领域的研究热点,为揭示动物复杂的抗病毒天然免疫反应提供了新思路。该文简要介绍动物Toll样受体（Toll-like receptors,TLRs）和维甲酸诱导基因Ⅰ样受体（RIG-I like receptors,RLRs）的分子特征及其介导的抗病毒天然免疫作用研究进展。     

Novel strategy in Trypanosoma cruzi cell invasion: implication of cholesterol and host cell microdomains

Trypanosoma cruzi, the etiological agent of Chagas' disease, is an obligatory intracellular parasite in the mammalian host. In order to invade a wide variety of mammalian cells, T. cruzi engages parasite components that are differentially expressed among strains and infective forms. Because the identification of putative protein receptors has been particularly challenging, we investigated whether cholesterol and membrane rafts, sterol- and sphingolipid-enriched membrane domains, could be general host surface components involved in invasion of metacyclic trypomastigotes and extracellular amastigotes of two parasite strains with distinct infectivities. HeLa or Vero cells treated with methyl-beta-cyclodextrin (MbetaCD) are less susceptible to invasion by both infective forms, and the effect was dose-dependent for trypomastigote but not amastigote invasion. Moreover, treatment of parasites with MbetaCD only inhibited trypomastigote invasion. Filipin labeling confirmed that host cell cholesterol concentrated at the invasion sites. Binding of a cholera toxin B subunit (CTX-B) to ganglioside GM1, a marker of membrane rafts, inhibited parasite infection. Cell labeling with CTX-B conjugated to fluorescein isothiocyanate revealed that not only cholesterol but also GM1 is implicated in parasite entry. These findings thus indicate that microdomains present in mammalian cell membranes, that are enriched in cholesterol and GM1, are involved in invasion by T. cruzi infective forms.     

Novel Insights into Cell Entry of Emerging Human Pathogenic Arenaviruses

Viral hemorrhagic fevers caused by emerging RNA viruses of the Arenavirus family are among the most devastating human diseases. Climate change, global trade, and increasing urbanization promote the emergence and re-emergence of these human pathogenic viruses. Emerging pathogenic arenaviruses are of zoonotic origin and reservoir-to-human transmission is crucial for spillover into human populations. Host cell attachment and entry are the first and most fundamental steps of every virus infection and represent major barriers for zoonotic transmission. During host cell invasion, viruses critically depend on cellular factors, including receptors, co-receptors, and regulatory proteins of endocytosis. An in-depth understanding of the complex interaction of a virus with cellular factors implicated in host cell entry is therefore crucial to predict the risk of zoonotic transmission, define the tissue tropism, and assess disease potential. Over the past years, investigation of the molecular and cellular mechanisms underlying host cell invasion of human pathogenic arenaviruses uncovered remarkable viral strategies and provided novel insights into viral adaptation and virus–host co-evolution that will be covered in the present review.     

Glycosylation at Asn91 of H1N1 haemagglutinin affects binding to glycan receptors

The glycoprotein HA (haemagglutinin) on the surface of influenza A virus plays a central role in recognition and binding to specific host cell-surface glycan receptors and in fusion of viral membrane to the host nuclear membrane during viral replication. Given the abundance of HA on the viral surface, this protein is also the primary target for host innate and adaptive immune responses. Although addition of glycosylation sites on HA are a part of viral evolution to evade the host immune responses, there are specific glycosylation sites that are conserved during most of the evolution of the virus. In the present study, it was demonstrated that one such conserved glycosylation site at Asn(91) in H1N1 HA critically governs the glycan receptor-binding specificity and hence would potentially impinge on the host adaptation of the virus.