FLU VIRUS RNP COMPLEX

流感病毒 RNP 复合物

• 批准号: 7953811
• 负责人: Yizhi Jane Tao
• 金额: $ 0.87万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953811
• 关键词: Africa; Asia; Binding; Binding Sites; Birds; Cell Nucleus; Charge; Complex; Computer Retrieval of Information on Scientific Projects Database; Digestion; Electron Microscopy; Europe; Figs - dietary; Funding; Genome; Genomics; Grant; Human; Influenza; Influenza A virus; Influenza Virus Infected Cells; Institution; Laboratories; Length; Life; Molecular Biology; Mutation; Nucleoproteins; Play; Polymerase; Polymers; Prevention; Process; Proteins; Public Health; RNA; RNA Binding; RNA Viruses; RNA replication; Rabies virus; Research; Research Personnel; Resistance; Resources; Rhabdoviridae; Ribonucleases; Ribonucleoproteins; Role; Source; Structure; Tail; United States National Institutes of Health; Vesicular stomatitis Indiana virus; Viral; Viral Genome; Virus; Virus Diseases; influenza A virus nucleoprotein; influenzavirus; macromolecule; mortality; pandemic disease; parainfluenza virus; trafficking; viral RNA

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Influenza is a major public health concern each year, and influenza A virus can cause widespread pandemics with high mortality rates. Currently, there are grave concerns that the avian H5N1 influenza A virus, which has spread from Asia to Europe and Africa, may gain the ability to be transmitted efficiently between humans, resulting in a worldwide pandemic that could claim a large number of human lives. For better prevention and treatment of human influenza virus infections, it is critical that we obtain a comprehensive understanding of the basic molecular biology of influenza viruses. Influenza viruses are a group of negative-strand (-) RNA viruses that transcribe and replicate their viral RNAs in the cell nucleus. Like other (-)-strand RNA viruses, the segmented genome of influenza A viruses, eight segments in total, is encapsidated in the form of ribonucleoprotein (RNP) complexes. The nucleoprotein (NP), the major protein component of RNPs, binds along the entire length of each genomic RNA segment, forming the double-helical RNP structures found in mature virus. The viral polymerase, consisting of PA, PB1, and PB2 subunits, is bound to the two RNA termini of the RNP. As one of the most abundant proteins made in infected cells, influenza virus NP has essential roles in many important viral processes, including intracellular trafficking of viral genome, viral RNA replication, and the assembly and packaging of viral genome in progeny viruses. The crystal structure of influenza A virus NP has recently been determined in our laboratory [1]. Organized as trimers in the crystal, NP folds into a two-domain structure with a topology completely different from that of the rhabdovirus NP (Fig. 2). A short tail loop, consisting of residues 402 to 428, is likely to play an important role in NP oligomerization, as single-residue mutation in this region causes a total loss of oligomerization. A large positively charged groove was identified at the exterior of the NP trimer at the interface between the two domains. An external RNA binding site indicates that RNA is likely to be exposed in the influenza virus RNPs, different from the situation in non-segmented RNA viruses [2]. This structural difference explains previous results that showed fundamental differences between influenza RNPs and the RNPs of non-segmented (-)-strand RNA viruses like VSV and rabies virus. For example, the viral RNA in influenza virus RNPs is digested by RNase treatment, whereas the viral RNA in the RNPs of parainfluenza viruses and rhabdoviruses is completely resistant to RNase digestion [3-5]. In addition, polyvinylsufate (PVS), a negatively charged polymer, is able to completely displace RNA from influenza virus RNP, whereas it has no effect on RNPs from VSV [6].

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 每年流感是一个主要的公共卫生问题，流感病毒可能会引起广泛的大流行病，死亡率很高。 当前，人们对从亚洲传播到欧洲和非洲的鸟类H5N1流感病毒可能会获得严重的担忧，可能会获得在人类之间有效传播的能力，从而导致全球大流行，该大流行可能夺走大量人类的生命。为了更好地预防和治疗人类流感病毒感染，至关重要的是，我们必须全面了解流感病毒的基本分子生物学。流感病毒是一组负链（ - ）RNA病毒，可转录和复制其病毒RNA在细胞核中。与其他（ - ） - 链RNA病毒一样，流感病毒的分段基因组，总共八个片段，以核糖核蛋白（RNP）复合物的形式封装。 RNP的主要蛋白质成分（NP）沿每个基因组RNA段的整个长度结合，形成了在成熟病毒中发现的双螺旋RNP结构。由PA，PB1和PB2亚基组成的病毒聚合酶与RNP的两个RNA末端结合。 作为感染细胞中最丰富的蛋白质之一，流感病毒NP在许多重要的病毒过程中具有重要作用，包括病毒基因组的细胞内运输，病毒RNA复制以及病毒基因组在后代病毒中的组装和包装。 流感A病毒NP的晶体结构最近在我们的实验室中确定[1]。 NP在晶体中以三聚体的形式组织成一个两域结构，其拓扑结构与色牛病毒NP完全不同（图2）。 由残基402至428组成的短尾循环在NP寡聚化中可能起重要作用，因为该区域的单递归突变会导致寡聚的总损失。在两个域之间的界面处的NP三聚体的外部确定了一个大带电的凹槽。外部RNA结合位点表明RNA可能在流感病毒RNP中暴露于与非细分RNA病毒的情况不同[2]。这种结构差异解释了先前的结果，该结果表明流感RNP与非细分（ - ） - 链RNA病毒（如VSV和狂犬病病毒）之间的基本差异。例如，流感病毒RNP中的病毒RNA通过RNase治疗消化，而副病毒病毒的RNP中的病毒RNA和犀牛病毒对RNase消化完全抗性[3-5]。 此外，带负电荷的聚合物聚乙烯基固定酸盐（PVS）能够完全从流感病毒RNP中置换RNA，而对VSV的RNP没有影响[6]。