Encapsidation of adenovirus DNA

腺病毒是一种小的、无包膜的病毒，包含一个线性双链DNA基因组，于1953年首次被发现。人类腺病毒与多种疾病有关，包括上呼吸道感染、胃肠道疾病和结膜炎。腺病毒感染是移植受者，特别是儿科患者的一个重大临床问题。多年来，这些病毒也一直 研究DNA复制、RNA合成、蛋白质翻译、致癌转化和细胞凋亡的优秀模型系统，以及最近对腺病毒的兴趣已经扩大，因为它作为疫苗接种和人类基因转移研究的载体的潜力已经扩大。病毒基因表达、基因组复制和病毒 所有的组装都发生在受感染细胞的细胞核内。这个项目致力于组装病毒DNA的封装。这个过程至少需要四个病毒元件：位于基因组左端的包装序列，由称为A重复的重复元件组成；IVa2蛋白，它与该区域所需的序列基序结合，也是衣壳组装所必需的；L422 kDa蛋白，它与DNA上的IVa2蛋白形成复合体；以及52/55 kDa蛋白，它结合DNA和IVa2蛋白。这项建议的目的是进一步阐明腺病毒包裹其dna的机制，以及这一过程如何与衣壳的形成有关。 IVa2蛋白。IVa2蛋白促进衣壳组装和DNA包装的机制将通过检查包含IVa2和L4 22 kDa蛋白的复合体的结构和解剖IVa2蛋白的各种功能来研究。52/55 kDa蛋白的作用也将通过对突变病毒的分析来揭示。这些研究将促进我们对腺病毒如何 包装它的DNA并产生具有传染性的病毒粒子。这一知识将适用于阻止这一过程的抗病毒药物的开发，以及更安全的腺病毒载体和重组疫苗的开发。

Adenoviruses are small, non-enveloped viruses containing a linear double stranded DNA genome that were first discovered in 1953. The human adenoviruses are associated with a variety of diseases including upper respiratory infections, gastrointestinal illness, and conjunctivitis. Adenovirus infections are a significant clinical problem in transplant recipients, particularly pediatric patients. For many years, these viruses have also been outstanding model systems for the study of DNA replication, RNA synthesis, protein translation, oncogenic transformation, and apoptosis, and more recently interest in adenovirus has expanded due to its potential as a vector for vaccination and human gene transfer studies. Viral gene expression, genome replication, and viral assembly all take place in the nucleus of the infected cell. This project addresses assembly with a focus on the encapsidation of viral DNA. This process requires at least four viral elements: the packaging sequence, which is located near the left end of the genome and is made up of repeated elements called A repeats; the IVa2 protein, which binds to required sequence motifs in this region and is also required for capsid assembly; the L4 22 kDa protein, which forms a complex with the IVa2 protein on the DNA; and the 52/55 kDa protein, which binds both the DNA and the IVa2 protein. The goals of this proposal are to elucidate further the mechanism by which adenovirus encapsidates its DNA, and how this process is linked to capsid formation by the IVa2 protein. The mechanism by which the IVa2 protein facilitates capsid assembly and DNA packaging will be studied by examining the structure of complexes containing the IVa2 and L4 22 kDa proteins and by dissecting the various functions of the IVa2 protein. The role of the 52/55 kDa protein will also be uncovered through the analysis of mutant viruses. These studies will advance our basic understanding of how adenovirus packages its DNA and produces infectious virions. This knowledge will be applicable to the development of anti-viral drugs that block this process, as well as to the development of safer adenovirus vectors and recombinant vaccines.