STRUCTURAL STUDIES OF SSDNA VIRUSES AND VIRAL PROTEINS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 我们的研究ssDNA病毒的目的是确定受体附着，组织嗜性，在体内的致病性，和高度同源的细小病毒科菌株和血清型之间的转导效率的结构决定因素。迄今为止，我们的结构研究表明，轻微的衣壳表面的变化，导致氨基酸的差异，与细小病毒的病毒生命周期中的生物学特性的显着差异。我们的长期目标是利用所获得的结构信息设计病毒疫苗、外源抗原递送系统和用于治疗动物和人类疾病的病毒基因治疗载体。 我们希望获得用于收集用于基因治疗应用的腺相关病毒血清型AAV 5、AAV 8和AAV 9的数据的实验射束时间以及小鼠微小病毒（MVMp）的原型株。我们的目的是收集关于AAV 9的天然数据，其没有结构信息，AAV 5和MVMp与其细胞表面受体的唾液酸化三糖组分共结晶，以及AAV 8和MVMp在模拟内体条件的pH下。wt AAV 5、AAV 8和MVMp的结构已经用来自各种同步加速器源（包括NSLS的X29）的数据确定。

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. Our studies on ssDNA viruses are aimed at identifying structural determinants of receptor attachment, tissue tropism, in vivo pathogenicity, and transduction efficiencies between highly homologous Parvoviridae strains and serotypes. Our structural studies so far indicate that slight capsid surface alterations, resulting from amino acid differences, are associated with pronounced differences in biological properties during the viral life cycle of parvoviruses. Our long-term goals are to utilize the structural information obtained for the design of viral vaccines, foreign antigenic delivery systems, and viral gene therapy vectors for the treatment of animal and human diseases. We wish to obtain experimental beam time for data collection on the Adeno-associated virus serotypes AAV5, AAV8 and AAV9¿¿"being exploited for gene therapy applications and the prototype strain of minute virus of mice (MVMp). We aim to collect native data on AAV9 for which there is no structural information, AAV5 and MVMp co-crystallized with sialylated trisaccharide components of their cell surface receptors and AAV8 and MVMp at pHs that mimic endosomal conditions. The structures of wt AAV5, AAV8 and MVMp have already been determined with data from various synchrotron sources, including X29 at NSLS.