Structure/function studies of adenovirus capsid protein IX

点击翻译按钮获取中文摘要

Viruses are very good at delivering their DNA into cells, and this observation has been exploited to develop highly-attenuated viruses (no longer cause disease) that can deliver any gene-of-interest to cells in the laboratory for experimental study. In this application, we will continue our research program dedicated to improving our understanding of basic aspects of Ad biology that contributes to its function as an efficient gene delivery system. Our current work is focused on a viral protein, called protein IX. This protein is directly involved in helping the virus gain entry into the cell, and also appears to have a second function in reducing the effectiveness of the cell's natural defenses against infection. We will determine the mechanism of how the virus and protein are capable of doing this, which will provide novel insight into anti-viral proteins within the cell and how viruses interact with them. Recently, we showed that we could modify protein IX in order to target virus infection to specific cell types, such as cancer cells. However, although delivery was effective, these viruses now have a reduced ability to carry normal amounts of DNA, for reasons which are unclear. We will determine the nature of this deficiency and explore methods to correct it. Taken together, our current work on pIX will provide insight into virus structure, infection, and replication, and will also elucidate cellular proteins that act as anti-viral defense factors, further highlighting the ongoing battle between host and pathogen. In addition, we will refine our ability to produce Ad-based gene delivery systems that can be targeted to specific cell types and tissues, which ultimately will benefit many researchers utilizing Ad as a gene delivery tool.