ORTHOPOXVIRUS GENOMICS AND BIOINFORMATICS RESOURCE CENTE

在可能用于生物恐怖主义的潜在生物中，天花可能对美国的健康产生最可怕的影响。天花具有高度传染性，死亡率在30%左右。没有可用的抗病毒治疗。此外，美国人口基本上是完全易感的，因为常规免疫接种在20世纪60年代初被终止。即使是较老的疫苗也很脆弱，因为疫苗的保护作用在十年后会显著减弱。由于这种疾病的根除，除了鸡痘疫苗载体的开发外，对天花和相关痘病毒的研究数量已大大减少。该提案将支持正痘病毒基因组信息的获取和分析，以促进其应用于开发天花和相关病毒的疗法和改进的疫苗。该项目的目标是：1）收集和/或确定可能作为动物模型中天花病毒替代物的天花病毒分离株和正痘病毒的基因组序列; 2）设计和维护关系数据库，以存储、显示、注释和查询基因组序列、结构信息、表型数据（如药物敏感性、毒力、宿主特异性）和文献信息; 3）应用创新方法对病毒基因组进行全球功能分析; 4）作为一个资料充分的病毒株（包括临床分离株和突变株，如果相关）和基因组序列分析中使用的基因组克隆库;和5）开发和维护一个网站。

Of the potential organisms that might be used in bioterrorism, smallpox would likely have the most horrific impact on the health of the U.S. Small pox is highly Contagious and mortality is in the range of 30%. There is no available antiviral therapy. Furthermore, the U.S. population is essentially entirely susceptible because routine immunization was terminated in the early 1960's. Even older vaccines are vulnerable as vaccine protection wanes significantly after ten years. As a result of the eradication of the disease, and with the exception of the development of fowlpox vaccine vectors, the amount of research on smallpox and related poxviruses has decreased significantly. This proposal will support the acquisition and analysis of orthopoxvirus genomic information to facilitate its application to the development of therapies and improved vaccines for smallpox and related viruses. The goals of the project are: 1) Collect and/or determine the genomic sequences of variola virus isolates and orthopoxviruses that might serve as surrogates for variola virus in animal models; 2) Design and maintain a relational database to store, display, annotate and query genome sequence, structural information, phenotypic data (e.g. drug susceptibility, virulence, host specificity) and bibliographic information; 3) Apply innovative methods for global functional analysis of the viral genomes; 4) Serve as a repository of well-documented viral strains (including clinical isolates and mutants, if relevant) and genomic clones that are used in the genomic sequence analysis; and 5) Develop and maintain a website.