In response to the potential use of orthopoxviruses such as variola virus as a terrorist weapon, we propose to establish an Orthopoxvirus Genetic and Bioinformatics Resource Center that will collect, catalog, annotate, and analyze genetic information related to this virus genus. This work will expand on available knowledge of virus replication and virus-host interaction on a gene-by-gene and whole genome basis. This information will then be made available to the scientific community to support current research efforts to develop environmental detectors, diagnostics, antiviral compounds, new vaccines, and animal models. In support of these goals, we propose: 1. To develop a relational database that will support the data storage, annotation, analysis, and information exchange goals of this proposal. 2. To develop a world-wide web site that will allow all information and analytical results compiled and generated by this work to be publicized to the scientific community, providing rapid access to specific information as required by an individual researcher. 3. To collect existing gene and genomic sequences for orthopoxvirus species and import them into the database for subsequent annotation and analysis; to provide the capability to sequence portions of the genomes from existing and newly isolated orthopoxviruses for comparison with existing strains and species; and to provide a repository for live virus samples and virus clones for any newly isolated viruses that have been collected. 4. To provide computer-automated and human-directed annotation to confirm and update existing biological information in the sequence records for existing as well as newly obtained sequences; and to perform a variety of analyses on genome and gene sequences to provide additional information on their structure, function, and evolution.