Presentation description

Poxviruses infect many species, including humans. During infections, poxviruses sometimes "steal" genes from their hosts by incorporating them into their own DNA, including interferon-stimulated genes (ISGs) that, in host cells, activate immune responses. In viral genomes, genes encoding these proteins can counterattack the host's defenses or even prevent the host cell from recognizing the virus. However, virus genes can evolve rapidly, and the identity of "stolen" genes and how they interact with host immune systems can be hard to observe. In order to discover interactions between viral and host immune proteins, we used AlphaFold Multimer to screen human ISG proteins and poxvirus proteins to predict novel interactions between these proteins. Among a collection of newly proposed interactions, the highest confidence interface was predicted between the host protein fractalkine and the cowpox viral protein interleukin 18 binding protein (viral IL-18 BP). In our investigations, we will use biochemical approaches to test physical interactions, and we have had early success expressing both proteins as judged by western blots. To test the interaction between fractalkine and viral IL-18 BP, we plan to do co-immunoprecipitation assays to determine if fractalkine does truly interact with the viral IL-18 BP. We are also aligning amino acid sequences and building phylogenetic trees of IL-18, IL-18 BP, and fractalkine to better understand evolutionary relationships between these proteins in primates. Comparing these sequences will also provide a better understanding of selective pressures influencing the evolution of these immune genes.