Vesicular Stomatitis Virus

Electron micrograph of vesicular stomatitis virus particles

Evolution of virus specialists and generalists

Arthropod-borne viruses (arboviruses) are able to infect arthropods (insects, ticks) as well as other host organisms. For this reason, arboviruses typically encounter alternating host environments in the wild, and have evolved to feature very broad host ranges. We use the RNA arbovirus vesicular stomatitis virus (VSV) as a model to examine the evolutionary and molecular genetics of host adaptation.

One study allowed VSV to evolve on either of two novel hosts (selection for specialist viruses), or in environments where the two novel hosts fluctuated in time (selection for generalist viruses) (Turner and Elena 2000, Genetics 156:1465-1470). Specialists evolved increased performance on the novel host, at the expense of reduced performance in the alternate host. In contrast, generalists improved their fitness in both novel habitats. These findings contradict the idea that weaker response to selection causes generalists to be disadvantaged relative to specialists.

Current work examines the evolution of genetic architecture in our collection of derived specialists and generalists (Remold et al. 2008, Mol Biol Evol 25:1138-1147). How do these differing phenotypes map at the molecular level? Are genomic changes in each group highly conserved? Alternatively, do differing adaptive solutions to the same environmental challenges cause populations in each group to genetically diverge? Ongoing research examines the importance of spatially-structured environments in the evolution of VSV, and differing rates of adaptation in specialist and generalist viruses.

Evolutionary Interactions between RNA Viruses and Cancer Cells

Vesicular stomatitis virus (VSV) and other viruses are being developed as novel anti-cancer (oncolytic virus) therapies, where viruses target and destroy tumors. Our work showed that changes in the matrix protein of VSV coincided with evolutionary specialization of viruses on cancer-derived cells (Remold et al. 2008, Mol Biol Evol 25:1138-1147). We are currently using reverse genetics in VSV to determine whether these candidate beneficial mutations interact with other allele substitutions via epistasis. In addition, we are merging experimental evolution with systems biology to study how ecological history (evolution in presence vs. absence of cancer cells) affects VSV ability to control intracellular apoptotic networks and to resist innate cellular immunity. Other ongoing studies examine the effects of ecological history and genetic architecture (order of genes in the VSV genome), in the subsequent ability for VSV lineages to adapt to novel cancer-cell types.

Evolution of Host Shifts and Emergence

The emergence of RNA viruses in humans and other hosts presents increasing challenges in medicine, public health, agriculture and conservation biology. We are examining how prior ecological history (evolution on single vs. multiple hosts) affects the ability for viruses to emerge on novel hosts (Turner et al. 2010, Evolution 64:3273-3286). Ongoing projects concern the consequences of virus adaptation to new hosts, and how evolved host-use affects virus performance under radically different challenges, such as growth at extreme temperatures (Alto and Turner, Evolutionary Ecology 24:299-315). These empirical results can be combined with mathematical theory, to generally predict how current host-use breadth impacts the future probability that a virus will successfully emerge on a novel host (Ogbunugafor et al. 2010. Phil. Trans. R. Soc. B 365:1919-1930).