RNA viruses cause several diseases such as AIDS, Ebola, and flu. These diseases kill millions each year and have the potential to erupt into pandemics that could infect the majority of the world’s population. As obligate intracellular parasites, viruses require cellular resources and machinery to reproduce so it is challenging to uncover ways to attenuate viral spread while leaving the host cells unharmed. Vesicular stomatitis virus (VSV) is a model RNA virus. A better understanding of its host interactions can provide potential insights into RNA virus treatment strategies. Caenorhabditis elegans are nematodes that have been widely used as models including for studies of metabolism disease, Alzheimer’s disease, and bacterial infection. C. elegans are an attractive model organism because they are inexpensive, have a short 3 day development period, are easy to genetically manipulate, and have homologues for about 60 percent of human genes. VSV and C. elegans will be combined to create a powerful model of virus-host interactions that will be able to examine interactions on multiple scales.
Reverse genetics techniques will be used to produce vesicular stomatitis virus strains of interest. These genetically defined virus strains will be characterized in a traditional mammalian cell culture system before being used to infect Caenorhabditis elegans primary cell culture and whole worms. Optimized conditions for viral infection will be determined and used to establish VSV and C. elegans as a virus-host model system. This model system will be used to measure the effects of virus-host interactions on an infection outcome. Measurements will be made on a single cell level, and these single cell measurements will be used to inform measurements of spreading virus infection.