A Search for the Regulators of Reproductive Aging in Caenorhabditis elegans

Pseudorabies virus (PRV) is an alphaherpesvirus of swine characterized by encephalomyelitis and inflammation of the respiratory tract causing severe epidemic outbreaks and economic losses. Efforts to eradicate PRV have elucidated the molecular mechanisms of herpesvirus pathogenesis and neuronal invasion, making PRV a powerful tool in exploring the neuroanatomical pathways of the brain, via its characteristic bidirectional and transneuronal spread. However, there is minimal literature on anterograde spread, stalling the development of treatment and prevention for this virus. PRV relies on Us9 for anterograde spread of newly replicated particles and sorting into lipid rafts. Many studies suggest that sphingolipids, significant lipid raft constituents, and sphingomyelinases are necessary for viral intracellular transport. I propose an examination of a host protein, SMPD4, a neutral sphingomyelinase involved in ceramide production and biogenesis of exosomes, and its interactions with Us9. SMPD4 was the second most enriched host protein associated with Us9 in an immunoprecipitation and massspectrometry experiment. These findings lead us to hypothesize that SMPD4 functions in PRV infection by interacting with Us9 in lipid rafts, and therefore is involved in anterograde movement. My work will explore relationships between these components through a series of western blots and immunofluorescence experiments, and contribute to knowledge of alphaherpesvirus pathogenesis, mammalian neuronal function, and veterinary medicine.