The proposed research will examine the action of volatile inhalational anesthetics on the biochemistry of measles virus in vitro and on the pathogenesis of virus infections in patients undergoing surgery and anesthesia. Measles virus will be grown in tissue culture and exposed to various volatile inhalational anesthetics. The mechanism by which halothane, enflurane, or isoflurane affect viral macromolecular synthesis and maturation, especially protein synthesis and processing, will be investigated and compared to cellular protein synthesis and processing in uninfected cultures exposed and not exposed to the volatile anesthetics. We will determine whether anesthetic induced inhibition of protein synthesis occurs at the transcriptional and/or translational level. Anesthetic induced perturbations in phosphorylation and glycosylation of virus proteins will be examined. Anesthetic induced alterations in the levels of cellular mediators such as those which control phosphorylation and glycosylation will be assessed and correlated to observed changes in protein processing. It is believed these studies will help to elucidate the role that anesthetics play in inducing alterations in protein synthesis and processing by altering intracellular messenger levels and/or transduction during virus replication. The clinical studies to date in a pediatric population have suggested an important clinical and economical direction in the practice of anesthesia. The studies described in this proposal will continue and extend these experiments in an adult population who have an upper respiratory tract infection and are undergoing anesthesia for gynecological surgery. By correlating these in vivo results with our in vitro results we hope to establish a firm molecular basis for our clinical findings.
