Abstract: The invention encompasses compositions and methods relating to viral polymerases having one or more substitutions of different amino acids at conserved regions of the polymerase yields enzymes with varying rates and fidelity of replication. A universally applicable, polymerase-mechanism-based strategy for production of attenuated viruses and anti-viral vaccines is disclosed. Attenuated viruses serve as vaccines and were shown to provide protection against poliovirus challenge in vivo.

Abstract: Ligands for the nuclear hormone receptor PPAR&ggr; significantly reduced the immunological symptoms of allergic asthma in a murine model of this disease. In vitro, 15-deoxy-Delta(12,14)-prostaglandin J(2), a PPAR&ggr; ligand, significantly inhibited production of the TH2 type cytokine IL-5 from T cells activated in vitro. More importantly, in a model of allergic asthma, mice treated orally with Ciglitazone had significantly reduced lung inflammation and mucous production following induction of allergic asthma. T cells from Ciglitazone treated mice also produced less IFN&ggr;, IL-4 and IL-2 upon rechallenge in vitro with the model allergen. Our results suggest that ligands for PPAR&ggr; may be effective treatments for asthmatic patients.