A novel protein-folding function of RNA has been recognized, which can outperform previously known molecular chaperone proteins.TheRNAas amolecular chaperone (chaperna) activity is intrinsic tosome ribozymesand is operational during viral infections.Our purposewasto testwhether influenzahemagglutinin (HA) canbe assembled in a soluble, trimeric, and immunologically activating conformation by means of an RNA molecular chaperone (chaperna) activity.AnRNA-interactingdomain (RID) fromthehostbeingimmunizedwas selected as adocking tag for RNAbinding,which served as a transducer for the chaperna function for de novo folding andtrimeric assembly ofRIDHA1. Mutations that affect tRNA binding greatly increased the soluble aggregation defective in trimer assembly, suggesting thatRNAinteraction critically controls thekinetic networkinthe folding/assemblypathway.Immunization of mice resulted in strong hemagglutination inhibition and high titers of a neutralizing antibody, providing sterile protection against a lethal challenge and confirming the immunologically relevantHA conformation. The results may be translated into a rapid response to anewinfluenzapandemic.Theharnessing of thenovel chaperna described herein with immunologically tailored antigen-folding functions should serve as a robust prophylactic and diagnostic tool for viral infections.
All Science Journal Classification (ASJC) codes
- Molecular Biology