The entry machinery of flaviviruses

Summary

We have been using the flavivirus tick-borne encephalitis virus (TBEV) as a model system for investigating the molecular mechanisms underlying the membrane fusion process mediated by a cla ss II viral fusion protein, the f1avivirus envelope protein E. In the mature virion this protein exi sts as a meta stable dimer that dissoci ates at the acidic pH in endosomes and is converted into a more stable trimeric conformation. The dimer dissociation step liberates an internal fusion peptide that interacts with the target endosomal membrane, and then further conformational change s are believed to drive membrane fusion. Although f1avivirus fusion appears to be a more fac ile and efficient process than that of alphaviruses, which also possess a class II viral fusion protein, the fusion mechanism in both viral systems involves structurally related interactions with lipids, specifically the 3;-hydroxyl group at C3 of cholesterol. The class 11 viral fusion machineries are structurally different from those involving cla ss I viral fusion proteins, such as those found in orthomyxoviruses, paramyxoviruses, retroviruses, and filoviruses, but have certain similarities in common with bacterial pore-forming proteins.