A novel membrane fusion protein family in Flaviviridae?

Enveloped viruses must fuse their lipid membrane to a cellular membrane to deliver their genome into the cytoplasm for replication. Viral envelope proteins catalyze this critical membrane fusion event. They fall into three distinct structural classes. In 2013, envelope proteins from a pestivirus and hepatitis C virus were found to have two distinct novel folds. This was unexpected because these viruses are in the same family as flaviviruses, which have class II fusion proteins. We propose that the membrane fusion machinery of the closely related pestiviruses and hepatitis C virus defines a new structural class. This and other recently identified structural relationships between viral fusion proteins shift the paradigm for how these proteins evolved.