Fig. 5.

Ubiquitin switch model of herpesvirus neuroinvasion. The large tegument protein (pUL36) encodes a deubiquitinase (DUB) activity and a ubiquitin addition site (K442 in PRV), both of which are essential for virus invasion of the nervous system from peripheral tissues. The DUB and K442 acceptor site together constitute a molecular switch that alternates the virus between an axon targeting mode (state 1), and a sustained retrograde transport mode (state 2) that is required for the long-distance delivery of viral particles within nerve fibers to the peripheral ganglia.