Targeting of herpesvirus capsid transport in axons is coupled to association with specific sets of tegument proteins

The capsids of neurotropic herpesviruses have the remarkable ability to move in specific directions within axons. By modulating bidirectional capsid transport to favor either retrograde (minus-end) or anterograde (plus-end) motion, these viruses travel to sensory ganglia or peripheral tissue at specific stages of infection. By using correlative motion analysis to simultaneously monitor the trafficking of distinct viral proteins in living neurons, we demonstrate that viral "tegument" proteins are complexed to capsids moving in axons. The removal of a subset of tegument proteins from capsids invariably preceded retrograde transport to the cell body in sensory ganglia, whereas addition of these proteins was coupled to anterograde transport of progeny capsids to the distal axon. Although capsid transport never occurred without associated tegument proteins, anterograde-specific tegument proteins were competent to travel to the distal axon independent of capsids. These findings are compatible with a model of viral bidirectional transport in which tegument proteins direct capsid traffic to specific intracellular locations during the infectious cycle.