Only cells with Us9 (top) get viral membrane proteins into axons.

Reactivated herpes viruses make their way from the nerve cell body to the axon terminal, where they are either shed or transferred across the synapse to another neuron. Tomishima and Enquist report on page 741 that, during this process, viral membrane proteins are transported into the axon independently of viral capsids, suggesting that viral assembly must occur at or near the synapse.

Viral assembly was thought to occur only in the cell body, with subsequent transport of fully assembled virions to axon terminals for release. Indeed, a pseudorabies virus mutant for Us9 appeared to be defective only in the second step, as it still makes infectious viral particles in the cell body but is defective for viral shedding from axons. But Tomishima and Enquist find that in the Us9 mutant some of the viral capsids are transported into the axon, leaving the viral membrane proteins behind in the cell body.

Us9 has motifs suggesting that it could interact with a neuron-specific adaptor, thus creating an axonal transport vesicle for viral membrane proteins. Segregating viral membrane proteins from viral capsids during axonal transport may ensure that virus components can reach the axon terminal without prematurely uniting and being shed as assembled virus. Perhaps when the components reach the synapse they encounter a synapse-specific protein that finally allows them to join together to form infectious particles. ▪