A conserved alpha-herpesvirus protein necessary for axonal localization ofviral membrane proteins

Pseudorabies virus, an a-herpesvirus, is capable of infecting the nervous s ystem and spreading between synaptically connected neurons in diverse hosts . At least three viral membrane proteins (gE, gI, and Us9) are necessary fo r the spread of infection from presynaptic to postsynaptic neurons (anterog rade spread) in infected rodents. To understand how these proteins effect a nterograde spread between neurons, we analyzed the subcellular localization of viral proteins after infection of cultured rat sympathetic neurons with wild-type or mutant viruses. After Us9-null mutant infections but not gE-n ull mutant infections, only a subset of the viral structural proteins had e ntered axons. Surprisingly, capsid and tegument proteins but not viral memb rane proteins were detected in axons. The spread of Us9 missense mutants in the rodent nervous system correlated with the amount of viral membrane pro teins localized to axons. We conclude that the Us9 membrane protein control s axonal localization of diverse viral membrane proteins but not that of ca psid or tegument proteins. The data support a model where virion subassembl ies but not complete virions are transported in the axon. Our results provi de new insight into the process of virion assembly and exit from neurons th at leads to directional spread of herpesviruses in the nervous system.