Exploiting circuit-specific spread of pseudorabies virus in the central nervous system: Insights to pathogenesis and circuit tracers

The neurotropic alpha-herpesviruses are common mammalian pathogens that invade the peripheral and central nervous system of their hosts. Their ability to invade and spread in the nervous system in a directional manner has been exploited to develop them as neuronal circuit tracers. Tracing viruses spread among synaptically connected neurons and, by assaying brain sections for viral antigen or reporter genes expressed from the viruses, chains of synaptically connected neurons can be visualized. Virulent field strains generally are not good tracers, but some attenuated strains perform well. Live attenuated vaccine strains of pseudorabies virus (PRV), such as PRV Bartha, are among the most popular virus circuit tracers. It may be counterintuitive that attenuation results in improved neural tracing that requires extensive replication and spread in the brain. This report summarizes two lines of experiments directed to resolving this apparent paradox and introduces a new paradigm for tracing viruses.