ResearchTracing the hardwiring of the nervous system with a virus
Unlike infections of the natural host (the adult pig), PRV infections of all other permissive
species (e.g., baby pigs, chicken embryos, rodents, dogs, cats, and cows, to name a few) are
lethal and quickly transmitted through peripheral nerves to the brain and spinal cord. These
infections enable us to study not only mechanisms of virulence and how the nervous system
responds to infection, but also how the virus spreads in the nervous system. Amazingly enough,
in all permissive species, the virus spreads only in chains of synaptically connected neurons
(trans-neuronal spread). Therefore, PRV can be used as a self-amplifying tracer of neuronal
circuits. The ability to reveal a neural circuit (neuron A is wired to neuron B is wired to
neuron C etc) is powerful technology, but demands attention to many details. Tracing studies
are rewarding because they require close collaboration between neurobiologists and virologists.
For example, circuit tracing requires use of mutant viruses that are much less virulent than
wild type PRV. Understanding why these mutants are good tracing strains has led us to a better
understanding of virulence and mechanisms by which virus spreads between neurons. In addition,
we capitalize on our ability to manipulate PRV to construct less virulent, innovative tracing
viruses: e.g., viruses expressing b-galactosidase and variants of green fluorescent protein,
as well as viruses that replicate only in certain neurons and not others. These viruses provide
powerful tools to study neural circuits and how the nervous system responds to infection. |