FIG. 2

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In vivo models. The organization of neuronal circuitry in the two models used to evaluate viral invasiveness and replication in single- and dual-injection paradigms is illustrated. (Left panel) The ability of PRV to invade the nervous system via anterograde transneuronal infection was assessed in visual circuitry. In this model, virus is injected into the vitreous body of the eye, where it invades and replicates within retinal ganglion cells. Progeny virus is transported anterogradely through axons of the ganglion cells to produce transynaptic infection of neurons in the brain that receive visual input. Prior studies have demonstrated that subdivisions of this circuitry are differentially susceptible to infection by different strains of PRV, such that PRV-Bartha infects only a functionally distinct subset of retinal ganglion cells and their target neurons in the brain (11). (Right panel) Caudal brain stem neurons involved in the regulation of visceral function provided the model system for evaluating retrograde infection of the CNS. In this model, inoculation of the ventral wall of the stomach produces a retrograde infection of preganglionic parasympathetic neurons in the DMV of the caudal brain stem. Replication of virus in the DMV is followed by retrograde transynaptic infection of neurons in the adjacent NST and other synaptically linked neurons, including a population in the PVN (see Fig. Fig.6G).6G). It is well established that this circuitry is susceptible to all strains of PRV studied to date, including PRV-Bartha and related strains. dm, dorsomedial; vl, ventrolateral; DGN, dorsal geniculate nucleus; VGN, ventral geniculate nucleus; NG, nodose ganglion.

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