Use of rabies virus as a transneuronal tracer of neuronal connections: implications for the understanding of rabies pathogenesis.
In neurosciences, rabies virus (CVS strain) has become a very powerful tool for studying multisynaptic neuronal connections, due to its ability to function as a self-replicating marker and to propagate exclusively between connected neurons by transneuronal transfer, which is strictly time-dependent. In this laboratory, transneuronal tracing studies of rabies virus propagation in primates and rodent models during the asymptomatic period have provided valuable information on rabies pathogenesis. We have shown that rabies virus propagates by fast axonal transport at similar speeds in primates and rodents, after inoculation into the peripheral or central nervous system (CNS). Intracellulartransport of rabies virus is preferentially addressed to neuronal dendrites rather than axons, since transneuronal transfer occurs only retrogradely, i.e., from dendrites of first infected neurons to presynaptic terminals of connected neurons. Rabies virus propagation occurs at chemical synapses, but not via gap junctions or local spread. The results of our studies show that rabies virus receptors have a ubiquitous distribution on neurons within the CNS. Conversely, in the peripheral nervous system, rabies virus receptors are present only on motor endings, since uptake is restricted to motor endplates and axons, whereas sensory and autonomic endings are not infected. Thus, after peripheral inoculations, motoneurons are the only gateway for rabies virus transmission to the CNS. Infection of sensory and autonomic neurons requires longer incubation times, since it reflects centrifugal propagation of rabies virus from the CNS to the periphery, i.e., it is the result of retrograde transneuronal transfer to sensory and autonomic terminals within the CNS.
Ugolini
G
G
Laboratoire Neurobiologie Cellulaire et Moléculaire (NBCM, UPR9040), CNRS, Gif-sur-Yvette, France. gabriella.ugolini@nbcm.cnrs-gif.fr
D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000821:virology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007700:Kinetics; D008251:Macaca; D009415:Nerve Net / Q000166:cytology* / Q000502:physiology / Q000821:virology; D009434:Neural Pathways / Q000166:cytology* / Q000502:physiology / Q000821:virology; D009474:Neurons / Q000821:virology*; D011818:Rabies / Q000473:pathology* / Q000821:virology; D011820:Rabies virus / Q000502:physiology*; D051381:Rats; D012680:Sensitivity and Specificity