Spread and pathogenic characteristics of a G-deficient rabies virus recombinant: an in vitro and in vivo study

Rabies virus (RV), a highly neurotropic enveloped virus, is known to spread within the CNS by means of axonal transport. Although the envelope spike g lycoprotein (G) of cell-free virions is required for attachment to neuronal receptors and for virus entry, its necessity for transsynaptic spread rema ins controversial. In this work, a G gene-deficient recombinant RV (SAD BG) complemented phenotypically with RV G protein (SAD Delta G+G) has been use d to demonstrate the absolute requirement for G in virus transfer from one neuron to another, both in vitro, in neuronal cell cultures (cell line and primary cultures), and in vivo, in murine animal models. By using a model o f stereotaxic inoculation into the rat striatum, infection is shown to be r estricted to initially infected cells and not transferred to secondary neur ons. In mouse as in rat models of infection, the limited infection did not cause any detectable symptoms, suggesting that G-deficient RV recombinants might be valuable as non-pathogenic, single-round vectors for expression of foreign genes.