title: Spread and pathogenic characteristics of a G-deficient rabies virus recombinant: an in vitro and in vivo study.
abstract: Rabies virus (RV), a highly neurotropic enveloped virus, is known to spread within the CNS by means of axonal transport. Although the envelope spike glycoprotein (G) of cell-free virions is required for attachment to neuronal receptors and for virus entry, its necessity for transsynaptic spread remains controversial. In this work, a G gene-deficient recombinant RV (SAD delta G) complemented phenotypically with RV G protein (SAD delta G+G) has been used 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 of stereotaxic inoculation into the rat striatum, infection is shown to be restricted to initially infected cells and not transferred to secondary neurons. 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.
authors.affiliation: Rabies Unit, Virology Department, Pasteur Institute, 25 rue du Dr Roux, 75724 Paris Cedex 15, France1.
authors.forename: Réza
authors.initials: R
authors.lastname: Etessami
authors.affiliation: Max-von-Pettenkofer Institute, Munich, Germany2.
authors.forename: Karl-Klaus
authors.initials: KK
authors.lastname: Conzelmann
authors.affiliation: Rabies Unit, Virology Department, Pasteur Institute, 25 rue du Dr Roux, 75724 Paris Cedex 15, France1.
authors.forename: Babak
authors.initials: B
authors.lastname: Fadai-Ghotbi
authors.affiliation: Veterans Administration Medical Center, East Orange, Newark, NJ, USA3.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Natelson
authors.affiliation: Rabies Unit, Virology Department, Pasteur Institute, 25 rue du Dr Roux, 75724 Paris Cedex 15, France1.
authors.forename: Henri
authors.initials: H
authors.lastname: Tsiang
authors.affiliation: Rabies Unit, Virology Department, Pasteur Institute, 25 rue du Dr Roux, 75724 Paris Cedex 15, France1.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Ceccaldi
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001921:Brain / Q000821:virology; D002478:Cells, Cultured; D004274:DNA, Recombinant; D004279:DNA, Viral; D004195:Disease Models, Animal; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000821:virology; D011817:Rabbits; D011818:Rabies / Q000473:pathology / Q000821:virology; D011820:Rabies virus / Q000235:genetics / Q000472:pathogenicity*; D051381:Rats; D014771:Virion
chemical_list: D004274:DNA, Recombinant; D004279:DNA, Viral