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 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.
Etessami
Réza
R
Rabies Unit, Virology Department, Pasteur Institute, 25 rue du Dr Roux, 75724 Paris Cedex 15, France1.
Conzelmann
Karl-Klaus
KK
Max-von-Pettenkofer Institute, Munich, Germany2.
Fadai-Ghotbi
Babak
B
Rabies Unit, Virology Department, Pasteur Institute, 25 rue du Dr Roux, 75724 Paris Cedex 15, France1.
Natelson
Benjamin
B
Veterans Administration Medical Center, East Orange, Newark, NJ, USA3.
Tsiang
Henri
H
Rabies Unit, Virology Department, Pasteur Institute, 25 rue du Dr Roux, 75724 Paris Cedex 15, France1.
Ceccaldi
Pierre-Emmanuel
PE
Rabies Unit, Virology Department, Pasteur Institute, 25 rue du Dr Roux, 75724 Paris Cedex 15, France1.
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
D004274:DNA, Recombinant; D004279:DNA, Viral