Characterization of P gene-deficient rabies virus: propagation, pathogenicity and antigenicity.
The RNA polymerase of rabies virus (RV) is a two-protein complex composed of L (a large catalytic component) and P (a non-catalytic phosphoprotein cofactor) proteins. We generated a gene-deficient RV lacking the entire P gene from HEP-Flury (HEP) strain, one of the most attenuated RV strains, by the method of reverse genetics. This P gene-deficient (def-P) virus could replicate and produce progeny viruses with a slightly retarded rate in the cell lines that constitutively express the P protein. The def-P virus could perform the primary RNA transcription by the virion-associated polymerase even in the infected host without de novo P protein synthesis. However, the def-P virus required the newly synthesized P protein for the secondary RNA transcription and genome RNA replication of virus. No progeny virus was produced in the infected host that did not express P protein. The def-P virus was apathogenic in adult and suckling mice even when inoculated intracranially. On the other hand, inoculation of the def-P virus into mice induced a high titer of virus-neutralizing antibody and protected mice from lethal challenge with the CVS strain. These results demonstrated that the def-P virus could induce strong protective immunity against rabies virus without the production of progeny virus and the severe host damage. The def-P virus would be a potential resource of safe live-attenuated rabies vaccine.
Morimoto
Kinjiro
K
Department of Virology I, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. kmorimot@nih.go.jp
Shoji
Youko
Y
Inoue
Satoshi
S
D000818:Animals; D003673:Defective Viruses / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D018832:Molecular Chaperones; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011820:Rabies virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D015678:Viral Structural Proteins / Q000172:deficiency* / Q000235:genetics; D014779:Virus Replication
D018832:Molecular Chaperones; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; D011819:Rabies Vaccines; D015678:Viral Structural Proteins