Generation and characterization of P gene-deficient rabies virus

Virology. 2004 Jan 5;318(1):295-305. doi: 10.1016/j.virol.2003.10.001.


Rabies virus (RV) deficient in the P gene was generated by reverse genetics from cDNA of HEP-Flury strain lacking the entire P gene. The defective virus was propagated and amplified by rescue of virus, using a cell line that complemented the functions of the deficient gene. The P gene-deficient (def-P) virus replicated its genome and produced progeny viruses in the cell lines that constitutively expressed the P protein, although it grew at a slightly retarded rate compared to the parental strain. In contrast, no progeny virus was produced in the infected host when the def-P virus-infected cells that did not express the P protein. However, we found that the def-P virus had the ability to perform primary transcription (by the virion-associated polymerase) in the infected host without de novo P protein synthesis. The def-P virus was apathogenic in adult and suckling mice, even when inoculated intracranially. Inoculation of def-P virus in mice induced high levels of virus-neutralizing antibody (VNA) and conferred protective immunity against a lethal rabies infection. These results demonstrate the potential utility of gene-deficient virus as a novel live attenuated rabies vaccine.

MeSH terms

  • Animals
  • Animals, Suckling
  • Antibodies, Viral / blood
  • Base Sequence
  • Cell Line
  • Cricetinae
  • Defective Viruses / genetics*
  • Defective Viruses / immunology
  • Defective Viruses / pathogenicity
  • Defective Viruses / physiology
  • Immunization
  • Mice
  • Mice, Inbred ICR
  • Molecular Sequence Data
  • Neutralization Tests
  • Rabies / prevention & control*
  • Rabies / virology
  • Rabies Vaccines* / administration & dosage
  • Rabies Vaccines* / genetics
  • Rabies Vaccines* / immunology
  • Rabies virus / genetics*
  • Rabies virus / immunology
  • Rabies virus / pathogenicity
  • Rabies virus / physiology
  • Tumor Cells, Cultured
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism
  • Virus Replication


  • Antibodies, Viral
  • Rabies Vaccines
  • Viral Proteins