Antiviral activity of monoclonal antibodies specific for the internal proteins N and NS of rabies virus.

Monoclonal antibodies (MAbs) specific for the rabies virus nucleoprotein (N protein) and non-structural (NS) protein of the nucleocapsid were introduced into adherent cells (fibroblasts and neuroblastoma) by the scrape-loading technique. After the cells had reattached to the substrate, they were infected with rabies virus. Inhibition of infection was monitored by measuring the intracytoplasmic viral nucleocapsid accumulation with an enzyme immunoassay using anti-N protein rabbit serum and by measuring the release of infectious virus with the plaquing system. Seventeen MAbs defining the three independent antigenic sites on the N protein were able to decrease nucleocapsid accumulation and the release of infectious virus. The MAbs describing the two antigenic sites on NS protein also had an antiviral effect on ERA virus. When an anti-N MAb (0.5 ng per cell) was introduced into CVS-infected cells, virus inhibition was complete if the anti-N MAb was introduced between 0 and 5 h post-infection and ineffective beyond 9 h post-infection. The inhibition was dose-dependent. The MAbs could block virus multiplication either by 'neutralizing' newly translated N and NS proteins or by impairing the initial transcription of the genome.

[1]  C. Rupprecht,et al.  Antigenic diversity of the glycoprotein and nucleocapsid proteins of rabies and rabies-related viruses: implications for epidemiology and control of rabies. , 1988, Reviews of infectious diseases.

[2]  L. Otvos,et al.  Localization and immunological characterization of antigenic domains of the rabies virus internal N and NS proteins. , 1987, Virus research.

[3]  P. Perrin,et al.  The influence of the type of immunosorbent on rabies antibody EIA; advantages of purified glycoprotein over whole virus. , 1986, Journal of biological standardization.

[4]  T. Wiktor,et al.  Antigenic sites on the ERA rabies virus nucleoprotein and non-structural protein. , 1985, The Journal of general virology.

[5]  G. Wertz,et al.  Role of the nucleocapsid protein in regulating vesicular stomatitis virus RNA synthesis , 1985, Cell.

[6]  A. Portner,et al.  Structural and functional analysis of Sendai virus nucleocapsid protein NP with monoclonal antibodies. , 1984, Virology.

[7]  F. Superti,et al.  Mechanism of rabies virus entry into CER cells. , 1984, The Journal of general virology.

[8]  D. Taylor,et al.  A method for incorporating macromolecules into adherent cells , 1984, The Journal of cell biology.

[9]  R. Lazzarini,et al.  MICROINJECTION OF MONOCLONAL ANTIBODIES TO VESICULAR STOMATITIS VIRUS NUCLEOCAPSID PROTEIN INTO HOST CELLS: EFFECT ON VIRUS REPLICATION1 , 1984 .

[10]  H. Koprowski,et al.  Antigenic analysis of rabies and Mokola virus from Zimbabwe using monoclonal antibodies. , 1984, Developments in biological standardization.

[11]  G. Libeau,et al.  Production of monoclonal antibodies against the Pasteur (P.V.) strain of rabies virus: problems and results. , 1984, Developments in biological standardization.

[12]  T. Wiktor,et al.  Antigenic sites on the CVS rabies virus glycoprotein: analysis with monoclonal antibodies. , 1983, The Journal of general virology.

[13]  D. Summers,et al.  Synthesis of VSV RNPs in vitro by cellular VSV RNPs added to uninfected HeLa cell extracts: VSV protein requirements for replication in vitro. , 1982, Virology.

[14]  A. Banerjee,et al.  Production and characterization of a monoclonal antibody to the N protein of vesicular stomatitis virus (Indiana serotype). , 1982, Virology.

[15]  S. Harmon,et al.  Characterization of monospecific antisera against all five vesicular stomatitis virus-specific proteins: anti-L and anti-NS inhibit transcription in vitro. , 1982, Virology.

[16]  D. Boucher,et al.  Antigenic variants of rabies virus. , 1980, Comparative immunology, microbiology and infectious diseases.

[17]  J. Keene,et al.  The origins of defective interfering particles of the negative-strand RNA viruses , 1981, Cell.

[18]  M. Leppert,et al.  Interaction of VSV leader RNA and nucleocapsid protein may control VSV genome replication , 1981, Cell.

[19]  H. Koprowski,et al.  Antigenic variants of rabies virus , 1980, The Journal of experimental medicine.

[20]  H. Koprowski,et al.  Use of monoclonal antibodies in diagnosis of rabies virus infection and differentiation of rabies and rabies-related viruses , 1980 .

[21]  Charlton Km,et al.  Experimental rabies in skunks: immunofluorescence light and electron microscopic studies. , 1979 .

[22]  H. Koprowski,et al.  Monoclonal antibodies against rabies virus produced by somatic cell hybridization: detection of antigenic variants. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[23]  A. Carroll,et al.  Inhibition of transcription by immunoglobulins directed against the ribonucleoprotein of homotypic and heterotypic vesicular stomatitis viruses , 1978, Journal of virology.

[24]  F. Ruddle,et al.  Expression of neuronal phenotypes in neuroblastoma cell hybrids. , 1974, Developmental biology.

[25]  F. Murphy,et al.  Comparative pathogenesis of rabies and rabies-like viruses. Viral infection and transit from inoculation site to the central nervous system. , 1973, Laboratory investigation; a journal of technical methods and pathology.

[26]  H. Koprowski,et al.  Early events of rabies virus replicaton in tissue cultures. An electron microscopic study. , 1973, Laboratory investigation; a journal of technical methods and pathology.

[27]  T. Wiktor.  Laboratoty techniques in rabies: tissue culture methods. , 1973, Monograph series. World Health Organization.

[28]  D. Davies,et al.  The three-dimensional structure at 6 A resolution of a human gamma Gl immunoglobulin molecule. , 1971, The Journal of biological chemistry.

[29]  W. W. Nichols,et al.  Definition of a continuous human cell line derived from neuroblastoma. , 1970, Cancer research.

[30]  S. Bramhall,et al.  A simple colorimetric method for determination of protein. , 1969, Analytical biochemistry.

[31]  Kissling Re.  Growth of Rabies Virus in Non-Nervous Tissue Culture. , 1958 .

[32]  R. Kissling.  Growth of Rabies Virus in Non-Nervous Tissue Culture , 1958, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.