Rabies virus antinucleoprotein antibody protects against rabies virus challenge in vivo and inhibits rabies virus replication in vitro.
We previously reported that A/WySnJ mice vaccinated via a tail scratch with a recombinant raccoon poxvirus (RCN) expressing the rabies virus internal structural nucleoprotein (N) (RCN-N) were protected against a street rabies virus (D. L. Lodmell, J. W. Sumner, J.J. Esposito, W.J. Bellini, and L. C. Ewalt, J. Virol. 65:3400-3405, 1991). To improve our understanding of the mechanism(s) of this protection, we investigated whether sera of A/WySnJ mice that had been vaccinated with RCN-N but not challenged with street rabies virus had anti-rabies virus activity. In vivo studies illustrated that mice inoculated in the footpad with preincubated mixtures of anti-N sera and virus were protected. In addition, anti-N sera inoculated into the site of virus challenge protected mice. The antiviral activity of anti-N sera was also demonstrated in vitro. Infectious virus was not detected in cultures 24 h following infection with virus that had been preincubated with anti-N sera. At later time points, infectious virus was detected, but inhibition of viral production was consistently > or = 99% compared with control cultures. The protective and antiviral inhibitory activity of the anti-N sera was identified as anti-N antibody by several methods. First, absorption of anti-N sera with goat anti-mouse immunoglobulin serum, but not normal goat serum, removed the activity. Second, radioimmuno-precipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of sucrose density gradient-fractionated anti-N sera showed that antiviral activity was present only in the fraction containing anti-N antibody. Finally, absorption of anti-N sera with insect cells infected with a baculovirus expressing the N protein removed the protective activity. These data indicate that anti-N antibody is a component of the resistance to rabies virus infections.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.
D L
DL
Lodmell
J J
JJ
Esposito
L C
LC
Ewalt
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology*; D002685:Chiroptera; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006041:Goats / Q000276:immunology; D007116:Immunization, Passive; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D009698:Nucleoproteins / Q000276:immunology*; D011818:Rabies / Q000276:immunology*; D011819:Rabies Vaccines / Q000276:immunology*; D011820:Rabies virus / Q000276:immunology* / Q000302:isolation & purification; D011863:Radioimmunoassay
D000914:Antibodies, Viral; D000956:Antigens, Viral; D009698:Nucleoproteins; D011819:Rabies Vaccines