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J. Virol., Nov 1995, 7152-7158, Vol 69, No. 11
SH Pincus, R Cole, R Ireland, F McAtee, R Fujisawa and J Portis
We have used an experimental retrovirus infection to study the roles played
by different antibodies in resistance to both infection and disease. A
molecularly cloned chimeric murine leukemia virus was used to induce acute
lethal neurological disease in neonatal mice. A panel of monoclonal
antibodies directed against the Gag and Env proteins was tested for
protective efficacy. In vitro neutralization assays demonstrated that
anti-Env antibodies gave different degrees of neutralization, while no
anti-Gag neutralized the virus. In vivo experimental endpoints were onset
of clinical signs and premoribund condition. As expected, different
anti-Env antibodies demonstrated different degrees of protection which
correlated with their neutralizing abilities. Surprisingly, anti-Gag
antibodies directed against both p15 (MA protein) and p30 (CA protein) were
also protective, significantly delaying the onset of disease. No protection
was seen with either of two control antibodies. The protection with
anti-Gag was dose related and time dependent and was also produced with Fab
fragments. Treatment with anti-Gag did not prevent viremia but resulted in
a slight slowing in viremia kinetics and decreased levels of virus in the
central nervous systems of mice protected from disease. These data indicate
that nonneutralizing antiretroviral antibodies can influence the outcome of
retroviral disease. The data also suggest a functional role for cell
surface expression of Gag proteins on murine leukemia virus-infected cells.
Copyright © 1995, American Society for Microbiology
Protective efficacy of nonneutralizing monoclonal antibodies in acute infection with murine leukemia virus
Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA.
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