       Document 0384
 DOCN  M9620384
 TI    Protective efficacy of nonneutralizing monoclonal antibodies in acute
       infection with murine leukemia virus.
 DT    9602
 AU    Pincus SH; Cole R; Ireland R; McAtee F; Fujisawa R; Portis J; Laboratory
       of Microbial Structure and Function, Rocky Mountain; Laboratories,
       National Institute of Allergy and Infectious; Diseases, Hamilton,
       Montana 59840, USA.
 SO    J Virol. 1995 Nov;69(11):7152-8. Unique Identifier : AIDSLINE
       MED/96013819
 AB    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.
 DE    Animal  Animals, Newborn  Antibodies, Monoclonal/*THERAPEUTIC USE
       Antibodies, Viral/THERAPEUTIC USE  Comparative Study  Fluorescent
       Antibody Technique, Indirect  Gene Products, env/IMMUNOLOGY  Gene
       Products, gag/IMMUNOLOGY  Immunoglobulins, Fab/THERAPEUTIC USE
       *Leukemia Viruses, Murine  Mice  Mice, Inbred Strains  Nervous System
       Diseases/*IMMUNOLOGY/PREVENTION & CONTROL/  *VIROLOGY  Neutralization
       Tests  Rats  Retroviridae Infections/*IMMUNOLOGY/PREVENTION & CONTROL
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes/IMMUNOLOGY  Time Factors  Tumor Virus
       Infections/*IMMUNOLOGY/PREVENTION & CONTROL  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

