Molecular mimiicry in virus infection : Crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments ( monoclonal antibodies / vimentin / autoantibodies )

Abstract

Using monoclonal antibodies, we demonstrate that the phosphoprotein of measles virus and a protein of herpes simplex virus type 1 crossreact with an intermediate filament protein of human cells. This intermediate filament protein, probably vimentin, has a molecular weight of 52,000, whereas the molecular weights of the measles viral phosphoprotein and the herpes virus protein are 70,000 and 146,000, respectively. Crossreactivity was shown by immunofluorescent staining of infected and uninfected cells and by immunoblotting. The monoclonal antibody against measles virus phosphoprotein did not react with herpes simplex virus protein and vice versa, indicating that these monoclonal antibodies recognize different antigenic determinants on the intermediate filament molecule. The significance of these results in explaining the appearance of autoantibodies during virus infections in humans is discussed. Many mechanisms have been proposed to account for the induction of autoimmunity in humans. One plausible explanation is infection by virus. Viruses may induce autoimmune responses through shared determinants on molecules normally present on host cells, by altering the host immune system, or by causing the expression or release of "normally sequestered" self antigens. Autoantibodies are a frequent finding in the sera of virus-infected individuals, both during and after infection. For example, after infection with Epstein-Barr virus (1, 2), antibodies reacting with intermediate filaments of cells, immunoglobulin, or thyroglobulin were detected. Similarly, humans infected with hepatitis, herpes, mumps, or measles viruses can develop antibodies to their own cytoskeletal components (3-5), although the antibodies that reacted with cytoskeletal proteins were not shown to bind to viruses (5). Monoclonal antibodies (MAbs) provide probes to analyze unique determinants on viruses and on self constituents. Using such probes, we have described (6, 7) a MAb against herpes simplex type 1 virus (HSV-1) that reacts with a variety of uninfected mammalian cells. Furthermore, we have noted that a large proportion of MAbs originally derived by immunization of mice with measles virus polypeptides react with self constituents of human cells. We describe here two MAbs with dual specificity; one recognizes the phosphoprotein of measles virus and the intermediate filament protein, Mr 52,000. The other binds to and immunoprecipitates a protein present during the late phase of HSV infection (7) and reacts with a similar intermediate filament protein. The intermediate filaments are a normal component of uninfected cells. MATERIALS AND METHODS Cells, Virus, and Virus Infection. HeLa, Vero, BHK21, CV1, HEp-2, and human astrocyte cells were maintained in Eagle's minimal essential medium containing 10% fetal calf serum, 1% glutamine, and antibiotics. These cells were cultured in T75 flasks (Falcon) at 370C in 5% CO2 and passed twice weekly. Astrocytes derived from a human brain biopsy sample were positive for glial fibrillary acidic protein by immunofluorescent

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Cite this paper

@inproceedings{FujinamiMolecularMI, title={Molecular mimiicry in virus infection : Crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments ( monoclonal antibodies / vimentin / autoantibodies )}, author={Robert Shin Fujinami and Michael B. A. Oldstone and ZOFIA WROBLEWSKAt and HILARY KOPROWSKItt} }