Evidence for antigenic cross-reactivity between herpesvirus and the acetylcholine receptor

Herpes simplex virus (HSV) is neurotropic and can pass from neuron to neuron at nerve terminals. During the long evolutionary relationship between HSV and vertebrates, this virus may have evolved surface ligands that mimic nerve cell receptors. The present study was undertaken to determine if herpes simplex virus type 1 (HSV-1) has an antigenic relationship with the acetylcholine receptor (AChR). Mice immunized with HSV-1 antigens or an AChR-expressing cell line were tested for antibodies directed against the AChR. By flow cytometry and ELISA, mouse anti-HSV-1 sera were found to contain antibodies that would bind to an epitope on the plasma membrane of AChR-expressing cells. Mice immunized with the AChR-expressing cells were tested for their resistance to HSV-1 infection. Statistically significantly more of the animals immunized with AChR-expressing cells resisted infection and fatal encephalitis, compared to control animals immunized with a cell line not expressing the AChR. Sera from AChR-immunized mice were tested for anti-HSV antibody by ELISA and were found to contain antibodies cross-reactive with HSV-1 antigens. These sera also neutralized virus in a plaque inhibition assay. The results indicate that there are one or more antigenic epitopes shared by herpesvirus and the AChR. Studies are in progress to define the pathogenetic significance of this molecular mimicry.