Characterization of the interaction between the herpes simplex virus type I Fc receptor and immunoglobulin G

Herpes simplex virus type I (HSV-1) virions and HSV-1-infected cells bind t o human immunoglobulin G (hIgG) via its Fc region. A complex of two surface glycoproteins encoded by HSV-1, gE and gI, is responsible for Fc binding. We have co-expressed soluble truncated forms of gE and gf in Chinese hamste r ovary cells. Soluble gE-gI complexes can be purified from transfected cel l supernatants using a purification scheme that is based upon the Fc recept or function of gE-gI. Using gel filtration and analytical ultracentrifugati on, we determined that soluble gE-gI is a heterodimer composed of one molec ule of gE and one molecule of gI and that gE-gI heterodimers bind hIgG with a 1:1 stoichiometry. Biosensor-based studies of the binding of wild type o r mutant IgG proteins to soluble gE-gI indicate that histidine 435 at the C (H)2-C(H)3 domain interface of IgG is a critical residue for IgG binding to gE-gI, We observe many similarities between the characteristics of IgG bin ding by gE-gI and by rheumatoid factors and bacterial Fc receptors such as Staphylococcus aureus protein A. These observations support a model for the origin of some rheumatoid factors, in which they represent anti-idiotypic antibodies directed against antibodies to bacterial and viral Fc receptors.