ROLES OF IMMUNOGLOBULIN VALENCY AND THE HEAVY-CHAIN CONSTANT DOMAIN IN ANTIBODY-MEDIATED DOWN-REGULATION OF SINDBIS VIRUS-REPLICATION IN PERSISTENTLY INFECTED NEURONS

Clearance of infectious Sindbis virus from neurons is mediated by anti body to the E2 glycoprotein. Properties of the antibody important for downregulation of Sindbis virus replication are unknown. Immunoglobuli n isotypes and valency determine many biological properties of antibod ies. An immunoglobulin G1 (IgG1) isotype switch mutant and F(ab')(2) a nd Fab Fragments of IgG3 monoclonal antibody 209 were prepared and tes ted for clearance of infectious virus from persistently infected rat d orsal root ganglion neurons in vitro. IgG1, IgG3, and IgG3-derived F(a b')(2) fragments were similarly efficacious, while IgG3-derived Fab fr agments had no effect on virus replication. Cross-linking of Fab with secondary antibodies restored antiviral activity. Therefore, we found no evidence that IgG subclass plays a role in control of intracellular Sindbis virus replication. However, bivalency appears to be crucial f or the ability of E2 specific IgG molecules to mediate clearance of in fectious virus from neuron cells, suggesting that cross-linking of E2 molecules is essential.