title: Neutralization capacity of measles virus H protein specific IgG determines the balance between antibody-enhanced infectivity and protection in microglial cells.
abstract: Neutralizing antibodies directed against measles virus (MV) surface glycoproteins prevent viral attachment and entry through the natural receptors. H protein specific IgG can enhance MV infectivity in macrophages via Fcγ receptor (FcγR)-dependent mechanism. H-specific IgM, anti-F antibodies and complement cascade activation are protective against antibody-mediated enhancement of MV infection. However, protective role of anti-H IgG against antibody-enhanced infection is not well understood. Here we designed a set of experiments to test the protective effect of H-specific IgG against FcγR-mediated infection in microglial cells. Microglial cells are also potential target of the antibody-mediated enhancement and spread of MV infection in the central nervous system. A partially neutralizing IgG monoclonal antibody (MAb) CL55, specific for MV H protein, at 10 μg/ml enhanced MV infection in mouse microglial cells by 13-14-fold. Infection-enhancing antibody concentrations induced large multinucleated syncytia formation 48-72 h post-inoculation. We generated anti-H IgG MAb 20H6 with a strong neutralization capacity >1:80,000 at 1mg/ml concentration in MV plaque-reduction neutralization assay. In contrast to the partially protective MAb CL55, enhancement of MV infectivity by MAb 20H6 required dilutions below the 1:120 serum titer considered protective against measles infection in humans. At a concentration of 10 μg/ml MAb 20H6 exhibited a dominant protective effect and prevented MAb CL55-mediated enhancement of MV infection and virus-mediated fusion. These results indicate that neutralization capacity of the H-specific IgG determines the balance between antibody enhancement and protection against MV infection in microglial cells.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA. Iankov.Ianko@mayo.edu
authors.forename: Ianko D
authors.initials: ID
authors.lastname: Iankov
authors.forename: Alan R
authors.initials: AR
authors.lastname: Penheiter
authors.forename: Guy E
authors.initials: GE
authors.lastname: Griesmann
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Carlson
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Federspiel
authors.forename: Evanthia
authors.initials: E
authors.lastname: Galanis
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D006801:Humans; D008459:Measles virus / Q000276:immunology* / Q000472:pathogenicity*; D051379:Mice; D009457:Neuroglia / Q000821:virology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014764:Viral Proteins