Enhancing antibodies, macrophages and virulence in mouse cytomegalovirus infection

The infectivity of tissue culture-passed mouse cytomegalovirus (MCMV) for resident mouse peritoneal macrophages in the presence of serial dilutions of antiviral antibody was studied by fluorescent antibody staining and virus yields. Although MCMV was neutralized by high concentrations of antiserum, there was a twofold enhancement of infectivity by subneutralizing antibody concentrations. On further dilution of antiserum, significant neutralization appeared again. When F(ab')2 fragments of anti-MCMV IgG were used or when macrophages were pretreated with monoclonal antibody to Fc receptor, there was no enhancement, and no neutralization at high dilutions of antiserum. This suggests that both enhancement and high dilution neutralization are mediated via the Fc portion of IgG and Fc receptors of macrophages. Tissue culture-passed virus whose infectivity for macrophages was reduced by high dilutions of antibody was converted to a more infectious state by addition of anti-mouse immunoglobulin. Similar results were obtained with salivary gland virus, which is less infectious for macrophages and is coated with non-neutralizing antibody. Tissue culture-passed virus is known to be less virulent for suckling mice and more infectious for macrophages than salivary gland-passed virus. When tissue culture-passed virus was coated with appropriately diluted antiviral antibody, not only was its infectivity for macrophages reduced, but it also became more virulent than control virus treated with normal mouse serum. These results are interpreted in terms of the optimal density of Fc on the virus-immunoglobulin complex in relation to the density of Fc receptors on macrophages.