Strategies of CMV envelope protein-mediated immune evasion. Strategies of CMV envelope protein-mediated immune evasion. (A) Strain polymorphism. Initial CMV infection elicits an antibody response that may not effectively neutralize infection by alternate strains due to variability in the CMV virion envelope proteins. (B) Epitope competition. Antibodies targeting regions of a CMV envelope protein that do not participate in critical attachment or entry processes may sterically block the binding of neutralizing antibodies to critical epitopes. (C) Fc receptor-mediated endocytosis. A CMV virion that is bound by CMV-specific antibodies may cross-link Fc receptors on the cell surface and induce endocytosis of the virion-IgG complex. Viral entry then occurs when the virus fuses with the endosomal membrane within the cell. (D) Glycan shielding. Highly glycosylated surface proteins, such as CMV gB, gO, and gN (Table 1), may prevent antibody binding by limiting access to susceptible epitopes within the glycoprotein or glycoprotein complex. (E) Cell-to-cell fusion. Surface viral envelope proteins may induce fusion between an infected cell and a bystander cell, permitting transfer of infectious material while avoiding exposure to the host neutralizing antibody response. Thomas J. Gardner, and Domenico Tortorella Microbiol. Mol. Biol. Rev. 2016; doi:10.1128/MMBR.00018-16