Fig. 1.

(A) Viruses initiate infection through the interaction of viral proteins with virus-specific receptors on host cells. Viruses enter the host cells mainly through endocytosis, virions are uncoated, viral genome is replicated, viral proteins are produced and new virions are assembled for their final spread. (B) In ADE of infection, pre-existing non-neutralizing or sub-neutralizing antibodies bind to the virus and interact with the fragment crystallizable gamma receptors (Fcγ) mainly present on the surface of myeloid cells, facilitating the internalization of the virus into host cells by endocytosis. If the virus can productively infect these cells, it replicates and spread like in (A), increasing the production of viral particles per cell or/and increasing the number of infected cells. (C) In ADE of disease, pre-existing non-neutralizing or sub-neutralizing antibodies can form immune complexes with viral particles. These immune complexes may interact with the Fcγ receptors of host myeloid cells, activating the immunoreceptor tyrosine-based activation motifs (ITAMs) of these receptors. Alternatively, immune complexes, through the activated complement components, interact with the complement receptors of host cells, activating the complement cascade. In both cases, the activation results in the release of pro-inflammatory cytokines and chemokines and recruitment of immune cells, exacerbating the immune response.