Mechanisms of antibody-dependent enhancement and its research progress in animal coronaviruses

Figures

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  Figure 1. Fc receptor-mediated ADE. Antibody-opsonized virions bind FcγRs and are internalized through endocytic or phagocytic pathways. Under non-enhancing conditions, internalized particles are delivered to lysosomes for degradation and antigen presentation. During ADE, some viruses avoid rapid degradation, escape from endosomal compartments, or exploit FcγR-associated signaling, thereby promoting productive infection or immune modulation.

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  Figure 2. Complement receptor-mediated ADE. Antibody-virus complexes may recruit complement components and become decorated with C3 fragments, allowing interaction with complement receptors and enhanced uptake. Alternatively, C1q may bridge immune complexes to C1q receptors and increase viral attachment independently of downstream complement activation.

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  Figure 3. Antibody-dependent conformational changes in viral proteins. (i) Antibody-dependent conformational changes in SARS-CoV-1/2 spike protein: Infection-enhancing antibodies targeting the N-terminal domain (NTD) of the SARS-CoV-1/2 spike protein bind to a specific enhancing epitope within the NTD, thereby inducing an open conformation of the RBD. This conformational shift enhances the binding affinity between the spike protein and the host cell receptor ACE2, potentiating viral entry. (ii) Antibody-dependent conformational changes in MERS-CoV spike protein: The enhancing antibody Mersmab1 binds to the receptor-binding motif within the RBD of the MERS-CoV spike protein, stabilizing the RBD in an upright orientation. This stabilization triggers conformational rearrangements in the spike trimer, exposing the S2′ protease cleavage site. Notably, Mersmab1-dependent and DPP4-dependent MERS-CoV entry share a common downstream pathway, with the antibody effectively mimicking the native receptor to facilitate viral fusion and internalization.

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  Figure 4. Antibody-dependent immune evasion. During ADE, immune-complex uptake can suppress antiviral innate signaling. In DENV models, ADE impairs TLR/RLR/JAK-STAT-associated pathways and reduces IFN-related responses. In RRV infection, ADE suppresses STAT1, NF-κB, and antiviral gene expression. In SARS-CoV-2 infection, anti-IFN autoantibodies provide a distinct example of antibody-dependent suppression of antiviral cytokine activity.

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  Figure 5. Antibody-dependent enhancement of inflammation. During ADEI, immune complexes amplify inflammatory responses through FcγR-PRR crosstalk, inflammasome signaling, and cytokine release. These pathways can promote NF-κB activation, NLRP3 inflammasome maturation, JAK-STAT-mediated cytokine amplification, pyroptosis, and tissue injury without necessarily increasing pathogen burden.