Antibody-dependent Enhancement - Mechanism

Mechanism

There are several possibilities to explain the phenomenon:

1. A viral surface protein laced with antibodies against a virus of one serotype binds to a similar virus with a different serotype. The binding is meant to neutralize the virus surface protein from attaching to the cell, but the antibody bound to virus also binds to the receptor of the cell, the Fc-region antibody receptor FcγR. This brings the virus into close proximity to the virus-specific receptor, and the cell internalizes the virus through the normal infection route.
2. A virus surface protein may be attached to antibodies of a different serotype, activating the classical pathway of the complement system. The complement cascade system instead binds C1Q complex attached to the virus surface protein via the antibodies, which in turn bind C1q receptor found on cells, bringing the virus and the cell close enough for a specific virus receptor to bind the virus, beginning infection.. This mechanism has not been shown specifically for DENV infection, but is supposed to occur with Ebola virus infection in vitro.
3. When an antibody to a virus is present for a different serotype, it is unable to neutralize the virus, which is then ingested into the cell as a sub-neutralized virus particle. These viruses are phagocytosed as antigen-antibody complexes, and degraded by macrophages. Upon ingestion the antibodies no longer even sub-neutralize the body due to the denaturing condition at the step for acidification of phagosome before fusion with lysosome. The virus becomes active and begins its proliferation within the cell.