In vitro, antiviral activity can be separated into activity against virions and activity against infected cells. The activity against virions most often considered is neutralization. Antibody-dependent complement-mediated virolysis (ADCMV) is also an activity directed against free virions. Antibodies can also bind to viral products on infected cells to trigger effector functions, including activation of complement and antibody-dependent cellular cytotoxicity (ADCC).
Fig.1 Multiple Fc-mediated activities of antiviral monoclonal antibodies. (Lambour, 2016)
Neutralization is the reduction and loss of virus infectivity caused by antibodies, thereby blocking a step in the viral replication cycle that precedes virally encoded transcription or synthesis. There have been multiple attempts to define the mechanisms of neutralization. These mechanisms include aggregation, inhibition of viral entry by inhibition of attachment, and inhibition of fusion with the target cell, as well as post-entry mechanisms, such as interference with primary and secondary uncoating of the genetic information of the virus.
When viruses are exposed to a source of complement, complement activation can either directly mediate the neutralization of viruses or augment antibody-dependent neutralization. Specific antibody alone can efficiently neutralize many viruses, but complement activation can enhance the antiviral effects of antibodies by opsonizing virions or inducing lysis of the particles (Fig.2C). ADCMV can directly neutralize virus particles through opsonization and membrane attack complex (MAC) formation on the virion. There has been considerable research describing ADCMV and the anti-virolytic evasion methods employed by many enveloped viruses, such as HIV.
ADCC is triggered by the binding of the Fc segment of antibodies to the Fc receptors (FcRs) on effector cells thereby inducing effector cells to release cytotoxic substances such as perforin and granzymes. Therefore, ADCC responses to viral infection are a form of antibody-regulated immune responses mediated through the Fc fragment. The ADCC activity can contribute to viral clearance through the killing and removal of infected cells.
Complement is activated by antibodies IgG and IgM through activation of the classical pathway to induce complement-dependent cytotoxicity (CDC). The complement system can directly neutralize virus particles through MAC formation on virus-infected cells or targeting intracellular viral components for proteasomal degradation.
Fig.2 Mechanisms by which antibodies mediate effector functions. (Florese, 2007)
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References
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