Abstract
Antibodies play a crucial role in host defense against viruses, both by preventing infection and by controlling viral replication. Besides their capacity to neutralize viruses, antibodies also exert their antiviral effects by crystallizable fragment (Fc)-mediated effector mechanisms. This involves a bridge between innate and adaptive immune systems, wherein antibodies form immune complexes that drive numerous innate immune effector functions, including antibody-dependent cellular cytotoxicity, antibody-dependent complement-mediated lysis, and antibody-dependent phagocytosis. Here, we review certain mechanisms that modulate these antibody-mediated effector functions against virally infected cells, such as viral glycoprotein shedding, viral glycoprotein internalization, antibody cooperativity, and antibody glycosylation. These mechanisms can either protect viral replication or enhance infected cell clearance. Here we discuss the importance of these understudied factors in modulating Fc-mediated effector functions.
Highlights
Antibodies carry out a multitude of preventative and therapeutic antiviral activities
Vaccines 2019, 7, 103 phagocytosis and stimulation of antigen-presenting cells [11,12]. These antibody-mediated effector functions have been implicated in the protection and control against many viruses, including influenza viruses [13], Ebola virus (EboV) [14,15], and the human immunodeficiency virus (HIV-1) [16]
Despite the recent surge in the study of Fc-mediated effector functions in controlling viral infections, there remain some understudied parameters. These include viral glycoprotein shedding that can redirect humoral immune responses from infected to uninfected cells, glycoprotein internalization that can modulate immune complex formation and the ability of different families of antibodies to synergize for effector cell activation, as well as antibody glycosylation. This review summarizes these mechanisms with a focus on HIV-1, while drawing parallels with other viruses
Summary
Antibodies carry out a multitude of preventative and therapeutic antiviral activities. Vaccines 2019, 7, 103 phagocytosis and stimulation of antigen-presenting cells [11,12] These antibody-mediated effector functions have been implicated in the protection and control against many viruses, including influenza viruses [13], Ebola virus (EboV) [14,15], and the human immunodeficiency virus (HIV-1) [16]. Despite the recent surge in the study of Fc-mediated effector functions in controlling viral infections, there remain some understudied parameters These include viral glycoprotein shedding that can redirect humoral immune responses from infected to uninfected cells, glycoprotein internalization that can modulate immune complex formation and the ability of different families of antibodies to synergize for effector cell activation, as well as antibody glycosylation. The consequences of these mechanisms in determining the efficacy of Fc-mediated effector responses and their implication for vaccine design and therapeutics are discussed
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