Herpesviral Fcgamma receptors: culprits attenuating antiviral IgG?
Production of IgG in response to virus infection is central to antiviral immune effector functions and a hallmark of B cell memory. Antiviral antibodies (Abs) recognising viral glycoproteins or protein antigen displayed on the surface of virions or virus-infected cells are crucial in rendering the virus noninfectious and in eliminating viruses or infected cells, either acting alone or in conjunction with complement. In many instances, passive transfer of Abs is sufficient to protect from viral infection. Herpesviruses (HV) are equipped with a large array of immunomodulatory functions which increase the efficiency of infection by dampening the antiviral immunity. Members of the alpha- and beta-subfamily of the Herpesviridae are distinct in encoding transmembrane glycoproteins which selectively bind IgG via its Fc domain. The Fc-binding proteins constitute viral Fcgamma receptors (vFcgammaRs) which are expressed on the cell surface of infected cells. Moreover, vFcgammaRs are abundantly incorporated into the envelope of virions. Despite their molecular and structural heterogeneity, the vFcgammaRs generally interfere with IgG-mediated effector functions like antibody (Ab)-dependent cellular cytolysis, complement activation and neutralisation of infectivity of virions. vFcgammaRs may thus contribute to the limited therapeutic potency of antiherpesviral IgG in clinical settings. A detailed molecular understanding of vFcgammaRs opens up the possibility to design recombinant IgG molecules resisting vFcgammaRs. Engineering IgG with a better antiviral efficiency represents a new therapeutic option against herpesviral diseases.
Budt
Matthias
M
Robert Koch-Institute, Division of Viral Infections, Nordufer 20, 13353 Berlin, Germany.
Reinhard
Henrike
H
Bigl
Arndt
A
Hengel
Hartmut
H
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D006564:Herpesviridae / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D017452:Receptors, IgG