Immunoglobulin g antibody-mediated enhancement of measles virus infection can bypass the protective antiviral immune response.
Antibodies to viral surface glycoproteins play a crucial role in immunity to measles by blocking both virus attachment and subsequent fusion with the host cell membrane. Here, we demonstrate that certain immunoglobulin G (IgG) antibodies can also enhance the entry of measles virus (MV) into monocytes and macrophages. Antibody-dependent enhancement of infectivity was observed in mouse and human macrophages using virions opsonized by a murine monoclonal antibody against the MV hemagglutinin (H) glycoprotein, polyclonal mouse anti-MV IgG, or diluted measles-immune human sera. Neither H-specific Fab fragments nor H-specific IgM could enhance MV entry in monocytes or macrophages, indicating involvement of a Fc gamma receptor (FcgammaR)-mediated mechanism. Preincubation with an anti-fusion protein (anti-F) monoclonal antibody or a fusion-inhibitory peptide blocked infection, indicating that a functional F protein was required for viral internalization. Classical complement pathway activation did not promote infection through complement receptors and inhibited anti-H IgG-mediated enhancement. In vivo, antibody-enhanced infection allowed MV to overcome a highly protective systemic immune response in preimmunized IfnarKo-Ge46 transgenic mice. These data demonstrate a previously unidentified mechanism that may contribute to morbillivirus pathogenesis where H-specific IgG antibodies promote the spread of MV infection among FcgammaR-expressing host cells. The findings point to a new model for the pathogenesis of atypical MV infection observed after immunization with formalin-inactivated MV vaccine and underscore the importance of the anti-F response after vaccination.
Iankov
Ianko D
ID
Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905, USA. Iankov.Ianko@mayo.edu
Pandey
Manoj
M
Harvey
Mary
M
Griesmann
Guy E
GE
Federspiel
Mark J
MJ
Russell
Stephen J
SJ
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D006389:Hemagglutinins, Viral / Q000276:immunology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D008264:Macrophages / Q000821:virology; D008457:Measles / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control / Q000821:virology; D008458:Measles Vaccine / Q000008:administration & dosage / Q000276:immunology; D008459:Measles virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000821:virology; D020298:U937 Cells / Q000821:virology; D014760:Viral Fusion Proteins / Q000276:immunology
D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007074:Immunoglobulin G; D008458:Measles Vaccine; D014760:Viral Fusion Proteins