Immunoglobulin G antibody-mediated enhancement of measles virus infection can bypass the protective antiviral immune response

Ianko D. Iankov, Manoj Pandey, Mary Harvey, Guy E. Griesmann, Mark J Federspiel, Stephen J Russell

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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 γ receptor (FcγR)-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 FcγR-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.

Original languageEnglish (US)
Pages (from-to)8530-8540
Number of pages11
JournalJournal of Virology
Volume80
Issue number17
DOIs
StatePublished - Sep 2006

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Measles virus
immunoglobulin G
Virus Diseases
Antiviral Agents
Immunoglobulin G
immune response
antibodies
Antibodies
infection
macrophages
Fc Receptors
Macrophages
mice
Measles
monocytes
receptors
glycoproteins
Monocytes
monoclonal antibodies
complement

ASJC Scopus subject areas

  • Immunology

Cite this

Immunoglobulin G antibody-mediated enhancement of measles virus infection can bypass the protective antiviral immune response. / Iankov, Ianko D.; Pandey, Manoj; Harvey, Mary; Griesmann, Guy E.; Federspiel, Mark J; Russell, Stephen J.

In: Journal of Virology, Vol. 80, No. 17, 09.2006, p. 8530-8540.

Research output: Contribution to journalArticle

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