title: Inhibition of Marburg virus budding by nonneutralizing antibodies to the envelope glycoprotein.
abstract: The envelope glycoprotein (GP) of Marburg virus (MARV) and Ebola virus (EBOV) is responsible for virus entry into host cells and is known as the only target of neutralizing antibodies. While knowledge about EBOV-neutralizing antibodies and the mechanism for the neutralization of infectivity is being accumulated gradually, little is known about antibodies that can efficiently regulate MARV infectivity. Here we show that MARV GP-specific monoclonal antibodies AGP127-8 (IgG1) and MGP72-17 (IgM), which do not inhibit the GP-mediated entry of MARV into host cells, drastically reduced the budding and release of progeny viruses from infected cells. These antibodies similarly inhibited the formation of virus-like particles (VLPs) consisting of GP, the viral matrix protein, and nucleoprotein, whereas the Fab fragment of AGP127-8 showed no inhibitory effect. Morphological analyses revealed that filamentous VLPs were bunched on the surface of VLP-producing cells cultured in the presence of the antibodies. These results demonstrate a novel mechanism of the antibody-mediated inhibition of MARV budding, in which antibodies arrest unformed virus particles on the cell surface. Our data lead to the idea that such antibodies, like classical neutralizing antibodies, contribute to protective immunity against MARV and that the "classical" neutralizing activity is not the only indicator of a protective antibody that may be available for prophylactic and therapeutic use.
authors.affiliation: Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kajihara
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzi
authors.forename: Eri
authors.initials: E
authors.lastname: Nakayama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuroda
authors.forename: Rashid
authors.initials: R
authors.lastname: Manzoor
authors.forename: Keita
authors.initials: K
authors.lastname: Matsuno
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Reiko
authors.initials: R
authors.lastname: Yoshida
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D002522:Chlorocebus aethiops; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D029024:Marburgvirus / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006023:Glycoproteins; D014759:Viral Envelope Proteins