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Updated: May 18, 2026
Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
Published on: September 14, 2014
Inhibition of Marburg virus budding by nonneutralizing antibodies to the envelope glycoprotein
Masahiro Kajihara1, Andrea Marzi, Eri Nakayama
1Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.
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.
Insights
Marburg virus (MARV) envelope glycoprotein (GP)-specific antibodies inhibit virus release by preventing particle budding. This reveals a new mechanism for antibody-mediated protection against MARV infection.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- The Marburg virus (MARV) envelope glycoprotein (GP) is crucial for host cell entry and is a primary target for neutralizing antibodies.
- While Ebola virus (EBOV) neutralization mechanisms are increasingly understood, MARV infectivity regulation by antibodies remains less clear.
Purpose of the Study:
- To investigate the mechanism by which MARV GP-specific antibodies regulate MARV infectivity.
- To identify novel antibody-mediated inhibition strategies against MARV.
Main Methods:
- Utilized MARV GP-specific monoclonal antibodies (AGP127-8 and MGP72-17) and their Fab fragments.
- Assessed antibody effects on MARV entry, virus budding, and the formation of virus-like particles (VLPs).
- Performed morphological analyses of VLP-producing cells in the presence of antibodies.
Main Results:
- MARV GP-specific antibodies AGP127-8 (IgG1) and MGP72-17 (IgM) significantly reduced progeny virus release without inhibiting cell entry.
- These antibodies inhibited the formation of MARV VLPs, an effect not observed with the AGP127-8 Fab fragment.
- Morphological studies showed antibodies caused VLPs to aggregate on the surface of infected cells, arresting budding.
Conclusions:
- Demonstrated a novel antibody-mediated mechanism inhibiting MARV budding by arresting nascent virus particles on the cell surface.
- Suggests that antibodies targeting MARV GP can contribute to protective immunity through mechanisms beyond classical neutralization.
- Highlights that classical neutralizing activity is not the sole determinant of protective MARV antibodies for prophylactic and therapeutic applications.
