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Updated: May 29, 2026

Method for Measurement of Viral Fusion Kinetics at the Single Particle Level
Published on: September 7, 2009
A fusion-loop antibody enhances the infectious properties of immature flavivirus particles
Izabela A Rodenhuis-Zybert1, Bastiaan Moesker, Júlia M da Silva Voorham
1Department of Medical Microbiology, Molecular Virology Section (HPC EB88), University Medical Center Groningen and University of Groningen, P.O. Box 30.001, 9700 RB Groningen, Netherlands.
Abstract:
Flavivirus-infected cells secrete a mixture of mature, partially immature, and fully immature particles into the extracellular space. Although mature virions are highly infectious, prM-containing fully immature virions are noninfectious largely because the prM protein inhibits the cell attachment and fusogenic properties of the virus. If, however, cell attachment and entry are facilitated by anti-prM antibodies, immature flavivirus becomes infectious after efficient processing of the prM protein by the endosomal protease furin. A recent study demonstrated that E53, a cross-reactive monoclonal antibody (MAb) that engages the highly conserved fusion-loop peptide within the flavivirus envelope glycoprotein, preferentially binds to immature flavivirus particles. We investigated here the infectious potential of fully immature West Nile virus (WNV) and dengue virus (DENV) particles opsonized with E53 MAb and observed that, like anti-prM antibodies, this anti-E antibody also has the capacity to render fully immature flaviviruses infectious. E53-mediated enhancement of both immature WNV and DENV depended on efficient cell entry and the enzymatic activity of the endosomal furin. Furthermore, we also observed that E53-opsonized immature DENV particles but not WNV particles required a more acidic pH for efficient cleavage of prM by furin, adding greater complexity to the dynamics of antibody-mediated infection of immature flavivirus virions.
Insights
Antibodies targeting immature flaviviruses, like West Nile virus and dengue virus, can unexpectedly make them infectious. This process relies on cell entry and furin protease activity, with some viruses needing more acidic conditions for activation.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Flaviviruses exist as mature, partially immature, and fully immature particles.
- Immature flaviviruses are noninfectious due to the prM protein inhibiting attachment and fusion.
- Anti-prM antibodies can facilitate entry and subsequent furin-mediated prM processing, rendering immature virions infectious.
Purpose of the Study:
- To investigate the infectious potential of fully immature West Nile virus (WNV) and dengue virus (DENV) particles opsonized with the E53 monoclonal antibody (MAb).
- To determine if E53, an antibody targeting the fusion-loop peptide, can confer infectivity to immature flaviviruses.
- To explore the role of cell entry and endosomal furin activity in E53-mediated flavivirus infection.
Main Methods:
- Opsonization of immature WNV and DENV particles with E53 MAb.
- Assessment of infectivity following antibody opsonization.
- Investigation of the dependence on cell entry and endosomal furin activity.
- pH-dependent analysis of prM cleavage by furin.
Main Results:
- E53 MAb opsonization rendered fully immature WNV and DENV infectious, similar to anti-prM antibodies.
- E53-mediated enhancement of infectivity required efficient cell entry and endosomal furin enzymatic activity.
- E53-opsonized immature DENV, but not WNV, required a more acidic pH for efficient prM cleavage by furin.
Conclusions:
- Antibodies targeting conserved epitopes on immature flaviviruses can induce infectivity.
- The mechanism involves antibody-facilitated entry and subsequent furin-mediated processing of the prM protein.
- Virus-specific differences in pH requirements for furin cleavage highlight the complexity of antibody-mediated flavivirus infection dynamics.
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