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.

Journal of Virology
|September 2, 2011
PubMed

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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