A Fusion-Loop Antibody Enhances the Infectious Properties of Immature Flavivirus Particles

Izabela A. Rodenhuis-Zybert, Bastiaan Moesker, Julia M. da Silva Voorham, Heidi van der Ende-Metselaar, Michael S. Diamond, Jan Wilschut, Jolanda M. Smit*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

58 Citaten (Scopus)


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.

Originele taal-2English
Pagina's (van-tot)11800-11808
Aantal pagina's9
TijdschriftJournal of Virology
Nummer van het tijdschrift22
Vroegere onlinedatum31-aug.-2011
StatusPublished - nov.-2011

Citeer dit