title: A fusion-loop antibody enhances the infectious properties of immature flavivirus particles.
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.
authors: Department 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.
authors: Izabela A
authors: IA
authors: Rodenhuis-Zybert
authors: Bastiaan
authors: B
authors: Moesker
authors: Júlia M
authors: JM
authors: da Silva Voorham
authors: Heidi
authors: H
authors: van der Ende-Metselaar
authors: Michael S
authors: MS
authors: Diamond
authors: Jan
authors: J
authors: Wilschut
authors: Jolanda M
authors: JM
authors: Smit
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000378:metabolism*; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D006224:Cricetinae; D003716:Dengue Virus / Q000276:immunology / Q000472:pathogenicity; D045683:Furin / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism*; D053586:Virus Internalization; D014902:West Nile virus / Q000276:immunology / Q000472:pathogenicity
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; C074932:prM protein, Flavivirus; D045683:Furin