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A Fusion-Loop Antibody Enhances the Infectious Properties of Immature Flavivirus Particles
- Source :
- Journal of Virology, 85(22), 11800-11808. American Society for Microbiology
- Publication Year :
- 2011
-
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.
- Subjects :
- STRUCTURAL BASIS
medicine.drug_class
viruses
Immunology
Dengue virus
Antibodies, Viral
medicine.disease_cause
Monoclonal antibody
WEST-NILE-VIRUS
Microbiology
Virus
MATURATION
Cell Line
Viral Envelope Proteins
Cricetinae
Virology
PROTEIN PRM
medicine
Animals
Antibody-dependent enhancement
CRYSTAL-STRUCTURE
Furin
DENGUE VIRUS
chemistry.chemical_classification
biology
CLEAVAGE
Antibodies, Monoclonal
virus diseases
Hydrogen-Ion Concentration
Virus Internalization
biochemical phenomena, metabolism, and nutrition
BORNE ENCEPHALITIS-VIRUS
ENVELOPE GLYCOPROTEIN
biology.organism_classification
Antibody-Dependent Enhancement
Flavivirus
chemistry
Insect Science
biology.protein
Pathogenesis and Immunity
Antibody
Glycoprotein
MEDIATED NEUTRALIZATION
West Nile virus
Subjects
Details
- Language :
- English
- ISSN :
- 0022538X
- Volume :
- 85
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....78b42d48d08472550766dd548be7d3e6