title: Impact of viral attachment factor expression on antibody-mediated neutralization of flaviviruses.
abstract: Neutralization of flaviviruses requires engagement of the virion by antibodies with a stoichiometry that exceeds a required threshold. Factors that modulate the number of antibodies bound to an individual virion when it contacts target cells impact neutralization potency. However, the contribution of cellular factors to the potency of neutralizing antibodies has not been explored systematically. Here we investigate the relationship between expression level of a viral attachment factor on cells and the neutralizing potency of antibodies. Analysis of the attachment factor DC-SIGNR on cells in neutralization studies failed to identify a correlation between DC-SIGNR expression and antibody-mediated protection. Furthermore, neutralization potency was equivalent on a novel Jurkat cell line induced to express DC-SIGNR at varying levels. Finally, blocking virus-attachment factor interactions had no impact on neutralization activity. Altogether, our studies suggest that cellular attachment factor expression is not a significant contributor to the potency of neutralizing antibodies to flaviviruses.
authors: Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy & Infectious Diseases, NIH, Bethesda, MD 20852, USA.
authors: Christopher J
authors: CJ
authors: Obara
authors: Kimberly A
authors: KA
authors: Dowd
authors: Julie E
authors: JE
authors: Ledgerwood
authors: Theodore C
authors: TC
authors: Pierson
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D001666:Binding Sites, Antibody; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D005416:Flavivirus / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000378:metabolism*; D009500:Neutralization Tests; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000276:immunology; D053585:Virus Attachment
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins