Human FcγRII cytoplasmic domains differentially influence antibody-mediated dengue virus infection.
J Immunol
; 190(11): 5659-65, 2013 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-23616574
ABSTRACT
Ab-dependent enhancement (ADE) of dengue virus (DENV) infection is mediated through the interaction of viral immune complexes with FcγRs, with notable efficiency of FcγRII. Most human dengue target cells coexpress activating (FcγRIIa) and inhibitory (FcγRIIb) isoforms, but their relative roles in ADE are not well understood. We studied the effects of FcγRIIa and FcγRIIb by transfecting cells to express each individual receptor isoform or through coexpression of both isoforms. We showed that although both isoforms similarly bind dengue-immune complexes, FcγRIIa efficiently internalized virus leading to productive cellular infection, unlike FcγRIIb. We next focused on the main discriminating feature of these isoforms their distinct intracytoplasmic tails (FcγRIIa with an immunoreceptor tyrosine-based activation motif [ITAM] and FcγRIIb with an immunoreceptor tyrosine-based inhibitory motif [ITIM]). We engineered cells to express "swapped" versions of their FcγRII by switching the cytoplasmic tails containing the ITAM/ITIM motifs, leaving the remainder of the receptor intact. Our data show that both FcγRIIa and FcγRIIb comparably bind dengue immune complexes. However, wild type FcγRIIa facilitates DENV entry by virtue of the ITAM motif, whereas the swapped version FcγRIIa-ITIM significantly inhibited ADE. Similarly, replacing the inhibitory motif in FcγRIIb with an ITAM (FcγRIIb-ITAM) reconstituted ADE capacity to levels of the wild type activating counterpart, FcγRIIa. Our data suggest that FcγRIIa and FcγRIIb isoforms, as the most abundantly distributed class II Fcγ receptors, differentially influence Ab-mediated DENV infection under ADE conditions both at the level of cellular infection and viral production.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de IgG
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Dengue
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Vírus da Dengue
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Domínios e Motivos de Interação entre Proteínas
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Anticorpos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article