Influence of the human high-affinity IgG receptor FcgammaRI (CD64) on residual infectivity of neutralized dengue virus.
We examined dengue virus immune complex-phagocyte interaction with respect to a single Fc receptor class using a transient expression system involving the high-affinity human macrophage receptor, FcgammaRI. We found that New Guinea C strain dengue 2 virus formed well-defined plaques in normal and transfected COS cells and we analyzed the structural determinants of FcgammaRI-mediated binding and internalization of dengue 2 virus immune complexes by expressing native or truncated forms of the receptor in COS cells, alone or with its accessory gamma chain signaling unit, which bears an immunoreceptor tyrosine-based activation motif (ITAM). The residual infectivity of dengue 2 virus treated with neutralizing human antiserum was strikingly higher in FcgammaRI-bearing COS cells than in controls. Compatible with the IgG subclass specificity of FcgammaRI, this difference was abrogated quantitatively by treatment of FcgammaRI-transfected cells with human IgG1 but not IgG2 myeloma protein. The magnitude of receptor-mediated plaque formation after cotransfection with gamma chain was also significantly higher than in controls but was less than that observed with FcgammaRI transfection only, a difference probably explained by reduced levels of FcgammaRI expression in gamma chain cotransfectants. Deletion of the FcgammaRI cytoplasmic domain had no effect on receptor-mediated immune complex infectivity. We conclude that the FcgammaRI extracellular domain is sufficient for internalization of infectious dengue virus immune complexes through a mechanism that does not involve classical ITAM-dependent signaling.
Department of Medicine, The Rochester General Hospital and University of Rochester School of Medicine and Dentistry, Rochester, New York, 14621-3001, USA.
J J
JJ
Schlesinger
S E
SE
Chapman
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D019556:COS Cells; D003716:Dengue Virus / Q000472:pathogenicity*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009194:Myeloma Proteins / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases; D017452:Receptors, IgG / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship; D014162:Transfection
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D009194:Myeloma Proteins; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases