Influence of the human high-affinity IgG receptor FcγRI (CD64) on residual infectivity of neutralized dengue virus

Abstract

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, FcγRI. 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 FcγRI- 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 γ 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 FcγRI-bearing COS cells than in controls. Compatible with the IgG subclass specificity of FcγRI, this difference was abrogated quantitatively by treatment of FcγRI-transfected cells with human IgG1 but not IgG2 myeloma protein. The magnitude of receptor-mediated plaque formation after cotransfection with γ chain was also significantly higher than in controls but was less than that observed with FcγRI transfection only, a difference probably explained by reduced levels of FcγRI expression in γ chain cotransfectants. Deletion of the FcγRI cytoplasmic domain had no effect on receptor-mediated immune complex infectivity. We conclude that the FcγRI extracellular domain is sufficient for internalization of infectious dengue virus immune complexes through a mechanism that does not involve classical ITAM-dependent signaling.