J.M.C. KU812 cells across multiple time points (48, 72, and 96 hours postinfection [hpi]) and a range of multiplicities of contamination (4.0??10?3 to 4 4) using various concentrations of cross-reactive dengue computer virus monoclonal antibodies (D11C and 1.6D). This antigen-specific antibody-mediated contamination was selectively coupled to chemokine ligand 5 (CCL5), interleukin 1 (IL-1), and C-X-C motif chemokine ligand 10 (CXCL10) secretion and a reduction in granzyme B (GrB) release. Therefore, mast cells and/or basophils may significantly augment Zika computer virus contamination in the context of preexisting dengue computer virus immunity. IMPORTANCE Antibodies generated against one dengue serotype can enhance contamination of another by a phenomenon called antibody-dependent enhancement (ADE). Additionally, antigenic similarities between Zika and dengue viruses can promote Zika computer virus contamination by way of ADE using these very same anti-dengue antibodies. We used the KU812 cell collection to demonstrate for the first time that anti-dengue antibodies enhanced infectious Zika computer virus replication in a mast cell model and specifically increased CCL5, CXCL10, and IL-1, while also impairing granzyme B secretion. Furthermore, enhanced Zika virus contamination and selective mediator release were mechanistically dependent on fragment crystallizable gamma receptor II (FcRII). These findings establish a new model for Zika computer virus research and a new subcategory of immune cells previously unexplored in the context of Zika computer virus enhancement while being some of the very first immune cells likely to meet a blood-feeding infected mosquito. KEYWORDS: CD32, Fc gamma RII, Zika computer virus, antibody-dependent enhancement, basophil, chemokines, cytokines, dengue computer virus, mast cell INTRODUCTION Antibody-dependent enhancement (ADE) is usually a phenomenon whereby preexisting humoral immunity to one viral contamination may augment contamination of a subsequent antigenically similar computer virus. Enhanced viral replication in an antibody-dependent mechanism was first observed with Murray Valley encephalitis computer virus (1). It was not until Halstead et al. (2) reported a similar observation with dengue computer virus (DENV) that ADE would begin to gain significant attention. DENV-enhanced contamination is a rare idiosyncrasy in which preexisting immunity to a particular DENV serotype can enhance disease severity to a heterotypic secondary DENV contamination. However, ADE is usually a controversial phenomenon in part due to challenges in studying its impact, including a historical lack of long-term epidemiological studies and, at times, improper attribution of studies to humans. It was not until large epidemiological studies in children that evidence of ADE of DENV was uncovered (3, 4). Zika computer virus (ZIKV) contamination is associated with fever, muscle mass aches, conjunctivitis, Guillain-Barr, spontaneous abortion, microcephaly, and intrauterine growth restriction (5). Considering the double-tap potential of DENV contamination, the impact of previous DENV immunity on ZIKV contamination severity gained significant attention during the 2015 Latin America ZIKV epidemic with reports of potential anti-DENV antibodies cross-reacting with ZIKV (6,C9). ZIKV and DENV are mosquito-borne that have significant evolutionarily conserved parallels (10). Amino acid similarities between DENV and ZIKV E structural proteins (7, 11) bridge the immune response where DENV antibodies have the potential to cross-react with ZIKV at nonneutralizing levels and augment ZIKV replication by ADE (8, 12,C15) and (12, 16). It was later suggested that the severity of the Latin American ZIKV epidemic was in part attributable to sero-cross-reactivity complexes that augmented ZIKV contamination in areas of endemicity (7, 8, 15, 17). However, studies have also shown cross-protection of ZIKV contamination by DENV humoral responses (7, 9, 18, 19) along Rabbit Polyclonal to E-cadherin with minimal impact on enhancement or neutralization at convalescence (20). Demanding long-term prospective epidemiological studies are needed to determine A-770041 the extent of flavivirus cross-reactivity to which rationale should be supported from and discoveries. Mast cells are sentinel leukocytes that generate expulsive physiological reactions against helminths, along with improper immune responses to innocuous substances A-770041 clinically characterized as allergies (21). Additionally, mast cells are integral in coordinating early immune defenses as they constantly surveil the connective tissue and mucosal barriers for pathogenic microorganisms (22). Characteristically situated in the periphery, cutaneous mast cells are then among the first immune cell types interfaced with an infectious mosquito at the intradermal space. Mast cell-mosquito interactions are most commonly experienced as a classical wheal A-770041 and flare reaction (i.e., A-770041 mosquito bite) as a result of mast cell-immune mediated responses to mosquito salivary proteins that aid in the blood feeding process (23). Phenotypically similar to the mast cell is the KU812 mast cell/basophil precursor (24, 25), a cell model consistently used to explore mast cell-interactions (26,C34). Additionally, this cell type has been shown to be permissive to DENV contamination in an ADE.