Soluble NS1 antagonizes IgG- and IgA-mediated monocytic phagocytosis of DENV infected cells

Dengue virus (DENV) is endemic in over 100 countries, infecting an estimated 400 million individuals every year. Infection with DENV raises a significant antibody response, primarily consisting of antibodies targeting viral (structural) proteins. However, not all DENV antigens are part of the virion itself, as the DENV genome encodes several non-structural (NS) proteins. One of these, NS1, has been shown to be antigenic and is expressed on the membrane of DENV-infected cells. IgG and IgA isotype antibodies that bind NS1 are detectable in serum following DENV infection and are also capable of interacting with Fc receptors expressed on professional phagocytes. Our study aims to determine if NS1-binding IgG and IgA isotype antibodies contribute to the clearance of DENV-infected cells by professional phagocytes through antibody mediated phagocytosis/trogocytosis. Using an in vitro model of trogocytosis we observed that both IgG and IgA isotype antibodies can facilitate facilitating monocytic uptake of DENV NS1 expressing plasma membrane in an additive fashion. This process was dependent on the expression of FcγRI (CD64) and FcαR (CD89) for IgG and IgA mediated membrane uptake, respectively. Furthermore, this process was antagonized by the presence of soluble NS1, suggesting that the production of soluble NS1 by infected cells may serve as an immunological chaff, thereby antagonizing opsonization and clearance of infected cells by NS1-specific IgG and IgA isotype antibodies.