Virus-induced complement activation and neutrophil-mediated cytotoxicity against respiratory syncytial virus (RSV)

Complement-dependent neutrophil-mediated cytotoxicity (CDNC) was determined by specific release of 51-chromium (51Cr) from respiratory syncytial virus infected HEp2 cells in a microcytotoxicity assay. There was significant release of 51Cr from RSV infected cells as compared to uninfected cells in the presence of complement (C) and neutrophils (PMN). The degree of cytotoxicity was dependent upon the concentration of C used in the assay. Such cytotoxicity was effectively abolished after heat-inactivation of complement. Complement deficient in C4 did not induce cytotoxicity. Similarly, inhibitors of C1 or C3 blocked CDNC. The maximal CDNC was observed at 37 degrees C with little or no response at 4 degrees C. Lymphocytes and monocytes mediated complement-dependent cytotoxicity very poorly in comparison to PMN. Evidence of complement activation by infected cells was demonstrated by the detection of C3 fixed to RSV infected cells by indirect immunofluorescence. Treatment of C with EDTA or heat prevented subsequent attachment of C3 to the infected cells. These in vitro observations suggest an initial activation of complement by RSV infected cells and subsequent lysis by PMN. It is proposed that this process may play a role in the elimination of virus in the early phase of infection in the absence of specific antibody or sensitized lymphocytes.