Beside antibody-mediated cellular cytotoxicity (ADCC),the binding ofmAbs to pathogens or infected cells is thought to induce complement (C) activation which should result in the destruction of pathogens or infected cells by C-dependent cellular cytotoxicity (CDCC) and C-mediated lysis (CML).However the C-mediated effector functions are limited,as pathogens or infected cells are protected from C-induced damage by regulators of C activation (RCAs),similar as observed for normal cells.Among these RCAs are proteins in fluid phase,like factor H (fH).Therefore,blocking of the fH binding may render the pathogens or infected cells increasingly susceptible to CML.Our first in vitro results provided evidence that an approach based on blocking fH binding to HIV is successful and overcomes the resistance of the virus against the lytic attacks of the complement system.Having identified similar protection mechanisms at murine retroviruses,we have now access to an in vivo model to show that complement-based constructs may become a valuable tool for reducing the viral titer and controlling retroviral infections in mice.