Molecular regulatory mechanism of virus-induced cell fusion

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Virus-induced cell fusion is regulated by the interaction between virus-factors and cellular factors. Fusion regulatory protein-1(FRP-1), which is identical with CD98, plays an important role on regulation of virus-induced cell fusion. FRP-1 is a multi-functional molecule, that is, FRP-1 can enhance and suppress virus-induced cell fusion. We constructed FRP-1 transgenic mice and knockout mice. FRP-1 knockout mice were found to be lethal, indicating FRP-1 that FRP-1 is essential and indispensable to ontogeny. In this study, we clarified that ADAM9 and CD147 molecules co-operated with FRP-1 in regulation of virus-induced cell fusion and monocytes fusion. ADAM9 is scarcely expressed on the blood monocytes, and expression of ADAM9 is induced by treatment of monocytes with anti-FRP-1 monoclonal antibody. An anti-ADAM9 antibody enhanced FRP-1-mediated cell aggregation, while it blocked FRP-1-mediated cell fusion. New protein synthesis is necessary for the expression of ADAM9 and genistein suppresses induction of ADAM9. One antibody to CD147 enhanced, white another one suppressed HIV-mediated cell fusion. Furthermore, we analyzed function of FRP-1 light chain, and discovered the N-light chains, which show high homology to FRP-1 light chain. We determined the cell and tissue distribution of the light chains and N-light chains. In this study, we established new method regulating virus induced cell fusion.