AN ANTIBODY WHICH BINDS TO THE MEMBRANE-PROXIMAL END OF INFLUENZA-VIRUS HEMAGGLUTININ (H3 SUBTYPE) INHIBITS THE LOW-PH-INDUCED CONFORMATIONAL CHANGE AND CELL-CELL FUSION BUT DOES NOT NEUTRALIZE VIRUS

A monoclonal antibody, LMBH6, was derived from mice which had been seq uentially immunized with bromelain-cleaved haemagglutinin (BHA) from i nfluenza virus A/Aichi/2/68, A/Victoria/3/75 and A/Philippines/2/82 (a ll H3N2). LMBH6 recognizes the haemagglutinin (HA) of all H3N2 influen za A strains tested, which were isolated between 1968 and 1989, HA in the low-pH-induced conformation is not recognized, and cleavage of the HA(0) precursor to HA(1) and HA(2) is needed to obtain efficient bind ing. Compared to other monoclonal antibodies, binding of LMBH6 to viru s and to virus-infected cells is weak, while binding to BHA is compara ble. Electron microscopy demonstrates binding to the membrane proximal end of the stem structure. The antibody shows no haemagglutination-in hibition activity, but inhibits polykaryon formation and the low-pH-in duced conformational change of BHA, However, LMBH6 cannot prevent infe ction of MDCK cells but slows the growth of virus when included in a p laque assay overlay.