STRUCTURE OF INFLUENZA-VIRUS HEMAGGLUTININ COMPLEXED WITH A NEUTRALIZING ANTIBODY

HAEMAGGLUTININ (HA) is the influenza surface glycoprotein that interac ts with infectivity-neutralizing antibodies. As a consequence of this immune pressure it is the variable virus component, which is important in antigenic drift, that results in recurrent epidemics of influenza. We have determined the crystallographic structure of a complex formed between the antigen-binding fragment (Fab) of a neutralizing antibody tend the membrane-distal domain ((HA top') of a HA subunit prepared f rom HA in its membrane-fusion-active conformation. A dramatic change i s seen in the structure of the Fab-combining site on complex formation . Our results indicate that neutralization of infectivity by this anti body involves the inhibition of receptor binding, and demonstrate how influenza virus can maintain its conserved receptor-binding site despi te the immune selective pressure for change in this region of the mole cule; they also contribute to a complete description of the endosomal pH-induced fusion-active HA structure.