Neutralization of Type A Influenza virus by Immunoglobulins M, A and G: A Summary

Abstract

Influenza virus provides a good system for study of the neutralization of enveloped viruses since the structure of major neutralization antigen, the haemagglutin in (HA), is known at the 2.8 Å level and there are many mabs, the epitopes of which have been located on the HA by escape-mutant mapping (Wilson et al. 1981; Wiley et al. 1981; Wilson and Cox 1990). The following discussion is confined to the HA and its antibodies. The NA is covered in Sect. 16. The HA consists of two disulphide-linked polypeptides which are formed by protease cleavage from a single precursor: the transmembrane HA2, which is not involved in neutralization and in the virion is unable to react with antibody (Becht et al. 1984), and the distal HA1. The HA is a homotrimer with the original C terminus inside the virion. There are five potential neutralization sites per monomer (A–E on H3), although D is partly formed by the adjacent interfaces of the monomer. All are located on the globular head formed by HA1 (Fig. 1). There are fourteen subtypes of type A HA (H1–H14; Kawaoka et al. 1990) and the crystal structure of H3 only is known. How closely the arrangement of antigenic sites is conserved between subtypes is uncertain but there are significant differences between H3 and H1 (Caton et al. 1982). Strict division into five antigenic sites is not always possible (Brown et al. 1990) and some would prefer to regard HA1 as an antigenic continuum. All epitopes are discontinuous and few antipeptide sera have neutralizing activity even though they can react to very high titre by enzyme-linked immunosorbent assay (ELISA). Each HA monomer has an attachment site (i.e. three per trimer) for terminally linked N-acetyl neuraminic (sialic) acid; this site is not immunogenic and no antibodies are made against it. According to estimates with different strains, type A influenza has between 400 and 1000 HA trimers per virion, roughly 10 times more than HIV-1 (Sect. 25).