Immunoglobulin G Neutralization by Inhibition of Attachment of Virus to the Cell

Abstract

There are surprizingly few documented examples of immunoglobulin G (IgG) inhibiting attachment of virus to its cell receptor (Table 1). For this to occur it would seem that the IgG has to bind directly to or close by the viral attachment site or to change its conformation so that it no longer functions. Table 1 includes only data which show some indication of direct proportionality between neutralization and inhibition of attachment. For this reason some data where authors have ascribed neutralization to inhibition of attachment have been excluded, for example Venezuelan equine encephalomyelitis virus (VEEV) where there was a 90% reduction in attachment for 99.998% neutralization (Roehrig et al. 1988), poliovirus where monoclonal antibody (mab) ICJ27 caused an 80% reduction in attachment but 99% neutralization (Emini et al. 1983a) and transmissible gastroenteritis virus (TGEV) where mabs to site A of the major surface protein inhibited attachment by 78%–96% but neutralized by up to 99.999999% (Suñé et al. 1990). Another problem is that experimenters sometimes use only one concentration of IgG (e.g. Lee et al. 1981), which renders the conclusion that the observed inhibition of attachment is the primary cause of neutralization open to doubt. This is aptly illustrated by the interaction of TGEV with anti-site A mabs, where there is inhibition of attachment of already neutralized virus by a vast excess of antibody (Suñé et al. 1990). Thus much of the work cited in Table 1 should be appraised with caution. However, the study by Iorio et al. (1989) on Newcastle disease virus (NDV) pays very careful regard to the correspondance between inhibition of attachment and neutralization and shows clearly that some neutralizing mabs directed against the haemagglutinin-neuraminidase (HN) protein block attachment while others do not; the latter inhibit neither haemagglutination nor neuraminidase (NA) activity. Another group of mabs gives a degree of inhibition of attachment which is less than the observed neutralization. It is also noteworthy that attachment of rhinovirus 14 was diminished even by Fab fragments of IgG (Colonno et al. 1989) and, furthermore, this occurred with Fabs reactive with any of the four major antigenic sites.