Inhibition of release of lentivirus particles with incorporated human influenza virus haemagglutinin by binding to sialic acid-containing cellular receptors

Mutants of the haemagglutinin (HA) gene of human influenza virus A/Aichi/2/ 68 (H3N2) encoding HA proteins that are proteolytically cleaved intracellul arly, defective in binding to cellular receptors or defective for acylation within the cytoplasmic C terminus have been generated. Here, the propertie s of these mutated HA molecules are described and their incorporation into the lipid membrane of released human immunodeficiency virus (HIV)-like part icles is analysed. It is demonstrated that, when produced from cells coexpr essing any of the binding-competentAichi-HA molecules, release of HIV-like particles into the extracellular medium is reduced and the particles that a re released fail to incorporate Aichi-HA. These blocks in release and incor poration, respectively, can both be overcome. The release of normal amounts of particles with incorporated HA can be achieved either by mutation of th e receptor-binding site on the Aichi-HA molecule or by removal of sialic ac id from surface proteins with neuraminidase. In contrast, as a result of bl ockage of the sialic acid-binding site by sialidated oligosaccharides on th e HA itself, the HA of influenza virus A/FPV/Rostock/34 (H7N1) is efficient ly incorporated into HIV-like particles. These results, namely that particl e release can be inhibited by interactions between the incorporated glycopr otein and the cell surface and/or that interactions with other cellular com ponents can be inhibitory to incorporation into retrovirus envelopes, proba bly reflect general principles that may hold for many viral and cellular gl ycoproteins.