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 intracellularly, defective in binding to cellular receptors or defective for acylation within the cytoplasmic C terminus have been generated. Here, the properties of these mutated HA molecules are described and their incorporation into the lipid membrane of released human immunodeficiency virus (HIV)-like particles is analysed. It is demonstrated that, when produced from cells coexpressing any of the binding-competent Aichi-HA molecules, release of HIV-like particles into the extracellular medium is reduced and the particles that are released fail to incorporate Aichi-HA. These blocks in release and incorporation, respectively, can both be overcome. The release of normal amounts of particles with incorporated HA can be achieved either by mutation of the receptor-binding site on the Aichi-HA molecule or by removal of sialic acid from surface proteins with neuraminidase. In contrast, as a result of blockage of the sialic acid-binding site by sialidated oligosaccharides on the HA itself, the HA of influenza virus A/FPV/Rostock/34 (H7N1) is efficiently incorporated into HIV-like particles. These results, namely that particle release can be inhibited by interactions between the incorporated glycoprotein and the cell surface and/or that interactions with other cellular components can be inhibitory to incorporation into retrovirus envelopes, probably reflect general principles that may hold for many viral and cellular glycoproteins.
Bosch
Valerie
V
Forschungsschwerpunkt Angewandte Tumorvirologie, F0200, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany1.
Kramer
Beatrice
B
Forschungsschwerpunkt Angewandte Tumorvirologie, F0200, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany1.
Pfeiffer
Tanya
T
Forschungsschwerpunkt Angewandte Tumorvirologie, F0200, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany1.
Stärck
Lilian
L
Forschungsschwerpunkt Angewandte Tumorvirologie, F0200, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany1.
Steinhauer
David A
DA
Division of Virology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK2.
D000818:Animals; D006678:HIV / Q000502:physiology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000502:physiology*; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009439:Neuraminidase / Q000494:pharmacology; D011991:Receptors, Virus / Q000502:physiology*; D014771:Virion / Q000502:physiology*
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid