title: Fusion of influenza virus with the endosomal membrane is inhibited by monoclonal antibodies to defined epitopes on the hemagglutinin.
abstract: Epitopes on the hemagglutinin (HA) of A/seal/Massachusetts/1/80 (H7N7) influenza virus were mapped by genetic analysis of variants selected with monoclonal antibodies (MAbs). Electron microscopic studies demonstrated that the sites and the directions to which hemagglutination-inhibiting (HI) MAbs and non-HI MAbs bound were different on the HA molecule. Morphological analysis revealed that HI MAbs blocked attachment of the virus to the cells, while non-HI MAbs did not. Virus particles bound with non-HI MAbs were then found in the intracellular vacuoles. Together with the electron microscopic findings, a fluorescence dequenching assay indicated that non-HI MAbs inhibited the fusion of virus with the intracellular vacuolar membrane. It was thus shown that non-HI neutralizing MAbs did not inhibit attachment of the virus to the host cell receptor, but inhibited the fusion step in intracellular vacuoles. The results support the hypothesis that anti-HA MAbs which lack HI activity neutralize viral infectivity by interfering with the low pH-induced conformational change in the HA molecule, resulting in inhibition of the fusion step in the viral replication process (Kida, H., Yoden, S., Kuwabara, M., Yanagawa, R., 1985. Interference with a conformational change in the HA molecule of influenza virus by antibodies as a possible neutralization mechanism. Vaccine 3, 219-222).
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Imai
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
authors.forename: K
authors.initials: K
authors.lastname: Okazaki
authors.forename: H
authors.initials: H
authors.lastname: Kida
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002642:Chick Embryo; D004285:Dogs; D011992:Endosomes / Q000378:metabolism*; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D004912:Erythrocytes / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology* / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008561:Membrane Fusion; D051379:Mice; D008807:Mice, Inbred BALB C; D046048:Seals, Earless / Q000821:virology; D014617:Vacuoles / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus