Fusion mutants of the influenza virus hemagglutinin glycoprotein. 1985

R S Daniels, and J C Downie, and A J Hay, and M Knossow, and J J Skehel, and M L Wang, and D C Wiley

The influenza virus hemagglutinin (HA) mediates viral entry into cells by a low pH induced membrane-fusion event in endosomal vesicles. Mutant viruses with altered pH dependence for both hemolysis and the HA conformational change required for fusion were selected for their ability to grow in cells treated with amantadine hydrochloride, which raises the endosomal pH. The amino acid sequence and three-dimensional location of 19 substitutions on the HA are reported. The mutations fall into two groups, one that results in the destabilization of the pH 7.0 location of the hydrophobic N-terminal HA2 peptide, and a second that results in the alteration of intersubunit contacts, suggesting a large distortion or disruption of these contacts in the "fusion-active" conformation.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009975 Orthomyxoviridae A family of RNA viruses causing INFLUENZA and other respiratory diseases. Orthomyxoviridae includes INFLUENZAVIRUS A; INFLUENZAVIRUS B; INFLUENZAVIRUS C; INFLUENZAVIRUS D; ISAVIRUS; and THOGOTOVIRUS. Influenza Viruses,Myxoviruses,Orthomyxoviruses,Influenza Virus,Myxovirus,Orthomyxovirus
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D006389 Hemagglutinins, Viral Specific hemagglutinin subtypes encoded by VIRUSES. Viral Hemagglutinin,Viral Hemagglutinins,Hemagglutinin, Viral
D006461 Hemolysis The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. Haemolysis,Extravascular Hemolysis,Intravascular Hemolysis,Extravascular Hemolyses,Haemolyses,Hemolyses, Extravascular,Hemolyses, Intravascular,Hemolysis, Extravascular,Hemolysis, Intravascular,Intravascular Hemolyses
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000547 Amantadine An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. 1-Aminoadamantane,Adamantylamine,Adekin,Aman,Amanta,Amanta-HCI-AZU,Amanta-Sulfate-AZU,Amantadin AL,Amantadin AZU,Amantadin Stada,Amantadin-neuraxpharm,Amantadin-ratiopharm,Amantadina Juventus,Amantadina Llorente,Amantadine Hydrochloride,Amantadine Sulfate,Amixx,Cerebramed,Endantadine,Gen-Amantadine,Infecto-Flu,Infex,Mantadix,Midantan,PMS-Amantadine,Symadine,Symmetrel,Viregyt,Wiregyt,tregor,1 Aminoadamantane,AL, Amantadin,AZU, Amantadin,Amanta HCI AZU,Amanta Sulfate AZU,AmantaHCIAZU,AmantaSulfateAZU,Amantadin neuraxpharm,Amantadin ratiopharm,Amantadinneuraxpharm,Amantadinratiopharm,Gen Amantadine,GenAmantadine,Hydrochloride, Amantadine,Infecto Flu,InfectoFlu,Juventus, Amantadina,Llorente, Amantadina,PMS Amantadine,PMSAmantadine,Stada, Amantadin,Sulfate, Amantadine
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D019267 Hemagglutinin Glycoproteins, Influenza Virus Membrane glycoproteins from influenza viruses which are involved in hemagglutination, virus attachment, and envelope fusion. Fourteen distinct subtypes of HA glycoproteins and nine of NA glycoproteins have been identified from INFLUENZA A VIRUS; no subtypes have been identified for Influenza B or Influenza C viruses.

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