A novel amino acid position in hemagglutinin glycoprotein of measles virus is responsible for hemadsorption and CD46 binding.
Three recent isolates of measles virus Fu, IMA, and SMD obtained by using B95a cells did not exhibit hemadsorption with African green monkey red blood cells (AGM-RBC). After long-term passage in Vero cells, these Vero cell-adapted strains derived from three isolates obtained the activity to agglutinate AGM-RBC. The primary sequences of the hemagglutinin (H protein) and fusion glycoproteins (F protein) from these two types of viruses were compared and revealed that several important amino acid residues in the H protein do not converge. After adaptation, Fu strain has an Asn to Tyr substitution at position 481 and IMA strain has two substitutions--an Asp to Asn at position 14 and a Ser to Gly at position 546, SMD strain also has a Ser to Gly substitution at position 546. Since the sequences of the F protein were identical between both types of viruses, the hemadsorption alteration from negative to positive might be the result of these substitutions. Site-directed mutagenesis of the H genes were performed to confirm that the substitution of Ser --> Gly at position 546 and Asn --> Tyr at position 481 in the H protein were responsible for hemadsorption alteration. Anti-CD46 monoclonal antibody (M75 and M160) study made clear that these two substitutions also governed the MV H protein's interaction with CD46 receptor. Our results showed that two important amino acid residues in MV H protein govern the binding to CD46 receptor and hemadsorption. In this paper, we reported a novel amino acid residue at position 546 in MV H protein, which was critical for hemadsorption and CD46 binding.
Li
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L
Institute of Virology, Wuhan University, China.
Qi
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Y
D019943:Amino Acid Substitution; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006382:Hemadsorption / Q000235:genetics; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008457:Measles / Q000821:virology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018103:Morbillivirus / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; C497857:CD46 protein, human; C104413:H protein, Dolphin morbillivirus; D006389:Hemagglutinins, Viral; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D014760:Viral Fusion Proteins