Multiple amino acid substitutions in hemagglutinin are necessary for wild-type measles virus to acquire the ability to use receptor CD46 efficiently.
Measles virus (MV) possesses two envelope glycoproteins, namely, the receptor-binding hemagglutinin (H) and fusion proteins. Wild-type MV strains isolated in B-lymphoid cell lines use signaling lymphocyte activation molecule (SLAM), but not CD46, as a cellular receptor, whereas MV vaccine strains of the Edmonston lineage use both SLAM and CD46 as receptors. Studies have shown that the residue at position 481 of the H protein is critical in determining the use of CD46 as a receptor. However, the wild-type IC-B strain with a single N481Y substitution in the H protein utilizes CD46 rather inefficiently. In this study, a number of chimeric and mutant H proteins, and recombinant viruses harboring them, were generated to determine which residues of the Edmonston H protein are responsible for its efficient use of CD46. Our results show that three substitutions (N390I and E492G plus N416D or T446S), in addition to N481Y, are necessary for the IC-B H protein to use CD46 efficiently as a receptor. The N390I, N416D, and T446S substitutions are present in the H proteins of all strains of the Edmonston lineage, whereas the E492G substitution is found only in the H protein of the Edmonston tag strain generated from cDNAs. The T484N substitution, found in some of the Edmonston-lineage strains, resulted in a similar effect on the use of CD46 to that caused by the E492G substitution. Thus, multiple residues in the H protein that have not previously been implicated have important roles in the interaction with CD46.
Tahara
Maino
M
Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Takeda
Makoto
M
Seki
Fumio
F
Hashiguchi
Takao
T
Yanagi
Yusuke
Y
D019943:Amino Acid Substitution; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D006367:HeLa Cells; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008459:Measles virus / Q000378:metabolism*; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011991:Receptors, Virus / Q000378:metabolism*; D011995:Recombination, Genetic; D014709:Vero Cells
D006389:Hemagglutinins, Viral; D051916:Membrane Cofactor Protein; D011991:Receptors, Virus