Efficiency of measles virus entry and dissemination through different receptors.
The efficiency with which different measles virus (MV) strains enter cells through the immune cell-specific protein SLAM (CD150) or other receptors, including the ubiquitous protein CD46, may influence their pathogenicity. We compared the cell entry efficiency of recombinant MV differing only in their attachment protein hemagglutinin (H). We constructed these viruses with an additional gene expressing an autofluorescent reporter protein to allow direct detection of every infected cell. A virus with a wild-type H protein entered cells through SLAM two to three times more efficiently than a virus with the H protein of the attenuated strain Edmonston, whereas cell entry efficiency through CD46 was lower. However, these subtle differences were amplified at the cell fusion stage because the wild-type H protein failed to fuse CD46-expressing cells. We also proved formally that a mutation in H protein residue 481 (asparagine to tyrosine) results in improved CD46-specific entry. To define the selective pressure exerted on that codon, we monitored its evolution in different H protein backgrounds and found that several passages in CD46-expressing Vero cells were necessary to shift it in the majority of the MV RNA. To verify the importance of these observations for human infections, we examined MV entry into peripheral blood mononuclear cells and observed that viruses with asparagine 481 H proteins infect these cells more efficiently.
Schneider
Urs
U
Molecular Medicine Program, Mayo Foundation, Rochester, Minnesota 55905, USA.
von Messling
Veronika
V
Devaux
Patricia
P
Cattaneo
Roberto
R
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D006023:Glycoproteins / Q000378:metabolism*; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008457:Measles / Q000821:virology; D008459:Measles virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D051916:Membrane Cofactor Protein; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface; D011991:Receptors, Virus / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014709:Vero Cells
D015703:Antigens, CD; C497857:CD46 protein, human; D006023:Glycoproteins; D006389:Hemagglutinins, Viral; D007136:Immunoglobulins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C000604059:SLAMF1 protein, human; C032397:hemagglutinin protein G, measles virus; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1