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Journal of Virology, August 2002, p. 7460-7467, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7460-7467.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Efficiency of Measles Virus Entry and Dissemination through Different Receptors

Urs Schneider,,{dagger} Veronika von Messling, Patricia Devaux, and Roberto Cattaneo*

Molecular Medicine Program, Mayo Foundation, Rochester, Minnesota 55905

Received 20 December 2001/ Accepted 29 April 2002

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.


* Corresponding author. Mailing address: Molecular Medicine Program, Mayo Foundation, 200 First St. SW, Rochester, MN 55905. Phone: (507) 284-0171. Fax: (507) 266-2122. E-mail: cattaneo.roberto{at}mayo.edu.

{dagger} Present address: Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg D-79104, Germany.


Journal of Virology, August 2002, p. 7460-7467, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7460-7467.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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