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Journal of Virology, August 2001, p. 7612-7620, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7612-7620.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Recombinant Measles Viruses Expressing Altered Hemagglutinin (H) Genes: Functional Separation of Mutations Determining H Antibody Escape from Neurovirulence

Kerstin Moeller,1 Iain Duffy,2,dagger Paul Duprex,2 Bert Rima,2 Rudi Beschorner,3 Susanne Fauser,3 Richard Meyermann,3 Stefan Niewiesk,1 Volker ter Meulen,1,* and Jürgen Schneider-Schaulies1

Institut für Virologie und Immunbiologie, University of Würzburg, D-97078 Würzburg,1 and Institut für Hirnforschung, Universitätsklinikum Tübingen, D-72076 Tübingen,3 Germany, and School of Biology and Biochemistry, The Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland2

Received 7 March 2001/Accepted 16 May 2001

Measles virus (MV) strain CAM/RB, which was adapted to growth in the brain of newborn rodents, is highly neurovirulent. It has been reported earlier that experimentally selected virus variants escaping from the monoclonal antibodies (MAbs) Nc32 and L77 to hemagglutinin (H) preserved their neurovirulence, whereas mutants escaping MAbs K71 and K29 were found to be strongly attenuated (U. G. Liebert et al., J. Virol. 68:1486-1493, 1994). To investigate the molecular basis of these findings, we have generated a panel of recombinant MVs expressing the H protein from CAM/RB and introduced the amino acid substitutions thought to be responsible for antibody escape and/or neurovirulence. Using these recombinant viruses, we identified the amino acid changes conferring escape from the MAbs L77 (377Rright-arrowQ and 378Mright-arrowK), Nc32 (388Gright-arrowS), K71 (492Eright-arrowK and 550Sright-arrowP), and K29 (535Eright-arrowG). When the corresponding recombinant viruses were tested in brains of newborn rodents, we found that the mutations mediating antibody escape did not confer differential neurovirulence. In contrast, however, replacement of two different amino acids, at positions 195Gright-arrowR and 200Sright-arrowN, which had been described for the escape mutant set, caused the change in neurovirulence. Thus, antibody escape and neurovirulence appear not to be associated with the same structural alterations of the MV H protein.


* Corresponding author. Mailing address: Institut für Virologie und Immunbiologie, Versbacher Str. 7, D-97078 Würzburg, Germany. Phone: 49-931-2015954. Fax: 49-931-2013934. E-mail: termeulen{at}vim.uni-wuerzburg.de.

dagger Present address: H. Lee Moffitt Cancer Research Center, Tampa, Fla.


Journal of Virology, August 2001, p. 7612-7620, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7612-7620.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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