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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,
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 (377R
Q and
378M
K), Nc32 (388G
S), K71 (492E
K and 550S
P), and K29
(535E
G). 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 195G
R and 200S
N, 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.

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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