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

• DOI: 10.1128/jvi.75.16.7612-7620.2001
• Publication Date: 2002-07-27T09:58:35Z
• Authors: Kerstin Moeller; Iain Duffy; Paul Duprex; Bert Rima; Rudi Beschorner; Susanne Fauser; Richard Meyermann; Stefan Niewiesk; Volker ter Meulen; Jürgen Schneider...
• Keywords: Morbillivirus

ABSTRACT 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 variants escaping from monoclonal antibodies (MAbs) Nc32 and L77 hemagglutinin (H) preserved their neurovirulence, whereas mutants MAbs K71 K29 were found be strongly attenuated (U. G. Liebert et al., J. Virol. 68:1486–1493, 1994). To investigate molecular basis these findings, we have generated a panel recombinant MVs expressing H protein CAM/RB introduced amino acid substitutions thought responsible for antibody escape and/or neurovirulence. Using viruses, identified changes conferring (377R→Q 378M→K), (388G→S), (492E→K 550S→P), (535E→G). When corresponding viruses tested brains mutations mediating did not confer differential In contrast, however, replacement two different acids, at positions 195G→R 200S→N, had described mutant set, caused change Thus, neurovirulence appear associated with same structural alterations MV protein.