Genetic changes that affect the virulence of measles virus in a rhesus macaque model

Virology. 2008 Mar 30;373(1):39-50. doi: 10.1016/j.virol.2007.11.025. Epub 2007 Dec 21.


To identify genetic changes that lead to the attenuation of measles virus (MV), a strain of MV that is pathogenic in rhesus macaques was adapted to grow in Vero cells, Vero/hSLAM cells and, to simulate the process used to derive live attenuated vaccines, in primary chicken embryo fibroblasts (CEF). Comparison of the complete genomic sequences of the pathogenic wild-type (Davis87-wt) and four cell culture-adapted strains derived from it showed complete conservation of sequence in the Vero/hSLAM-passaged virus. Viruses adapted to Vero cells and CEF had predicted amino acid changes in the nucleocapsid protein, phosphoprotein, V protein, C protein, matrix protein, and the cytoplasmic tail of the hemagglutinin protein. All four cell culture-adapted strains, including the Vero/hSLAM cell-passaged virus, were able to productively infect Vero cells, but the peak viral titers differed. The Vero cell-adapted strains were unable to replicate in Chinese Hamster Ovary cells expressing CD46, indicating that they had not adapted to use the CD46 receptor. The Vero/hSLAM cell-passaged virus retained pathogenicity in rhesus macaques as measured by the appearance of a skin rash while the Vero cell-adapted and CEF-adapted strains had lost the ability to cause a rash. There were no significant differences in viral titers in peripheral blood mononuclear cells among monkeys infected with any of the viral stocks tested. These results identify a limited number of genetic changes in the genome of MV that lead to attenuation in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Amino Acid Substitution*
  • Animals
  • Antigens, CD / metabolism
  • CHO Cells / virology
  • Chick Embryo
  • Chlorocebus aethiops
  • Cricetinae
  • Cricetulus
  • Disease Models, Animal*
  • Female
  • Humans
  • Macaca mulatta
  • Male
  • Measles / physiopathology*
  • Measles / virology
  • Measles virus / genetics*
  • Measles virus / pathogenicity*
  • Measles virus / physiology
  • Receptors, Cell Surface / metabolism
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Vero Cells / virology
  • Virulence
  • Virus Replication


  • Antigens, CD
  • Receptors, Cell Surface
  • Signaling Lymphocytic Activation Molecule Family Member 1