Amino acid substitutions at positions 242, 255 and 268 in rabies virus glycoprotein affect spread of viral infection
Article first published online: 20 NOV 2009
© 2009 The Societies and Blackwell Publishing Asia Pty Ltd
Microbiology and Immunology
Volume 54, Issue 2, pages 89–97, February 2010
How to Cite
Ito, Y., Ito, N., Saito, S., Masatani, T., Nakagawa, K., Atoji, Y. and Sugiyama, M. (2010), Amino acid substitutions at positions 242, 255 and 268 in rabies virus glycoprotein affect spread of viral infection. Microbiology and Immunology, 54: 89–97. doi: 10.1111/j.1348-0421.2009.00192.x
- Issue published online: 25 JAN 2010
- Article first published online: 20 NOV 2009
- Received 2 September 2009; revised 6 October 2009; accepted 28 October 2009.
- cell-to-cell spread;
- rabies virus
Rabies virus Nishigahara strain kills adult mice after intracerebral inoculation, whereas the derivative RC-HL strain does not. It has previously been reported by us that the R(G 242/255/268) strain, in which amino acids at positions 242, 255 and 268 on the G protein have been replaced by those from the Nishigahara strain in the genetic background of the RC-HL strain, kills adult mice. This indicates that these three amino acids of G protein are important for pathogenicity of the Nishigahara strain. In order to obtain insights into the mechanism by which these amino acids affect pathogenicity, in this study spread of viral infection and apoptosis-inducing ability of the attenuated RC-HL strain and the virulent R(G 242/255/268) strain were compared. RC-HL infection spread less efficiently in the mouse brain than did R(G 242/255/268) infection. However, the apoptosis-inducing abilities of both viruses were almost identical, as shown by both in vitro and in vivo experiments. It was demonstrated that cell-to-cell spread of RC-HL strain was less efficient than that of R(G 242/255/268) strain in mouse neuroblastoma cells. These results indicate that the three amino acid substitutions affect efficiency of cell-to-cell spread but not apoptosis-inducing ability, probably resulting in the distinct distributions of RC-HL and R(G 242/255/268) strain-infected cells in the mouse brain and, consequently, the different pathogenicities of these strains.