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Journal of Virology, January 2002, p. 392-396, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.392-396.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

A Single Amino Acid Change in the Nuclear Localization Sequence of the nsP2 Protein Affects the Neurovirulence of Semliki Forest Virus

John K. Fazakerley,1* Amanda Boyd,1 Marja L. Mikkola,2 and Leevi Kääriäinen2

Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh, United Kingdom,1 Institute of Biotechnology, University of Helsinki, Helsinki, Finland2

Received 11 June 2001/ Accepted 10 October 2001

The replicase protein nsP2 of Semliki Forest virus (SFV) has a 648RRR nuclear localization signal and is transported to the nucleus. SFV-RDR has a single amino acid change which disrupts this sequence and nsP2 nuclear transport. In BHK cells, SFV4 and SFV-RDR replicate to high titers, but SFV-RDR is less virulent in mice. We compared the replication of SFV4 and SFV-RDR in adult mouse brain. Both SFV4 and SFV-RDR were neuroinvasive following intraperitoneal inoculation. SFV4 spread rapidly throughout the brain, whereas SFV-RDR infection was confined to small foci of cells. Both viruses infected neurons and oligodendrocytes. Both viruses induced apoptosis in cultured BHK cells but not in the cells of the adult mouse brain. SFV-RDR infection of mice lacking alpha/beta interferon receptors resulted in widespread virus distribution in the brain. Thus, a component of the viral replicase plays an important role in the neuropathogenesis of SFV.

* Corresponding author. Mailing address: Laboratory for Clinical and Molecular Virology, Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, United Kingdom. Phone: 44 131 650 6160. Fax: 44 131 650 6511. E-mail: John.Fazakerley{at}ed.ac.uk.

Journal of Virology, January 2002, p. 392-396, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.392-396.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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