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Journal of Virology, August 1999, p. 6916-6922, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The H Gene of Rodent Brain-Adapted Measles Virus Confers Neurovirulence to the Edmonston Vaccine Strain

W. Paul Duprex,1,* Iain Duffy,1 Stephen McQuaid,2 Louise Hamill,1 S. Louise Cosby,1,2 Martin A. Billeter,3 Jürgen Schneider-Schaulies,4 Volker ter Meulen,4 and Bert K. Rima1

School of Biology and Biochemistry, The Queen's University of Belfast, Belfast BT9 7BL,1 and Neuropathology Laboratory, Royal Group of Hospitals Trust, Belfast BT12 6B1,2 Northern Ireland, United Kingdom; Institut fur Molekularbiologie, Abteilung I, Universität Zürich, Hönggerberg, 8093 Zürich, Switzerland3; and Institute for Virology and Immunobiology, University of Würzburg, D-97078 Würzburg, Germany4

Received 11 March 1999/Accepted 3 May 1999

Molecular determinants of neuropathogenesis have been shown to be present in the hemagglutinin (H) protein of measles virus (MV). An H gene insertion vector has been generated from the Edmonston B vaccine full-length infectious clone of MV. Using this vector, it is possible to insert complete H open reading frames into the parental (Edtag) background. The H gene from a rodent brain-adapted MV strain (CAM/RB) was inserted into this vector, and a recombinant virus (EdtagCAMH) was rescued by using a modified vaccinia virus which expresses T7 RNA polymerase (MVA-T7). The recombinant virus grew at an equivalent rate and to similar titers as the CAM/RB and Edtag parental viruses. Neurovirulence was assayed in a mouse model for MV encephalitis. Viruses were injected intracerebrally into the right cortex of C57/BL/6 suckling mice. After infection mice inoculated with the CAM/RB strain developed hind limb paralysis and ataxia. Clinical symptoms were never observed with an equivalent dose of Edtag virus or in sham infections. Immunohistochemistry (IHC) was used to detect viral antigen in formalin-fixed brain sections. Measles antigen was observed in neurons and neuronal processes of the hippocampus, frontal, temporal, and olfactory cortices and neostriatum on both sides of symmetrical structures. Viral antigen was not detected in mice infected with Edtag virus. Mice infected with the recombinant virus, EdtagCAMH, became clinically ill, and virus was detected by IHC in regions of the brain similar to those in which it was detected in animals infected with CAM/RB. The EdtagCAMH infection had, however, progressed much less than the CAM/RB virus at 4 days postinfection. It therefore appears that additional determinants are encoded in other regions of the MV genome which are required for full neurovirulence equivalent to CAM/RB. Nevertheless, replacement of the H gene alone is sufficient to cause neuropathology.

* Corresponding author. Mailing address: School of Biology and Biochemistry, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Rd., Belfast BT9 7BL, Northern Ireland, United Kingdom. Phone: 1232 272060. Fax: 1232 236505. E-mail: p.duprex{at}qub.ac.uk.

Journal of Virology, August 1999, p. 6916-6922, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.