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Journal of Virology, August 1999, p. 6916-6922, Vol. 73, No. 8
School of Biology and Biochemistry,
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.
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
*
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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