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Journal of Virology, October 2006, p. 9361-9370, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.01034-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Canine Distemper Virus Uses both the Anterograde and the Hematogenous Pathway for Neuroinvasion

INRS-Institut Armand-Frappier, University of Quebec, Laval, Quebec, Canada,¹ Virology and Gene Therapy Graduate Track, Mayo Clinic College of Medicine, Rochester, Minnesota²

Received 19 May 2006/ Accepted 11 July 2006

Canine distemper virus (CDV), a member of the Morbillivirus genus that also includes measles virus, frequently causes neurologic complications, but the routes and timing of CDV invasion of the central nervous system (CNS) are poorly understood. To characterize these events, we cloned and sequenced the genome of a neurovirulent CDV (strain A75/17) and produced an infectious cDNA that expresses the green fluorescent protein. This virus fully retained its virulence in ferrets: the course and signs of disease were equivalent to those of the parental isolate. We observed CNS invasion through two distinct pathways: anterogradely via the olfactory nerve and hematogenously through the choroid plexus and cerebral blood vessels. CNS invasion only occurred after massive infection of the lymphatic system and spread to the epithelial cells throughout the body. While at early time points, mostly immune and endothelial cells were infected, the virus later spread to glial cells and neurons. Together, the results suggest similarities in the timing, target cells, and CNS invasion routes of CDV, members of the Morbillivirus genus, and even other neurovirulent paramyxoviruses like Nipah and mumps viruses.

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