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Journal of Virology, February 2000, p. 1364-1372, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Lymphatic Dissemination and Comparative Pathology of Recombinant Measles Viruses in Genetically Modified Mice

Branka Mrkic,1 Bernhard Odermatt,2 Michael A. Klein,3 Martin A. Billeter,1 Jovan Pavlovic,4 and Roberto Cattaneo1,5,*

Molecular Biology Institute,1 Pathology Institute,2 Neuropathology Institute,3 and Medical Virology Institute,4 University of Zurich, Zurich, Switzerland, and Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota5

Received 23 July 1999/Accepted 20 October 1999

The dissemination of the Edmonston measles virus (Ed-MV) vaccine strain was studied with genetically modified mice defective for the alpha/beta interferon receptor and expressing human CD46 with human-like tissue specificity and efficiency. A few days after intranasal infection, macrophages expressing Ed-MV RNA were detected in the lungs, in draining lymph nodes, and in the thymus. In lymph nodes, large syncytia which stained positive for viral RNA and for macrophage surface marker proteins were found and apoptotic cell death was monitored. In the thymus, smaller syncytia which stained positive for macrophage and dendritic cell markers were detected. Thus, macrophages appear to be the main vectors for dissemination of MV infection in these mice; human macrophages may have a similar function in the natural host. We then compared the pathogenicities of two recombinant viruses lacking the C or V nonstructural proteins to that of the parental strain, Ed-MV. These viruses were less effective in spreading through the lymphatic system and, unlike Ed-MV, were not detected in the liver. After intracerebral inoculation the recombinant viruses caused lethal disease less often than Ed-MV and induced distinctive patterns of gliosis and inflammation. Ed-MV was reisolated from brain tissue, but its derivatives were not. C- and V-defective viruses should be considered as more-attenuated MV vaccine candidates.

* Corresponding author. Mailing address: Molecular Medicine Program, Mayo Clinic, Guggenheim 18, 200 First St. SW, Rochester, MN 55905. Phone: (507) 284-0171. Fax: (507) 266-4797. E-mail: cattaneo.roberto{at}mayo.edu.

Journal of Virology, February 2000, p. 1364-1372, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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