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Journal of Virology, July 2006, p. 6420-6429, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.00209-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

High Pathogenicity of Wild-Type Measles Virus Infection in CD150 (SLAM) Transgenic Mice

INSERM U404, Immunobiology of Viral Infections and Molecular Basis of Paramyxovirus Entry Teams, Lyon 69365, France,¹ Université Claude Bernard Lyon 1, IFR128 BioSciences Lyon-Gerland, Lyon, France,² INSERM U433, Neurovirology and Inflammation, Lyon 69372, France,³ Faculté de Médecine Laennec, IFR19, Lyon 69372, France,⁴ Institut de Biologie et Chimie des Protéines, IFR128 BioSciences Lyon-Gerland, Lyon 69357, France⁵

Received 29 January 2006/ Accepted 12 April 2006

Measles virus (MV) infection causes an acute childhood disease, associated in certain cases with infection of the central nervous system and development of a severe neurological disease. We have generated transgenic mice ubiquitously expressing the human protein SLAM (signaling lymphocytic activation molecule), or CD150, recently identified as an MV receptor. In contrast to all other MV receptor transgenic models described so far, in these mice infection with wild-type MV strains is highly pathogenic. Intranasal infection of SLAM transgenic suckling mice leads to MV spread to different organs and the development of an acute neurological syndrome, characterized by lethargy, seizures, ataxia, weight loss, and death within 3 weeks. In addition, in this model, vaccine and wild-type MV strains can be distinguished by virulence. Furthermore, intracranial MV infection of adult transgenic mice generates a subclinical infection associated with a high titer of MV-specific antibodies in the serum. Finally, to analyze new antimeasles therapeutic approaches, we created a recombinant soluble form of SLAM and demonstrated its important antiviral activity both in vitro and in vivo. Taken together, our results show the high susceptibility of SLAM transgenic mice to MV-induced neurological disease and open new perspectives for the analysis of the implication of SLAM in the neuropathogenicity of other morbilliviruses, which also use this molecule as a receptor. Moreover, this transgenic model, in allowing a simple readout of the efficacy of an antiviral treatment, provides unique experimental means to test novel anti-MV preventive and therapeutic strategies.

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