High pathogenicity of wild-type measles virus infection in CD150 (SLAM) transgenic mice.
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.
Sellin
Caroline I
CI
INSERM U404, 21 Ave. Tony Garnier, 69365 Lyon, France.
Davoust
Nathalie
N
Guillaume
Vanessa
V
Baas
Dominique
D
Belin
Marie-Françoise
MF
Buckland
Robin
R
Wild
T Fabian
TF
Horvat
Branka
B
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015703:Antigens, CD; D020805:Central Nervous System Viral Diseases / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000627:therapeutic use; D008457:Measles / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008459:Measles virus / Q000472:pathogenicity; D051379:Mice; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D000914:Antibodies, Viral; D015703:Antigens, CD; D006023:Glycoproteins; D007136:Immunoglobulins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C000604059:SLAMF1 protein, human; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1