The neural cell adhesion molecule is a receptor for rabies virus

被引:258
作者
Thoulouze, MI
Lafage, M
Schachner, M
Hartmann, U
Cremer, H
Lafon, M
机构
[1] Inst Pasteur, Unite Neurovirol & Regenerat Syst Nerveux, Grp Neuroimmunol Virale, Dept Virol, F-75724 Paris 15, France
[2] Univ Mediterranee, INSERM, CNRS, LGPD,IBDM, Marseille, France
[3] Univ Hamburg, Zentrum Mol Neurobiol, Hamburg, Germany
[4] Univ Dusseldorf, Inst Genet, D-4000 Dusseldorf, Germany
关键词
D O I
10.1128/JVI.72.9.7181-7190.1998
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Previous reports strongly suggest that, in addition to the nicotinic acetylcholine receptor, rabies virus can use other, as-yet-unidentified receptors, We found that laboratory cell lines susceptible to rabies virus infection express the neural cell adhesion molecule (NCAM) (CD56) on their surface, whereas resistant cells do not, supporting the idea that NCAM could be a rabies virus receptor. We observed that (i) incubation with rabies virus decreases the surface expression of NCAM; (ii) treatment of susceptible cells with heparan sulfate, a ligand for NCAM, or with NCAM antibodies significantly reduces the rabies virus infection; and (iii) preincubation of rabies virus inoculum with soluble NCAM protein as a receptor decoy drastically neutralizes the capacity of rabies virus to infect susceptible cells. Moreover, we demonstrated that transfection of resistant L fibroblasts with the NCAM-encoding gene induces rabies virus susceptibility whereas absence of NCAM in the primary cortical cell cultures prepared from NCAM-deficient mice reduces the rabies virus infection and virus production. This provides evidence that NCAM is an in vitro receptor for the rabies virus, Moreover, the in vivo relevance for the use of NCAM as a receptor was demonstrated by the infection of NCAM-deficient mice, in which rabies mortality was delayed and brain invasion by rabies virus was drastically restricted. Our results showed that NCAM, which is expressed mainly in the adult nervous system, plays an important role in rabies infection. However, it cannot be excluded that receptors other than NCAM are utilized. Thus, the description of NCAM as a new rabies virus receptor would be another example of the use by viruses of more than one receptor to gain entry into the host.
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页码:7181 / 7190
页数:10
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