Although the neural cell adhesion molecule (NCAM) -140 and -180 have been shown to serve as a receptor for rabies virus (RV), it was not known whether the other major isoform of NCAM, GPI-anchored NCAM-120 functions as RV receptor. In this study, we have established HEp2 cells stably expressing NCAM-120 or NCAM-140, and their susceptibilities to RV infection were compared. The results demonstrated that NCAM-120 served as virus attachment protein; however, the cells expressing NCAM-120 did not support efficient RV replication. Furthermore, the level of IFN-beta mRNA was apparently elevated in NCAM-120 expressing cells but not in NCAM-140 expressing cells, suggesting that GPIanchored NCAM-120 suppressed RV replication via induction of IFN-beta even though NCAM-120 was able to promote virus penetration into the cells. (c) 2006 Elsevier Masson SAS. All rights reserved.