Morbillivirus Receptors and Tropism: Multiple Pathways for Infection

Sato, Hiroki; Yoneda, Misako; Honda, Tomoyuki; Kai, Chieko

Previous studies have located the MeV binding site on CD46 to the SCR1 and SCR2 domains of the receptor (Buchholz et al., 1997; Hsu et al., 1997; Casasnovas et al., 1999; Christiansen et al., 2000 ; Figure 2 ). Functional studies in vitro have suggested that signaling via CD46 is an important component of MeV pathogenesis. For example, the high degree of interaction between MeV-H and CD46 results in downregulation of CD46 from the surface of infected cells, rendering them more sensitive to C3b-mediated complement lysis (Schneider-Schaulies et al., 1995a,b; Schnorr et al., 1995) . Interestingly, CD46-mediated immunosuppression in MeV infection has been reported. One mechanism involves inhibiting activation-induced expression of interleukin (IL)-12, which is essential for the generation of successful effector T-cell responses, by cross-linking CD46 on the surface of monocytes by MeV (Karp et al., 1996; Galbraith et al., 1998; Karp, 1999; Kurita-Taniguchi et al., 2000) . Interaction of MeV-H and CD46 also induces IL-10, leading to inhibition of the contact hypersensitivity reaction (Marie et al., 2002) . In contrast, MeV binding to CD46 induces IFN production, which further triggers the early antiviral immune response Naniche et al., 2000) .