MEASLES VIRUS-INDUCED DOWN-REGULATION OF CD46 IS ASSOCIATED WITH ENHANCED SENSITIVITY TO COMPLEMENT-MEDIATED LYSIS OF INFECTED-CELLS

CD46, the major component of the measles virus (MV) receptor complex a nd a member of the regulators of complement activity (RCA) gene cluste r, is down-regulated in MV-infected cells. We investigated whether the reduction of surface CD46 correlates with enhanced sensitivity of lym phoid and monocytic cells to lysis by activated complement. On human U 937 cells, acutely or persistently infected with MV-Edmonston (ED) vac cine strain, infection-dependent down-regulation of CD46 confers sensi tivity to activated complement, regardless of the pathway of activatio n and the specificity of the activating antibodies. Interestingly, dow n-regulation of CD46 alone is sufficient to confer susceptibility of c ells to complement lysis despite the continued surface expression of o ther RCA proteins such as CD35 and CD55. In primary cultures, both per ipheral blood lymphocytes and macrophages are efficiently lysed in the presence of complement activated via the alternative pathway after MV infection. In contrast to the MV-ED infection, infection of cells wit h the lymphotropic MV wild-type strain WTF does not down-regulate CD46 . Cells infected with MV-WTF do not exhibit enhanced susceptibility to complement lysis. These data suggest that MV strains similar to WTF t hat do not downregulate CD46 may have an enhanced potential for replic ation and dissemination within the human host, whereas complement-medi ated elimination of cells infected with CD46-down-regulating strains o f MV, such as ED, may limit the spread of MV infection, and could thus represent an attenuating factor for MV.