ALTERED EXPRESSION OF HOST-ENCODED COMPLEMENT REGULATORS ON HUMAN CYTOMEGALOVIRUS-INFECTED CELLS

Human cytomegalovirus (HCMV)-infected cells persist in the presence of anti-HCMV antibody, suggesting that HCMV has evolved mechanisms to ev ade host immune defenses. Insofar as no virus-encoded complement inhib itors have been identified for HCMV, we hypothesized that HCMV infecti on may alter the expression of host-encoded cell surface complement in hibitors. Herein, we report that cell surface expression of two comple ment regulator proteins, CD55 and CD46, which are members of the regul ators of complement activation (RCA) gene cluster, increased up to eig htfold following infection of fibroblasts or glioblastoma cells with H CMV, but not after infection with HSV-1 or adenovirus. However, the ce ll surface expression of a third complement regulator, CD59, which is not a member of the RCA gene cluster, was not altered during HCMV infe ction. Functional studies using purified complement components demonst rated that up-regulation of CD55 suppressed the activity of cell-assoc iated C3 convertases on HCMV-infected cells. Furthermore, increased CD 55 expression protected infected cells from complement-mediated lysis, an effect which directly correlated with the length of HCMV infection . Increased expression of host-encoded complement regulator proteins m ay provide protection of HCMV-infected cells from the host immune resp onse in vivo, through increasing the resistance of infected cells to c omplement-mediated lysis and decreasing the deposition of C3-derived p roducts on the cell surface.