VIRAL INDUCTION OF THE HUMAN AUTOANTIGEN CALRETICULIN

Specific but ubiquitous cytoplasmic proteins are the targets of autoan tibodies such as anti-Ro/SS-A, anti-La/SS-B, and anti-calreticulin. Th ese antibodies may be pathogenic in systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). Tissue localization of the pathogenic pr ocess could be best explained by an abnormal expression of these cytop lasmic proteins. Several factors could likely displace the host protei ns to the cell surface. This study was designed to use cytomegalovirus (CMV) infected human fibroblasts (MRC-5) as a model, to test whether a viral infection would induce the expression of the human autoantigen (s). Expression of Ro/SS-A, calreticulin, and MHC class I antigens, bo th in the cytoplasm and on the cell surface, was examined by a fixed c ell ELISA, immunofluorescence, and immunoblotting. Infection of fibrob lasts with CMV was found to increase the cell surface expression of ca lreticulin (p = 0.0314), but not the 60KD Ro/SS-A. Cytoplasmic express ion of both the autoantigens tested increased following CMV infection. Enhanced expression of class I MHC was detected on the cell surface i n response to the virus infection. The expression of the autoantigens and MHC class I polypeptides, as well as the virally induced elevated mitotic rate, diminished after 24 h of infection. Viral infection was found to alter the distribution of host cell proteins, including autoa ntigens. Cell surface expression of calreticulin could provide a targe t for circulating autoantibody and contribute to the autoimmune proces s.