Viral induction of the human autoantigen calreticulin.
Specific but ubiquitous cytoplasmic proteins are the targets of autoantibodies such as anti-Ro/SS-A, anti-La/SS-B, and anti-calreticulin. These antibodies may be pathogenic in systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). Tissue localization of the pathogenic process could be best explained by an abnormal expression of these cytoplasmic proteins. Several factors could likely displace the host proteins 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, both in the cytoplasm and on the cell surface, was examined by a fixed cell ELISA, immunofluorescence, and immunoblotting. Infection of fibroblasts with CMV was found to increase the cell surface expression of calreticulin (p = 0.0314), but not the 60KD Ro/SS-A. Cytoplasmic expression of both the autoantigens tested increased following CMV infection. Enhanced expression of class I MHC was detected on the cell surface in 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 autoantigens. Cell surface expression of calreticulin could provide a target for circulating autoantibody and contribute to the autoimmune process.
Zhu
J
J
Department of Medicine, McGill University, Montreal General Hospital Research Institute, Quebec.
Newkirk
M M
MM
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000096:biosynthesis; D001324:Autoantigens / Q000096:biosynthesis*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D037282:Calreticulin; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000382:microbiology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D020733:RNA, Small Cytoplasmic; D011817:Rabbits; D012261:Ribonucleoproteins / Q000096:biosynthesis*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D000099207:SS-A Antigen
D000954:Antigens, Surface; D001324:Autoantigens; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D004247:DNA; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D013936:Thymidine; D014316:Tritium; D000099207:SS-A Antigen; C116006:RO60 protein, human