An antigen related to mammalian type-C RNA viral p30 proteins was shown by the use of anti-p30 sera and the indirect immunofluorescence method to be present in the kidneys and spleen in a fulminant fatal case of human systemic lupus erythematosus and to be located in the glomeruli, the site of active lupus diffuse glomerulonephritis.Systemic lupus erythematosus is widely held to be a prototype of human systemic autoimmune disease. The possibility of viral etiology is raised by the study of the autoimmune New Zealand mouse model of systemic lupus (1), since it has been shown that the development of the lupus-like immunecomplex glomerulonephritis of these mice is related to the expression of an endogenous murine type-C RNA virus (2, 3). Type-C RNA virus genes are widely distributed in the vertebrate animal kingdom, are transmitted vertically, apparently as cellular genes, and, although usually covert, are expressed by malignant cells and normal cells of several animal species (4, 5). The structural proteins of different type-C viruses are known to have several kinds of antigenic determinants, termed group-or intraspecies-specific (6, 7), interspecies-specific, and type-specific determinants. Interspecies-specific determinants (8) coexisting with intraspecies determinants (9) are present in the two major structural proteins of mammalian type-C viruses, the p27 to p30 (10) major internal protein of approximately 30,000 daltons (9, 11-13) and the gp69/71 major envelope glycopeptides (13-15), as well as the viral reverse transcriptase (16-18). The study of the interspecies determinants of purified p30 proteins shows immunological cross-reaction between all species of mammalian type-C viruses tested (11,15,19,20), including murine, feline, endogenous feline (RD-114), and woolly monkey viruses (21), and also distinguishable sets of interspecies determinants that are shared by closely related viruses, murine and feline (21-23), and baboon (endogenous primate) (23, 24), woolly monkey and gibbon ape (infectious primate) (23,25,26), and murine, feline, and infectious primate viruses (21, 23). A high degree of aminoacid sequence homology is found in the p,30 proteins of closely related mammalian type-C viruses (27). The development of assays for type-C viral nucleic acids and proteins advances the search for putative human type-C viruses; recent reports indicate that type-C virus genetic information is expressed in human tissues. Type-C virus-like particles are seen in normal human placentas by careful electron microscopic study (28) (31, 32); infectious primate virus-related reverse transcriptase (33), p30 protein antigen (34), and nucleic-acid sequences (35) are identifiable in cultured human leukemia cells; and both endogenous and infectious primate, as well as murine, virus-related p30 protein antigens are present in relatively high concentration in extracts of tissues obtained from patients with systemic lupus erythematosus (36). It has been reported also that an interspecies antigen recognized by antisera aga...
Postmortem study of proliferative glomerulonephritis associated with human systemic lupus has previously shown that an antigen related to mammalian type C RNA viral core (p30) (1, 2). We attempt to extend this finding by examining the immune deposits for the presence of a type C virus antibody. Human Igs were sequentially eluted from the lupus glomerular immune deposits and were assayed for anti-p3O antibody activity against purified viral p30 protein antigens of mammalian type C viruses. A sensitive enzymoimmunoassay was developed for detection and measurement of anti-p30 antibodies. Human Igs showing specific anti-p30 antibody activity by this assay were eluted from the glomerular immune deposits in two patients with lupus proliferative glomerulonephritis known from previous work to contain deposits of viral p30-related antigen in the same tissue lesions. This investigation adds support for the hypothesis, stemming from studies of the murine model of systemic lupus (3,4), that expression of type C viral antigen may be involved in the multifactorial pathogenesis of proliferative glomerulonephritis associated with human systemic lupus.MATERIALS AND METHODS Viruses. The following viruses purified by twice banding in sucrose gradients were provided by S. A. Mayyasi and K. A.
We find that 12 of 14 specimens of normal human term placentas analyzed by one-or two-dimensional electrophoresis and immunoblotting contain a protein or polypeptide of -30,000 daltons that is antigenically cross-reactive with p30 core protein of the simian sarcoma-associated virus/gibbon ape leukemia virus primate retrovirus group and is physicochemically similar to reference murine and primate type C retrovirus p30s. This finding may lead to an understanding of endogenous type C retrovirus gene expression in humans.Endogenous type C retroviruses are present in many mammalian species, including subhuman primates (1-4) among which the baboon (1, 5) has the closest evolutionary relation to man. These endogenous viruses exist as stable DNA proviruses that are integrated into the chromosomal DNA and are transmitted along with cellular genes in a Mendelian manner.
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