Human Endogenous Retrovirus-R Env Glycoprotein as Possible Autoantigen in Autoimmune Disease

Abstract

It has long been discussed whether endogenous retroviruses (ERVs) are involved in the pathogenesis of autoimmune diseases. Among various human endogenous retroviruses (HERVs), we have focused on HERV-R. To investigate the biological roles of HERV-R, we earlier established transgenic rats carrying the full sequence of the viral genome. In these HERV-R rats, however, no disease occurred. Another trigger that induces autoimmunity may be essential for the recognition of HERV-R products by the immune system. Thus, in this study, we mated HERV-R rats with env-pX rats (transgenic rats carrying the env-pX gene of human T cell leukemia virus type I) that develop autoimmune diseases, and generated double transgenic (DTG) rats. In DTG rats, autoimmune diseases occurred similarly in env-pX rats. Interestingly, deposition of rat IgM but not IgG was observed on the glomerular endothelial cells. Such IgM deposition was never seen in the parental HERV-R or env-pX rats. We considered that in situ formation of immune complexes consisted of the HERV-R env glycoprotein and anti-HERV-R env IgM antibodies (Abs) in DTG rats, according to the following evidence: (1) No dense deposit, representing deposition of circulating immune complexes, was seen on glomerular endothelial cells. (2) IgM Abs reactive with HERV-R env glycoprotein were generated in the serum. (3) HERV-R env glycoprotein was expressed in the kidney, specifically on glomerular endothelial cells. (4) IgM deposition was partly colocalized with the HERV-R env glycoprotein on the glomeruli. These findings strongly suggest that the HERV-R env glycoprotein is recognized as an autoantigen in the host with autoimmune diseases.

Abnormal conformation and impaired degradation of propylthiouracil‐induced neutrophil extracellular traps: Implications of disordered neutrophil extracellular traps in a rat model of myeloperoxidase antineutrophil cytoplasmic antibody–associated vasculitis

“…Histologic scoring was carried out as previously described (14). To detect deposition of fibrinogen and immunoglobulin in glomeruli, snap‐frozen sections of the rat kidneys were processed for direct immunofluorescence staining using fluorescein isothiocyanate–labeled antibodies specific for fibrinogen (Dako), IgG (Jackson ImmunoResearch), and IgM (Jackson ImmunoResearch) as previously described (15).…”

Endogenous Retrovirus 3 – History, Physiology, and Pathology

“…ERV encoded antigens can be recognized by cytotoxic T cells ( Haist et al, 1992 ). Antibody cross-reactivity between exogenous retroviruses and ERV3 peptides have been described ( Katsumata et al, 1999 ) and ERV3 is up-regulated by cytokines in endothelial cells ( Sasaki et al, 2009 ). Indeed, ERV3 has been suggested as an auto-antigen involved in different immune-pathologies ( Takeuchi et al, 1995 ; Li et al, 1996 ; de Parseval et al, 1999 ; Blank et al, 2009 ; Nelson et al, 2010 , 2014 ; Kowalczyk et al, 2012 ).…”

Is HERV-K and HERV-W Expression Regulated by miR-155 in Kidney Transplant Patients with Human Cytomegalovirus Infection?

“…Given that miR-155-5p plays important roles in many biological pathways, more investigation is needed to further define the in vivo mRNA targets of this miRNA. Notably, increased levels of ERV transcripts have been observed in individuals with virus infections [17] and those with autoimmune diseases [26], and miR-155 is involved in these pathological processes [27]. The significance of these findings is that miR-155 exerts its regulation by limiting overproduction of HERV during viral infection and by helping to stimulate innate immunity.…”