Endogenous retroviruses are known to represent 8% of the Human genome. HERV-W family retains elements expressing an envelope protein (Env), which activates a pro-inflammatory and autoimmune cascade through interaction with Toll-Like receptor 4 (TLR4). This Env protein was evidenced in brain lesions, sera and circulating mononuclear cells of patients with Multiple Sclerosis (MS)¹. Thus, all the background science from the past two decades that has brought independent confirmations and reproductions of an involvement of HERV-W in MS ² convinced us to further study its association with other “autoimmune diseases”. If no association was found when testing series of patients with rheumatoid arthritis³ or systemic lupus¹, about one-third of sera from patients with T1D revealed positive for the HERV-W Envelope antigen. We therefore further explored whether this immunopathogenic endogenous protein could be expressed in pancreas from T1D versus controls, which revealed positive in about 40% of first pilot series, and are now preparing to extend these analyses to larger number of serum, PBMC and pancreas samples. In parallel, we are developing an HERV-W-Env induce mouse model of diabetes for pre-clinical studies with an anti-Env neutralizing humanized antibody.

References:

1. Perron H, Germi R, Bernard C, et al. Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease. Mult Scler. 2012; 18: 1721-36.

2. Dolei A and Perron H. The multiple sclerosis-associated retrovirus and its HERV-W endogenous family: a biological interface between virology, genetics, and immunology in human physiology and disease. J Neurovirol. 2009; 15: 4-13.

3. Gaudin P, Ijaz S, Tuke PW, et al. Infrequency of detection of particle-associated MSRV/HERV-W RNA in the synovial fluid of patients with rheumatoid arthritis. Rheumatology (Oxford). 2000; 39: 950-4.