been reported to have superantigen activity (i.e. polyclonal T and B cell activation regardless of the specifity of their antigen receptor). It has also been shown that in vitro binding of the EBV gp350 protein caused activation of MSRVenv and syncytin-1 in B-cells, monocytes, macrophages and in astrocytes - cells that are involved in pathogenesis of multiple sclerosis. Monocytes, especially after their differentiation into macrophages, appeared to be the most responsive to EBVgp350, expressing even higher levels of HERV-Wenv than B cells.This finding is concordant with another study, which demonstrated that during infectious mononucleosis EBV promoted the strongest activation of HERV-W/MSRV expression in monocytes compared to other blood cell types. Immune response to HERVs Despite having been integrated into genomes of vertebrates for millions of years, ERVs represent an intermediate stage between exogenous viruses and the host genome; it is suggested that immunological tolerance to HERV-derived proteins and peptides is imperfect due to the epigenetic silencing of HERV in the thymus and bone marrow, which prevents deletion of all HERV-specific T and B cells. As evidence of this, immunization of non-human primates with ERV-derived antigens mounted robust polyfunctional cytotoxic T cell response as well as high antibody titers. According to phylogenetic studies, among 30 HERV families existing in the human genome, HERV-K (HML-2) elements which integrated most recently are the most intact and biologically active forms. HERV-K env and HERV-H env, considered to be a new class of tumor-associated antigens, have been found to promote strong cytotoxic T-cell responses in patients with various types of cancers. On a level of the innate immune sensing of nucleic acids, single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA) derived from endogenous retroviruses are recognized by pattern recognition receptors (PRRs). SsRNAs can be sensed by Toll-like receptors TLR-7 and TLR-8, resulting in secretion of IFN-α by stimulated dendritic cells (DCs) and macrophages, which was observed for ssRNAs derived from HIV-1. DsRNAs might be one of the most immunogenic nucleic acid pathogen-associated molecular patterns (PAMPs), since they are not found in cells in a normal state. HERV-derived dsRNA can be recognized by TLR-3, RIG-I and MDA5; RIG-I and MDA5 are known to induce a type I IFN response. When retrotranscribed into DNA, retroviruses can be sensed by cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, leading to the activation of nuclear factor-kappa B (NF-kB) and IFN regulatory factor 3 (IRF3), which in turn trigger a type