I IFN response. DsDNA could also be sensed by DNA-dependent activator of IFN-regulatory factors (DAI); DNA:RNA hybrids could be recognized by TLR-9 The recognition of nucleic acids through PRRs provides a very efficient strategy to fight against viral infections, at the same time imposing the host to a risk due to the possibility of recognizing self-nucleic acids and promotion of autoimmunity. Not surprisingly, HERVs have been found to be associated with different autoimmune and inflammatory diseases, such as multiple sclerosis, amyotrophic lateral sclerosis (ALS), systemic lupus erythematosus (SLE), rheumathoid arthritis (RA), Sjögren syndrome (SS). On a protein level, a direct interaction between TLRs and certain HERV proteins has been shown. For example, the surface unit of HERV-W Env (also known as Multiple sclerosis-associated retroviral element (MSRV) env) was found to bind to TLR4 and CD14, stimulating the production of pro-inflammatory cytokines including IL-1β, IL-6, and TNFα. HERV-W Env can trigger a maturation process in human dendritic cells, endowing them with the capacity to support a Th1-like type of Th cell differentiation. Immunological studies have shown some evidence for T cell immune responses against HERVs in HIV-infected individuals. The hypothesis that HIV induces HERV expression in HIV-infected cells led to the proposal that a vaccine targeting HERV antigens could specifically eliminate HIV-infected cells. The potential advantage of this novel approach is that, by using HERV antigens as surrogate markers of HIV-infected cells, it could circumvent the difficulty inherent in directly targeting notoriously diverse and fast-mutating HIV antigens. Techniques for characterizing ERVs Whole genome sequencing Example: A porcine ERV (PERV) Chinese-born minipig isolate, PERV-A-BM, was sequenced completely and along with different breeds and cell lines in order to understand its genetic variation and evolution. The observed number of nucleotide substitutions and among the different genome sequences helped researchers determine an estimate age that PERV-A-BM was integrated into its host genome, which was found to be of an evolutionary age earlier than the European-born pigs isolates. Chromatin immunoprecipitation with sequencing (ChIP-seq) This technique is used to find histone marks indicative of promoters and enhancers, which are binding sites for DNA proteins, and repressed regions and trimethylation. DNA methylation has been shown to be vital to maintain silencing of ERVs in mouse somatic cells, while histone marks are vital for the same purpose in embryonic stem cells (ESCs) and early embryogenesis. Applications Constructing phylogenies Because most HERVs have no function, are selectively neutral, and