Microbial invaders often have distinct molecular patterns (referred to as pathogen associated molecular patterns, or PAMPs) that are quickly recognised by host innate immune defences. There are different types of germ-line encoded pattern recognition receptors (PRRs) such as those belonging to the Toll-like receptor (TLR) family found on the surface of cells, endosomes, and within the cytoplasm. These PRRs bind to a pathogen-associated ligand and activate a signalling cascade resulting in the expression of genes that induce inflammation as well as modulate the adaptive immune response. Innate immune recognition sensing by these receptors are not non-specific. For example, TLR-5 specifically recognises the molecular patterns of bacterial flagellin, TLR-4 responds to lipopolysaccharides found in Gram-negative bacteria, and the ligand of TLR-7 is single-stranded RNA. Double-stranded RNA that result from viral infections are specifically sensed by PRRs like TLR-3 and RIG-I with subsequent downstream effects that induce an antiviral state, such as the production of type I interferons (IFNs), followed by activation of antiviral restriction factors and natural killer cells. There is emerging research that shows how expressed ERVs may activate such immune signalling pathways, with consequences for many inflammatory diseases.

The immune system must be able to distinguish between foreign and self antigens in order to protect host tissue integrity. During development, immune cells that react too strongly to self antigens are deleted by apoptosis. Because ERVs are part of the host, ERVs are technically self antigens. However, immune cells that undergo loss of self-tolerance is characteristic of autoimmune disease, and the upregulation of ERVs in many cancers may contribute to its inflammatory pathological state.

Tara Hurst and Gkikas Magiorkinis have written a review in the Journal of General Virology discussing how ERVs activate innate immune sensing pathways and the potential implications for human disease.

Read the review paper here: Activation of the innate immune response by endogenous retroviruses

-- Audrey Lin