In addition, in vitro studies have established that MSRV/HERV-W Env and the MSRV virion can activate TLR4 on antigen presentation cells (APCs) including macrophages, dendritic cells and microglia leading to the production of a range of PICs such as IL-1β, TNFα and IL-6, which are known to play a causative role in the pathogenesis and pathophysiology of MS both in terms of microglial activation and actively provoking demyelination [166–169]. This evidence concerns the gene TNF and myeloid sarcoma.