Treatment of Ebola virus infections with inhibitors of TLR4

Abstract

Ebola virus (EBOV) infection is associated with modulation of cytokine expression in infected patients. EBOV has been shown to interact directly with immune cells (at minimum with macrophages and dendritic cells) and modulation of cytokine expression has also been observed in vitro, which is similar to that in vivo. The modulation of cytokine expression observed in vitro was independent of virus infection and the glycoprotein GP1,2 was shown to be necessary and sufficient for cytokine modulation. Interestingly, similar changes in gene expression were observed in cells treated with lipopolysaccharide (LPS). As evidence suggests that GP1,2 and LPS use the same receptor, it is tempting to evaluate whether compounds that can inhibit signal transduction by LPS, e.g., TAK-242, can also reduce EBOV-induced pathogenesis.