Immune system evasion

Filoviral infection also interferes with proper functioning of the innate immune system. EBOV proteins blunt the human immune system's response to viral infections by interfering with the cells' ability to produce and respond to interferon proteins such as interferon-alpha, interferon-beta, and interferon gamma.

The VP24 and VP35 structural proteins of EBOV play a key role in this interference. When a cell is infected with EBOV, receptors located in the cell's cytosol (such as RIG-I andMDA5Toll-like receptor 3 (TLR3), TLR7, TLR8 and TLR9), recognize infectious molecules associated with the virus. On TLR activation, proteins including interferon regulatory factor 3 and interferon regulatory factor 7 trigger a signaling cascade that leads to the expression of type 1 interferons. The type 1 interferons are then released and bind to the IFNAR1 and IFNAR2 receptors expressed on the surface of a neighboring cell. Once interferon has bound to its receptors on the neighboring cell, the signaling proteins STAT1 and STAT2 are activated and move to the cell's nucleusThis triggers the expression of interferon-stimulated genes, which code for proteins with antiviral properties. EBOV's V24 protein blocks the production of these antiviral proteins by preventing the STAT1 signaling protein in the neighboring cell from entering the nucleus. The VP35 protein directly inhibits the production of interferon-beta. By inhibiting these immune responses, EBOV may quickly spread throughout the body