Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus

The 2014–2015 Ebola virus outbreak in West Africa is the largest filovirus outbreak to date.Filovirus infections in humans are acquired by direct contact with infected bodily fluid through breaks in the skin or mucosal membranes, and the virus typically targets macrophages, monocytes and dendritic cells, among other cell types.Severe infection with filoviruses can lead to viral haemorrhagic fever and other coagulation abnormalities.Filoviruses evade and alter the innate immune response through various mechanisms.Viral protein 35 (VP35) antagonizes the innate immune system by blocking signalling through RIG-I-like receptors (RLRs) and further impairing the interferon (IFN) response.VP35 can bind to double-stranded RNA (dsRNA), further suppressing the RLR-mediated IFN response, and can interact with PACT, an activator of the IFN-induced antiviral kinase protein kinase (PKR).Ebola virus VP24 can bind to karyopherin-α (KPNA) proteins, preventing their interaction with tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1), which then prevents the activation of IFN-stimulated response elements.Marburg virus VP40 blocks the activation and function of Janus kinase 1 (JAK1), inhibiting the type I IFN-induced phosphorylation of STAT1 and STAT2.Filoviruses adapt to their host in order to sustain viral replication and to subvert translational regulation mechanisms.Marburg virus VP24 can modulate the function of kelch-like ECH-associated protein 1 (KEAP1), enabling activation of antioxidant response elements (AREs) and promoting survival of virus-infected host cells.Further understanding of filoviruses is necessary to develop better therapeutics and more efficiently combat infection.