Spontaneous aggregation of the anti-viral MAVS protein in systemic lupus erythematosus: a possible cause of excessive type I interferon production

Excerpt

Patients with systemic lupus erythematosus (SLE) often have evidence of excessive type I interferon production, with increased interferon levels and activation of interferon-inducible genes (interferon signature). The mitochondrial adaptor protein MAVS (also known as IPS1, VISA or CARDIF) is a key intermediary in the RIG-I pathway, where viral RNA triggers a conformational change in RIG-I, leading to MAVS activation and activation of IKK and TBK1, with subsequent interferon production driven by IRF-3 and NFκB activation and translocation. A recent report using in vitro methods demonstrated that MAVS may form large prion-like aggregates which might stimulate IFN-I activation in a potent and prolonged fashion [1]. We wondered whether such aggregates might be detectable ex vivo in SLE patients, and whether they might play a role in the sustained increased production of IFN-I. The aim was to determine whether aggregated MAVS protein is present in blood cells from SLE patients. …