Prion-like MAVS fibrils stitch mitochondria to promote a rapid antiviral response.

Innate immunity in host cells must be rapidly activated to combat invading microbes. Upon RIG-I activation, the transcription of type I interferons is induced within one hour in virus-infected cells. Previous studies have shown that endogenous MAVS spreads signals via aggregation on the mitochondrial membrane, whereas truncated recombinant MAVS forms prion-like filaments in vitro. How MAVS transmits signals so quickly, and the molecular architecture of its membrane aggregates, remains elusive. Here, we report that activated MAVS forms fibrils encircling its resident mitochondrion or connecting neighboring mitochondria with a "ladder-like" structure, allowing the activation of dormant MAVS on encountered mitochondria. This "intermitochondrial activation" process promotes a rapid antiviral response in cells to overcome the immediate danger caused by viruses. Moreover, stuck MAVS fibrils between mitochondria have limited cytosolic protein access and thus relay signals poorly. This study demonstrated that prion-like MAVS fibrils cluster in mitochondria to ensure a rapid antiviral response.