Speaker
Description
Recently, research efforts focus on the role of viral RNA species in the context of host antiviral signalling inhibition. Imaging studies give invaluable insights into complex RNA-protein and protein-protein interactions visualized directly at their side of action.
Among the IAV proteins the non-structural protein 1 (NS1) of influenza A virus (IAV) is described to be involved in manifold processes aiming the blockage of host defence. The interaction with double-stranded RNA and /or RNA helicase, retinoic acid inducible gene I (RIG-I), impedes the activation of transcription factors initializing antiviral signalling cascades. This block is enhanced by interacting with tripartite motif containing protein 25 (TRIM25), an ubiquitin ligase which is a mediator of innate virus recognition through the interferon regulatory factor 3 (IRF3) pathway. We found TRIM25 accumulation on NS1 cytosolic aggregates which results in diminished levels of nuclear TRIM25, which is required for the block of viral RNA elongation.
Applying confocal and super-resolution fluorescence microscopy and immunoprecipitation our findings revealed strain specific characteristics of NS1 cytosolic aggregation and confirmed localisation of TRIM25 to these structures at late stages of viral replication when comparing WT IAV and recombinant IAV lacking NS1 expression.
With the help of a sophisticated imaging approach we were able to detect IAV vRNA and TRIM25 at nanoscopic resolution combined with the diffraction limited detection of NS1 for the first time. Contrary to the postulated interaction between TRIM25 and IAV vRNA, our results evince IAV vRNA not being involved into the TRIM25-NS1 cytosolic complex in Panama/2007/1999 infected A549 cells at 16 hours post infection.
| Choose primary session | Virus host cell interaction |
|---|---|
| Choose secondary Session | Visualising Flu |
