Dr. Joe McKellar et al. from IRIM (Montpellier, France) have just elucidated a modality of interferon-inducible MX1 against Influenza A with FAST of The Twinkle Factory.

Influenza A virus

Influenza A virus – by CDC Influenza Laboratory

Myxovirus resistance protein (MX1) is an enzyme of the antiviral response induced by interferons in the host infected by influenza A virus (IAV).  MX1 is well-known to inhibit influenza virus infection by impairing the early stages of viral transcription / replication.  The team have noticed that this early restriction was only partial, though a strong inhibition of overall viral production was observed.  Indeed, relatively high levels of IAV mRNAs and proteins are still observed in the presence of MX1 proteins but additional inhibition processes occurs at later stages of IAV life cycle.  In most MX1-expressing cells, significant amounts of Influenza A viral ribonucleoprotein complexes (vRNPs) are still exported from the nucleus to the cytoplasm.  However, vRNPs were found further sequestrated in large clusters in the vicinity of the microtubule organization center.  And they are no more available for downstream processing.  In conclusion, this study provides the first evidence of IAV vRNPs being re-routed and accumulated away from the plasma membrane, through the coordinated action of MX1 restriction protein, dynein and the microtubule network.

MX1 fluorescence live imaging with FAST was instrumental in their work. Small-sized, FAST tag does not impact MX1 antiviral activity contrarily to GFP. It enables multi-hour live monitoring over the course of the infection.  And it allowed highlighting the transient association of MX1 to vRNP-Rab11a trafficking complexes from ~7 h-7h30 to ~10 h-10h30 post-infection.  The very transient nature of the colocalization between HsMX1 and viral proteins during the course of IAV infection most certainly explains why this was never reported before.  Besides, this work provides the first third-party application of N871b (a red-shifted FAST fluorogenic ligand) initially disclosed by Dr M. Baranov (Moscow, Russia).

Stain different. Tag FAST!

More reading

McKellar, J., García de Gracia, F., Aubé, C., Chaves Valadão, A. L., Tauziet, M., Arnaud-Arnould, M., … & Goujon, C. (2024). Human MX1 orchestrates the cytoplasmic sequestration of neo-synthesized influenza A virus vRNPs. bioRxiv, 2024-02. (doi.org/10.1101/2024.02.22.581565)