To all the coauthors, Cal Bentley-Abbot, Jack McCowan, Colin Loney, Ed Roberts and @socialinfluenza.bsky.social , thanks for all your hard work and guidance! We are grateful for the funders, reviewers, @plos.org and our many fantastic colleagues @cvrinfo.bsky.social

This work uncovers a novel way in which IAVs can exploit cell death to propagate infection. This time it does so by ensuring its continued spread after it has exhausted the life of its host cell, and the often hostile environment of the lung awaits. N/11

Is apoptosis then required for IAV direct cell to cell spread? Well, not only do IAVs frequently undergo direct cell to cell spread, but this can almost be completely prevented with the inhibition of apoptosis! N/10

💡we found that whilst apoptosis alone had no effect, TLS induction by IAVs required both virus replication and the onset of apoptosis. Overall, our data reveals that apoptosis induced through IAV replication is responsible for the triggering of TLSs. N/9

🔍Clue 3: the induction of TLSs correlated with the onset of apoptosis. Furthermore, inhibition of apoptosis prevented the ability of IAVs to induce TLSs. However, induction of apoptosis with drugs, independent of infection, did not induce TLS formation. N/9

🔎Clue 2: induction of TLSs was consistent between IAV strains having either filamentous or spherical virion morphologies. This was in despite of several curious similarities between TLSs and budding IAV filaments. N/8

🔎Clue 1: the induction of TLSs did not occur through the release of paracrine innate immune signals, but did require intracellualr IAV replication. N/7

Satisfied that TLSs could be relevant to within host IAV spread, we set out to find how IAVs were triggering their formation. For this investigation we embarked on a systematic hunt for clues, using in vitro cell culture systems. N/6

Firstly, we wanted to see if these structures formed at the natural site of IAV infection. We collaborated with the wonderful Ed Roberts lab and we could see, for the first time, evidence of TNT-like structures (TLSs) forming from infected cells within the lungs of mice. N/5

One mechanism of IAV direct cell to cell spread in vitro is through the formation of long, thin and fragile membrane connections known as Tunnelling Nanotubes (TNTs). Impressively, IAVs trigger the formation of TNTs but it was unknown how they were doing this. N/4

Direct cell to cell spread of IAVs describes the mechanisms that deliver viral genomes to new cells, independent of a cell free virus particle. This can allow infection spread even in the presence of antiviral drugs and neutralising anitbodies. N/3

@socialinfluenza.bsky.social we are fascinated about what makes IAVs infectious and what shapes it's within host spread. The complexity of this fundamental biology is underappreciated and many questions remain. A perfect example of this is the direct cell to cell spread of these viruses. N/2

For those who sadly couldn't be there, you were missed. However, fear not, for we have a pre-print available! With hopefully more updates to share soon! t.co/GyBP66ggjE

Shameless plugs: if you're at the meeting please say hello to members of our group, they are all fab:
(1) @danielweiriav.bsky.social talks about TNTs and flu in the Virus:Host Interactions Forum (Weds 2nd 14:45)
(2) Junsen Zhang has a poster in block A on pasteurising flu in milk (A036)
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