Thanks @ausvirologysoc.bsky.social for a great meeting. Where else can you turn the evolution of flu A vs flu B strains as described by @marioskoutsakos.bsky.social into a dance move. Having Jenna Guthmiller here from the US was a highlight for me! See you all in Adelaide in 2026

Huge thanks to all of the people who contributed to this project including my fantastic lab, brilliant collaborators and the imaging and microscopy experts at IMB, UQ because seeing is believing.

These ACE2-pos macs CAN make new infectious virions, BUT, all those anti-viral cytokines the macs make stop new virion release. If we block cytokine induction with a TBK1 inhibitor (BX795) then we rescue ACE2-pos mac virus production.

But SARS-CoV-2 can enter ACE2-pos macs (maybe even fuse at the plasma membrane) AND trigger macrophage cytokine release.

Macrophages are of course big eaters, and we saw some virus in ACE2-neg HMDM, but we speculate it doesn’t make it into the cytosol to trigger macrophage sensors. Accordingly, ACE2-neg macs don’t make any cytokines.

Huge scRNA seq efforts from many groups found macrophages with lots of viral RNA in COVID-19 patients, but not many macrophages expressing ACE2.
So, we modelled some ACE2-neg (incl. HMDM) and ACE2-pos macs and saw that SARS-COV-2 only replicates in ACE2-pos Macs (THP-1 ACE2).