LabzInnate Lab

There is a Postdoc job available in my lab to study fundamental mechanisms of antiviral immunity, specifically in the context of viral nucleic acid sensing. Please take a look here and contact me if interested:
#immunosky #virology 🧪
www.jobs.cam.ac.uk/job/50254/

Thanks! We think the TBK1 (likely IFN-dependent) restriction therefore happens at assembly (post RNA replication anyway) but we never followed that up…it’d be cool to define that though and find out what happens to all that viral RNA 😀

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

mr bean is wearing a suit and tie and smiling while standing in front of a camera . ALT: mr bean is wearing a suit and tie and smiling while standing in front of a camera .

Excited to be heading to the @ausvirologysoc.bsky.social conference today and catching up with my fave virologists down under. I’m of course most excited about the innate immunity sessions 😉

Thanks Natalia! The most important starter pack of all 😉

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Thanks Jesse! Please add me :)

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.

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Our study sheds light on how our favourite innate immune sentinel cells trigger inflammation and control virus infections.

Stoking inflammasome fires in the COVID-19 neighborhood The cellular and molecular sources of elevated IL-1β and IL-6 in COVID-19 remain unclear. In this issue of Cell Host and Microbe, Barnett et al. determine how immune cells sense SARS-CoV-2 infection i...

We think all of those ACE2-neg macrophages will instead respond to neighbouring infected cells cell.com/cell-host-mi...,

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).

Macrophages are key players in COVID-19, so we asked the crucial questions 1) does SARS-CoV-2 need ACE2 to replicate in macrophages 2) does ACE2 enable macrophage cytokine responses?

Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release ACE2 in macrophages promotes infection that enables an intrinsic antiviral response to SARS-CoV-2.

How do macrophages sense SARS-CoV-2 infection to drive inflammation (protective or disease causing) in COVID-19? Our 2023 paper in Science Signalling helps explain 🧵
www.science.org/doi/10.1126/...

Mechanisms of antibody-dependent enhancement of infectious disease - Nature Reviews Immunology This Review discusses the different mechanisms of antibody-dependent enhancement (ADE) of infectious disease, including how antibodies can increase the pathogen load, protect bacteria from the immune ...

If you've wondered how antibodies can work against us during infectious disease, please check out our recent review in Nature Reviews Immunology:
Mechanisms of antibody-dependent enhancement of infectious disease | Nature Reviews Immunology
www.nature.com/articles/s41...