Thread by @VirusesImmunity

Short🧵 on study by @BenIsraelow, @ericsongg et al on “Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling”.

Take home points
1) This is a quick and versatile model of #COVID19 that can be used on any genetic bgd 🐁

rupress.org/jem/article/21…

Mice are first transduced with AAV encoding human ACE2 to allow expression of viral receptor. This makes them susceptible to infection by #SARSCoV2. (red=virus; green=epithelia; blue=nuclei)

2) In this model, type I IFN signaling does not appear to contribute to viral control. In other words, #SARSCoV2 effectively evades innate immune control by endogenous IFN signaling.

3) Instead, type I IFN signaling contributes to inflammatory leukocyte recruitment to the lung (inflammatory monocytes, T cells, NK), likely because it induces chemokines that attract these immune cells. (Note neutrophil recruitment doesn't require IFN signal)

As always, this was a great teamwork! With @tianyangmao @peowenlu @AmitMeir_hbh @FeimeiL @MiaAlfajaro Jin Wei Huiping Dong @rjhomer57 @aaronmring @WilenLab 🙏🏼

4) We also see pathogenic role of IFNs in our study on the human immune response in #COVID19. Sustained IFN responses were observed in severe patients, and elevated IFN-a correlated with viral load and mortality. @carolilucas @sneakyvirus1 @tiago21bio

nature.com/articles/s4158…

5) However, these results do not mean that early or prophylactic treatment with recombinant IFN will not work. The key is to shut down virus replication by exogenous IFN early or before viral exposure (more discussions in this paper 👇🏽). (end)

ncbi.nlm.nih.gov/pmc/articles/P…