Single-cell atlas of a non-human primate reveals new pathogenic mechanisms of COVID-19
ABSTRACT
Stopping COVID-19 is a priority worldwide. Understanding which cell types are targeted by SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state influence viral entry is fundamental for accelerating therapeutic and preventative approaches. In this endeavor, we profiled the transcriptome at single-cell resolution of nine tissues from a Macaca fascicularis monkey. The distribution of SARS-CoV-2 facilitators, ACE2 and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, kidney, thyroid and liver. Co-expression analysis identified immunomodulatory proteins such as IDO2 and ANPEP as potential SARS-CoV-2 targets responsible for immune cell exhaustion. Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 expression that could promote viral entry. Our work constitutes a unique resource for understanding SARS-CoV-2 pathophysiology in two phylogenetically close species, which might guide in the development of effective treatments in humans.
Bullet points
We used a single-cell transcriptome atlas of 9 monkey tissues to study COVID-19.
ACE2+TMPRSS2+ epithelial cells of lung, kidney and liver are targets for SARS-CoV-2.
ACE2 correlation analysis shows IDO2 and ANPEP as potential therapeutic opportunities.
We unveil a link between IL6, STAT transcription factors and boosted SARS-CoV-2 entry.
Competing Interest Statement
The authors have declared no competing interest.
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