Single-cell transcriptional atlas of the Chinese horseshoe bat (Rhinolophus sinicus) provides insight into the cellular mechanisms which enable bats to be viral reservoirs
bioinformatics immunology/immunity inflammation
Authors:Lili Ren et al.
Link to paper: https://www.biorxiv.org/content/10.1101/2020.06.30.175778v1
Tags: Bioinformatics, Immunology/Immunity, Inflammation
An atlas of single-cell transcriptomes across 19 organs of the Chinese horseshoe bat, a natural coronavirus reservoir, was created and made available (http://bat.big.ac.cn/)
The expression of entry receptors (including ACE2) for various zoonotic viruses was high in bat enterocytes, and was overall similar to both mouse and human
Bat primary lung fibroblasts challenged with poly I:C and Vesicular stomatitis virus express much lower PAMPs, IFNb, TNFa and IL-6 levels compared to human primary lung fibroblasts
The first bat cell atlas was created by scRNA-seq of 19 different tissues from a Chinese horseshoe bat, a natural reservoir for SARS-like coronaviruses. 182 clusters were defined comprising immune and parenchymal fractions, whose gene expression can be explored at: http://bat.big.ac.cn/. Furthermore, the expression patterns of entry receptors for various zoonotic viruses were compared in bat, human and mouse and found highly similar. Intestinal epithelium expresses high levels of various viral receptors, including ACE2. Additional comparisons of bat, mouse and human lung transcriptional profiles revealed differential expression of various genes implicated in anti-viral and anti-inflammatory response, e.g HMOX-1. Finally, VSV and poly I:C challenged bat lung fibroblasts produced lower PAMPs, IFNb, TNFa and IL-6 levels compared to their human counterparts, suggesting that a weaker response may contribute to the capacity of bats to asymptomatically carry certain viruses.
Impact for SARS-CoV2/COVID19 research efforts
- Understanding what allows bats to serve as viral reservoirs without any pathology and disease in these animals
Understanding potential transmission routes- intestine/faeces seems to be a major route for cross species transmission
In silico study / bioinformatics study
In vitro study (human and bat primary fibroblasts)
In vivo study (two male Chinese horseshoe bats)
Strengths and limitations of the paper
Novelty: First single cell bat atlas created, dataset compared against mouse and human reveals some interesting differentially regulated molecules, e.g. IRF9, HMOX-1, etc., whereas viral entry receptor expression level and tropism very similar.
Standing in the field: Confirms that CoVs are mostly detected in bat intestine (high expression of various entry receptors) indicating faeces as major dispersal route
Viral model used:Vesicular stomatitis virus for in vitro assay
Translatability:Some differentially regulated genes between bat and human implicated in anti-viral and anti-inflammatory response should be further explored
It would be great if researchers examined and compared the response of bat and human primary fibroblasts to SARS-CoV2. Additionally, exploration of anti-viral response in isolated macrophages and/or other immune cells from the bat (especially lung and gut) versus human cells would be valuable to further inspect the differences observed when comparing lung datasets
It would be relevant to know if the 2 captured bats harboured any zoonotic viruses (especially as the majority of T cells identified by scRNAseq had an activated phenotype)