Enrichment of SARS-CoV-2 Entry Factors and Interacting Intracellular Genes in Tissue and Circulating Immune Cells.

Abhinandan Devaprasad,Aridaman Pandit

doi:10.3390/v13091757

Abstract

SARS-CoV-2 uses ACE2 and TMPRSS2 to gain entry into the cell. However, recent studies have shown that SARS-CoV-2 may use additional host factors that are required for the viral lifecycle. Here we used publicly available datasets, CoV-associated genes, and machine learning algorithms to explore the SARS-CoV-2 interaction landscape in different tissues. We found that in general a small fraction of cells express ACE2 in the different tissues, including nasal, bronchi, and lungs. We show that a small fraction of immune cells (including T cells, macrophages, dendritic cells) found in tissues also express ACE2. We show that healthy circulating immune cells do not express ACE2 and TMPRSS2. However, a small fraction of circulating immune cells (including dendritic cells, monocytes, T cells) in the PBMC of COVID-19 patients express ACE2 and TMPRSS2. Additionally, we found that a large spectrum of cells (in tissues and circulation) in both healthy and COVID-19-positive patients were significantly enriched for SARS-CoV-2 factors, such as those associated with RHOA and RAB GTPases, mRNA translation proteins, COPI- and COPII-mediated transport, and integrins. Thus, we propose that further research is needed to explore if SARS-CoV-2 can directly infect tissue and circulating immune cells to better understand the virus’ mechanism of action.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus from the Coronaviridae family that has infected more than 100 million individuals and has caused a rapidly unfolding global pandemic
We further studied the expression of angiotensinconverting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in different cell types in each of the tissues (Figures 1b–g and S1)
We first assessed the expression of ACE2 and TMPRSS2 in different tissues and cell types using 16 single-cell RNA-Seq datasets

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus from the Coronaviridae family that has infected more than 100 million individuals and has caused a rapidly unfolding global pandemic. A large number of infected individuals present no or mild symptoms and yet can spread the virus to others. Some infected individuals develop severe acute respiratory distress syndrome resulting in coronavirus disease (COVID-19). This leads to a unique dysregulation of the immune system that is accompanied by a strong inflammatory response, cytokine storm, and respiratory distress and viral sepsis [1]. There is an urgent need to understand the mechanisms of infection and pathophysiology of SARS-CoV-2

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Results

Conclusion