Gene Expression Profiling Reveals the Shared and Distinct Transcriptional Signatures in Human Lung Epithelial Cells Infected With SARS-CoV-2, MERS-CoV, or SARS-CoV: Potential Implications in Cardiovascular Complications of COVID-19

Frontiers in Cardiovascular Medicine

Prabhash Kumar Jha¹  Masanori Aikawa²  Arda Halu³  Aatira Vijay⁴  Shizuka Uchida⁵ 

[1] Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States;Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States;Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States;Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States;Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States;Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States;Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States;Department of Clinical Medicine, Center for RNA Medicine, Aalborg University, Copenhagen, Denmark;

关键词: SARS-CoV-2;    SARS-CoV;    MERS-CoV;    COVID-19 and transcriptome analysis;    cardiovasclar disease;   

DOI  :  10.3389/fcvm.2020.623012

来源: Frontiers

【 摘 要 】

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative virus for the current global pandemic known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 belongs to the family of single-stranded RNA viruses known as coronaviruses, including the MERS-CoV and SARS-CoV that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), respectively. These coronaviruses are associated in the way that they cause mild to severe upper respiratory tract illness. This study has used an unbiased analysis of publicly available gene expression datasets from Gene Expression Omnibus to understand the shared and unique transcriptional signatures of human lung epithelial cells infected with SARS-CoV-2 relative to MERS-CoV or SARS-CoV. A major goal was to discover unique cellular responses to SARS-CoV-2 among these three coronaviruses. Analyzing differentially expressed genes (DEGs) shared by the three datasets led to a set of 17 genes, suggesting the lower expression of genes related to acute inflammatory response (TNF, IL32, IL1A, CXCL1, and CXCL3) in SARS-CoV-2. This subdued transcriptional response to SARS-CoV-2 may cause prolonged viral replication, leading to severe lung damage. Downstream analysis of unique DEGs of SARS-CoV-2 infection revealed changes in genes related to apoptosis (NRP1, FOXO1, TP53INP1, CSF2, and NLRP1), coagulation (F3, PROS1, ITGB3, and TFPI2), and vascular function (VAV3, TYMP, TCF4, and NR2F2), which may contribute to more systemic cardiovascular complications of COVID-19 than MERS and SARS. The study has uncovered a novel set of transcriptomic signatures unique to SARS-CoV-2 infection and shared by three coronaviruses, which may guide the initial efforts in the development of prognostic or therapeutic tools for COVID-19.

【 授权许可】

CC BY