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Gene signatures of SARS-CoV/SARS-CoV-2-infected ferret lungs in short- and long-term models

Authors :
Meng-Chi Yen
Ming Derg Lai
Chih-Yang Wang
Hui Ping Hsu
I-Jeng Yeh
Jui-Hsiang Hung
Zhengda Sun
Chien Fu Chen
Nam Nhut Phan
Hsin-Liang Liu
Jia-Zhen Jiang
Yen-Hung Wu
Chung-Chieh Chiao
Source :
Infection, Genetics and Evolution
Publication Year :
2020
Publisher :
Elsevier B.V., 2020.

Abstract

Coronaviruses (CoVs) consist of six strains, and the severe acute respiratory syndrome coronavirus (SARS-CoV), newly found coronavirus (SARS-CoV-2) has rapidly spread leading to a global outbreak. The ferret (Mustela putorius furo) serves as a useful animal model for studying SARS-CoV/SARS-CoV-2 infection and developing therapeutic strategies. A holistic approach for distinguishing differences in gene signatures during disease progression is lacking. The present study discovered gene expression profiles of short-term (3 days) and long-term (14 days) ferret models after SARS-CoV/SARS-CoV-2 infection using a bioinformatics approach. Through Gene Ontology (GO) and MetaCore analyses, we found that the development of stemness signaling was related to short-term SARS-CoV/SARS-CoV-2 infection. In contrast, pathways involving extracellular matrix and immune responses were associated with long-term SARS-CoV/SARS-CoV-2 infection. Some highly expressed genes in both short- and long-term models played a crucial role in the progression of SARS-CoV/SARS-CoV-2 infection, including DPP4, BMP2, NFIA, AXIN2, DAAM1, ZNF608, ME1, MGLL, LGR4, ABHD6, and ACADM. Meanwhile, we revealed that metabolic, glucocorticoid, and reactive oxygen species-associated networks were enriched in both short- and long-term infection models. The present study showed alterations in gene expressions from short-term to long-term SARS-CoV/SARS-CoV-2 infection. The current result provides an explanation of the pathophysiology for post-infectious sequelae and potential targets for treatment.<br />Highlights • The development of Wnt and stemness signaling were related to short-term SARS-CoV/SARS-CoV-2 infection. • The extracellular matrix and immune response were associated with long-term SARS-CoV/SARS-CoV-2 infection. • Metabolic, glucocorticoid, and reactive oxygen species-associated networks were enriched in both short- and long-term SARS-CoV/SARS-CoV-2 infected models.

Details

Language :
English
ISSN :
15677257 and 15671348
Volume :
85
Database :
OpenAIRE
Journal :
Infection, Genetics and Evolution
Accession number :
edsair.doi.dedup.....05b79f30972bd0d62d1f9b5f0b887083