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

2020; Elsevier BV; Volume: 85; Linguagem: Inglês

10.1016/j.meegid.2020.104438

1567-7257

Hsin-Liang Liu, I‐Jeng Yeh, Nam Nhut Phan, Yen‐Hung Wu, Meng‐Chi Yen, Jui‐Hsiang Hung, Chung-Chieh Chiao, Chien‐Fu Chen, Zhengda Sun, Jiazhen Jiang, Hui‐Ping Hsu, Chih‐Yang Wang, Ming‐Derg Lai,

Extracellular vesicles in disease

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.