Abstract
Interferon gamma (IFN-γ) may be potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-γ pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2-positive and -negative patients, we identified IFN-γ-associated pathways to be enriched in positive patients. Bioinformatics analyses showed upregulation of MAP2K6 , CBL , RUNX3 , STAT1 , and JAK2 in COVID-19-positive vs. -negative patients. A positive correlation was observed between STAT1 / JAK2 , which varied alongside the patient’s viral load. Expression of MX1 , MX2 , ISG15 , and OAS1 (four well-known IFN-stimulated genes (ISGs)) displayed upregulation in COVID-19-positive vs. -negative patients. Integrative analyses showcased higher levels of ISGs, which were associated with increased viral load and STAT1 / JAK2 expression. Confirmation of ISGs up-regulation was performed in vitro using the A549 lung cell line treated with Poly (I:C), a synthetic analog of viral double-stranded RNA; and in different pulmonary human cell lines and ferret tracheal biopsies infected with SARS-CoV-2. A pre-clinical murine model of Coronavirus infection confirmed findings displaying increased ISGs in the liver and lungs from infected mice. Altogether, these results demonstrate the role of IFN-γ and ISGs in response to SARS-CoV-2 infection, highlighting alternative druggable targets that can boost the host response.
Keywords: COVID-19; IFN-γ; ISGs.
【저자키워드】 COVID-19, IFN-γ, ISGs., 【초록키워드】 OAS1, Immunotherapy, SARS-COV-2 infection, Infection, lung, host response, in vitro, Viral load, mice, pathway, target, murine model, Stat1, expression, liver, patients, ISGs, COVID-19 patients, boost, ISG, case-control study, A549, ISG15, biopsy, confirmation, positive correlation, positive patients, upregulation, JAK2, gene expression profile, lung cell, the patient, was performed, treated, analysis, tracheal, displaying, IFN-stimulated gene, double-stranded, highlighting, CBL, human cell line, infected with SARS-CoV-2, MAP2K6, MX1, MX2, RUNX3, 【제목키워드】 SARS-CoV-2, Hub, Responding,