BALANCING IMMUNE FORCES: EXPLORING IFN-γ YIN-YANG IN CORONAVIRUS DEFENSE

AGUSTINA SABATER; JUAN BIZZOTTO; GASTON PASCUAL; ANA PAULA AREVALO; MARIANOEL PEREIRA; JORGE PORFIDO; ROCIO SENIUK; INES ACHINELLI; PABLO SANCHIS; SOFIA LAGE VICKERS; ELBA VAZQUEZ; JAVIER COTIGNOLA; GONZALO MORATORIO; MARTINA CRISPO; GERALDINE GUERON; AYELEN TORO

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2023

Interferon gamma (IFN-γ) holds promise as a potential adjuvant immunotherapy for individuals with COVID-19. This study explored the gene expression patterns related to the IFN-γ pathway in reaction to Coronavirus infection. Through a case-control investigation involving samples of nasopharyngeal swabs of SARS-CoV-2-positive and -negative patients, we identified enriched IFN-γ-associated pathways among the positive cases. Bioinformatics analyses revealed an upregulation of key genes including MAP2K6, CBL, RUNX3, STAT1, and JAK2 in COVID-19-positive patients compared to non-COVID patients. Notably, a positive correlation emerged between STAT1 and JAK2, varying alongside the patient's viral load. Moreover, the expression of well-established IFN-stimulated genes (ISGs) such as MX1, MX2, ISG15, and OAS1 displayed significant upregulation in COVID-19-positive patients. Integrative analyses further demonstrated elevated ISGs levels associated with higher viral loads and increased STAT1/JAK2 expression. To validate these findings, we conducted in vitro experiments utilizing the A549 lung cell line treated with Poly (I:C), a synthetic double-stranded RNA analog, as well as bioinformatics analyses of transcriptomics data from pulmonary human cell lines and ferret tracheal biopsies infected with SARS-CoV-2. Consistent results were obtained from our pre-clinical murine model of Coronavirus infection where BALB/cJ mice were infected with Murine Hepatitis Virus (MHV-A59, 6000 PFU), showing heightened ISGs expression in the liver and lungs of infected mice. Additionally, we evaluated the expression of Type I IFN; however, we did not observe changes in Infa expression with MHV infection in liver, suggesting that ISGs upregulation is triggered by IFN-γ signaling. These results extend the current knowledge about the role of IFN-γ in Coronavirus infection and provide biological basis for new therapies.