Artículo
Pin-Pointing the Key Hubs in the IFN-γ Pathway Responding to SARS-CoV-2 Infection
Toro, Ayelen Rayen
; Lage Vickers, Sofia
; Bizzotto, Juan Antonio; Vilicich, Felipe; Sabater, Agustina Ayelen
; Pascual, Gastón Mario; Ledesma Bazan, Paula Sabrina
; Sanchis, Pablo Antonio
; Ruiz, María Sol
; Arevalo, Ana Paula; Porfido, Jorge L.; Abbate, María Mercedes
; Seniuk, Rocio Alejandra; Labanca, Estefania; Anselmino, Nicolás
; Navone, Nora; Alonso, Daniel Fernando
; Vazquez, Elba Susana
; Crispo, Martina; Cotignola, Javier Hernan
; Gueron, Geraldine
Fecha de publicación:
09/2022
Editorial:
MDPI
Revista:
Viruses
ISSN:
1999-4915
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
COVID-19
,
IFN-Γ
,
ISGS
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Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Toro, Ayelen Rayen; Lage Vickers, Sofia; Bizzotto, Juan Antonio; Vilicich, Felipe; Sabater, Agustina Ayelen; et al.; Pin-Pointing the Key Hubs in the IFN-γ Pathway Responding to SARS-CoV-2 Infection; MDPI; Viruses; 14; 10; 9-2022; 1-22
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