NRF2 Antioxidant Response and Interferon-Stimulated Genes Are Differentially Expressed in Respiratory-Syncytial-Virus- and Rhinovirus-Infected Hospitalized Children
Leonardo Sorrentino,
Walter Toscanelli,
Matteo Fracella,
Marta De Angelis,
Federica Frasca,
Carolina Scagnolari,
Laura Petrarca,
Raffaella Nenna,
Fabio Midulla,
Anna Teresa Palamara,
Lucia Nencioni,
Alessandra Pierangeli
Affiliations
Leonardo Sorrentino
Laboratory of Virology, Department of Molecular Medicine, Sapienza University, 00185 Rome, Italy
Walter Toscanelli
Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, 00185 Rome, Italy
Matteo Fracella
Laboratory of Virology, Department of Molecular Medicine, Sapienza University, 00185 Rome, Italy
Marta De Angelis
Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, 00185 Rome, Italy
Federica Frasca
Laboratory of Virology, Department of Molecular Medicine, Sapienza University, 00185 Rome, Italy
Carolina Scagnolari
Laboratory of Virology, Department of Molecular Medicine, Sapienza University, 00185 Rome, Italy
Laura Petrarca
Department of Maternal Infantile and Urological Sciences, Sapienza University, 00185 Rome, Italy
Raffaella Nenna
Department of Maternal Infantile and Urological Sciences, Sapienza University, 00185 Rome, Italy
Fabio Midulla
Department of Maternal Infantile and Urological Sciences, Sapienza University, 00185 Rome, Italy
Anna Teresa Palamara
Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, 00185 Rome, Italy
Lucia Nencioni
Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, 00185 Rome, Italy
Alessandra Pierangeli
Laboratory of Virology, Department of Molecular Medicine, Sapienza University, 00185 Rome, Italy
Respiratory diseases caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV) are frequent causes of the hospitalization of children; nonetheless, RSV is responsible for the most severe and life-threatening illnesses. Viral infection triggers an inflammatory response, activating interferon (IFN)-mediated responses, including IFN-stimulated genes (ISG) expression with antiviral and immunomodulatory activities. In parallel, the reactive oxygen species (ROS) production activates nuclear factor erythroid 2-related factor 2 (NRF2), whose antioxidant activity can reduce inflammation by interacting with the NF-kB pathway and the IFN response. To clarify how the interplay of IFN and NRF2 may impact on clinical severity, we enrolled children hospitalized for bronchiolitis and pneumonia, and measured gene expression of type-I and III IFNs, of several ISGs, of NRF2 and antioxidant-related genes, i.e., glucose-6-phosphate dehydrogenase (G6PD), heme oxygenase 1 (HO1), and NAD(P)H dehydrogenase [Quinone] 1 (NQO1) in RSV- (RSV-A N = 33 and RSV-B N = 30) and HRV (N = 22)-positive respiratory samples. NRF2 and HO1 expression is significantly elevated in children with HRV infection compared to RSV (p = 0.012 and p = 0.007, respectively), whereas ISG15 and ISG56 expression is higher in RSV-infected children (p = 0.016 and p = 0.049, respectively). Children admitted to a pediatric intensive care unit (PICU) had reduced NRF2 expression (p = 0.002). These data suggest, for the first time, that lower activation of the NRF2 antioxidant response in RSV-infected infants may contribute to bronchiolitis severity.
