NRF2 Antioxidant Response and Interferon‐Stimulated Genes Are Differentially Expressed in SARS‐CoV‐2‐Positive Young Subjects
ABSTRACT Background Several respiratory viruses, including Severe Acute Respiratory Syndrome‐Coronavirus‐2 (SARS‐CoV‐2), suppress nuclear factor‐E2‐related factor‐2 (NRF2) antioxidant response, generating oxidative stress conditions to its advantage. NRF2 has also been reported to regulate the innat...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.70109 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832087045515771904 |
|---|---|
| author | Walter Toscanelli Matteo Fracella Marta De Angelis Carolina Scagnolari Leonardo Sorrentino Elena Piselli Maria Elena Marcocci Fabio Midulla Enrica Mancino Raffaella Nenna Laura Petrarca Anna Teresa Palamara Guido Antonelli Alessandra Pierangeli Lucia Nencioni |
| author_facet | Walter Toscanelli Matteo Fracella Marta De Angelis Carolina Scagnolari Leonardo Sorrentino Elena Piselli Maria Elena Marcocci Fabio Midulla Enrica Mancino Raffaella Nenna Laura Petrarca Anna Teresa Palamara Guido Antonelli Alessandra Pierangeli Lucia Nencioni |
| author_sort | Walter Toscanelli |
| collection | DOAJ |
| description | ABSTRACT Background Several respiratory viruses, including Severe Acute Respiratory Syndrome‐Coronavirus‐2 (SARS‐CoV‐2), suppress nuclear factor‐E2‐related factor‐2 (NRF2) antioxidant response, generating oxidative stress conditions to its advantage. NRF2 has also been reported to regulate the innate immune response through the inhibition of the interferon (IFN) pathway. However, its modulation in younger individuals and its correlation with the IFN response remain to be elucidated. Methods The NRF2 and redox‐related genes expression was examined in nasopharyngeal swabs from children attending the pediatric hospital for SARS‐CoV‐2 molecular testing. Expression levels were analyzed by stratifying the population according to the SARS‐CoV‐2 positivity, age, or the presence of symptoms. The results were correlated with Types I and III IFN genes and IFN‐stimulated genes (ISGs). Results We found that NRF2 expression was markedly diminished in positive patients compared to negative. Moreover, it correlated with higher expression of IFNα2 and IFNλ3, as well as ISG15 and ISG56. Interestingly, symptomatic patients with anosmia/ageusia showed pronounced expression of apurinic/apyrimidinic endonuclease1/redox factor 1 (APE1), together with Type I IFNs, ISG56, and the inflammasome component NLRP3. Conclusion The results indicate an interdependence between NRF2 antioxidant pathway and IFN‐mediated response during SARS‐CoV‐2 infection in young subjects. |
| format | Article |
| id | doaj-art-abafb24d0e03414796077471bff23c44 |
| institution | Kabale University |
| issn | 2050-4527 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj-art-abafb24d0e03414796077471bff23c442025-02-06T07:50:38ZengWileyImmunity, Inflammation and Disease2050-45272025-01-01131n/an/a10.1002/iid3.70109NRF2 Antioxidant Response and Interferon‐Stimulated Genes Are Differentially Expressed in SARS‐CoV‐2‐Positive Young SubjectsWalter Toscanelli0Matteo Fracella1Marta De Angelis2Carolina Scagnolari3Leonardo Sorrentino4Elena Piselli5Maria Elena Marcocci6Fabio Midulla7Enrica Mancino8Raffaella Nenna9Laura Petrarca10Anna Teresa Palamara11Guido Antonelli12Alessandra Pierangeli13Lucia Nencioni14Laboratory Affiliated to Istituto Pasteur Italia‐Fondazione Cenci Bolognetti, Department of Public Health and Infectious Diseases Sapienza University Rome ItalyLaboratory of Virology, Department of Molecular Medicine Sapienza University Rome ItalyLaboratory Affiliated to Istituto Pasteur Italia‐Fondazione Cenci Bolognetti, Department of Public Health and Infectious Diseases Sapienza University Rome ItalyLaboratory of Virology, Department of Molecular Medicine Sapienza University Rome ItalyLaboratory of Virology, Department of Molecular Medicine Sapienza University Rome ItalyLaboratory Affiliated to Istituto Pasteur Italia‐Fondazione Cenci Bolognetti, Department of Public Health and Infectious Diseases Sapienza University Rome ItalyLaboratory Affiliated to Istituto Pasteur Italia‐Fondazione Cenci Bolognetti, Department of Public Health and Infectious Diseases Sapienza University Rome ItalyDepartment of Maternal Infantile and Urological Sciences Sapienza University Rome ItalyDepartment of Maternal Infantile and Urological Sciences Sapienza University Rome ItalyDepartment of Maternal Infantile and Urological Sciences Sapienza University Rome ItalyDepartment of Maternal Infantile and Urological Sciences Sapienza University Rome ItalyLaboratory Affiliated to Istituto Pasteur Italia‐Fondazione Cenci Bolognetti, Department of Public Health and Infectious Diseases Sapienza University Rome ItalyLaboratory of Virology, Department of Molecular Medicine Sapienza University Rome ItalyLaboratory of Virology, Department of Molecular Medicine Sapienza University Rome ItalyLaboratory Affiliated to Istituto Pasteur Italia‐Fondazione Cenci Bolognetti, Department of Public Health and Infectious Diseases Sapienza University Rome ItalyABSTRACT Background Several respiratory viruses, including Severe Acute Respiratory Syndrome‐Coronavirus‐2 (SARS‐CoV‐2), suppress nuclear factor‐E2‐related factor‐2 (NRF2) antioxidant response, generating oxidative stress conditions to its advantage. NRF2 has also been reported to regulate the innate immune response through the inhibition of the interferon (IFN) pathway. However, its modulation in younger individuals and its correlation with the IFN response remain to be elucidated. Methods The NRF2 and redox‐related genes expression was examined in nasopharyngeal swabs from children attending the pediatric hospital for SARS‐CoV‐2 molecular testing. Expression levels were analyzed by stratifying the population according to the SARS‐CoV‐2 positivity, age, or the presence of symptoms. The results were correlated with Types I and III IFN genes and IFN‐stimulated genes (ISGs). Results We found that NRF2 expression was markedly diminished in positive patients compared to negative. Moreover, it correlated with higher expression of IFNα2 and IFNλ3, as well as ISG15 and ISG56. Interestingly, symptomatic patients with anosmia/ageusia showed pronounced expression of apurinic/apyrimidinic endonuclease1/redox factor 1 (APE1), together with Type I IFNs, ISG56, and the inflammasome component NLRP3. Conclusion The results indicate an interdependence between NRF2 antioxidant pathway and IFN‐mediated response during SARS‐CoV‐2 infection in young subjects.https://doi.org/10.1002/iid3.70109antioxidant responseAPE‐1inflammasomeInterferon responseNRF2SARS‐CoV‐2 |
| spellingShingle | Walter Toscanelli Matteo Fracella Marta De Angelis Carolina Scagnolari Leonardo Sorrentino Elena Piselli Maria Elena Marcocci Fabio Midulla Enrica Mancino Raffaella Nenna Laura Petrarca Anna Teresa Palamara Guido Antonelli Alessandra Pierangeli Lucia Nencioni NRF2 Antioxidant Response and Interferon‐Stimulated Genes Are Differentially Expressed in SARS‐CoV‐2‐Positive Young Subjects Immunity, Inflammation and Disease antioxidant response APE‐1 inflammasome Interferon response NRF2 SARS‐CoV‐2 |
| title | NRF2 Antioxidant Response and Interferon‐Stimulated Genes Are Differentially Expressed in SARS‐CoV‐2‐Positive Young Subjects |
| title_full | NRF2 Antioxidant Response and Interferon‐Stimulated Genes Are Differentially Expressed in SARS‐CoV‐2‐Positive Young Subjects |
| title_fullStr | NRF2 Antioxidant Response and Interferon‐Stimulated Genes Are Differentially Expressed in SARS‐CoV‐2‐Positive Young Subjects |
| title_full_unstemmed | NRF2 Antioxidant Response and Interferon‐Stimulated Genes Are Differentially Expressed in SARS‐CoV‐2‐Positive Young Subjects |
| title_short | NRF2 Antioxidant Response and Interferon‐Stimulated Genes Are Differentially Expressed in SARS‐CoV‐2‐Positive Young Subjects |
| title_sort | nrf2 antioxidant response and interferon stimulated genes are differentially expressed in sars cov 2 positive young subjects |
| topic | antioxidant response APE‐1 inflammasome Interferon response NRF2 SARS‐CoV‐2 |
| url | https://doi.org/10.1002/iid3.70109 |
| work_keys_str_mv | AT waltertoscanelli nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT matteofracella nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT martadeangelis nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT carolinascagnolari nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT leonardosorrentino nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT elenapiselli nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT mariaelenamarcocci nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT fabiomidulla nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT enricamancino nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT raffaellanenna nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT laurapetrarca nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT annateresapalamara nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT guidoantonelli nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT alessandrapierangeli nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects AT lucianencioni nrf2antioxidantresponseandinterferonstimulatedgenesaredifferentiallyexpressedinsarscov2positiveyoungsubjects |