ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation

Journal of Virology
Rubén González-SanzIsidoro Martínez

Abstract

Human respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infection in vitro. In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments, along with ISG15 knockout (ISG15(-/-)) cells, revealed an anti-RSV effect of the molecule. Conjugation inhibition assays demonstrated that ISG15 exerts its antiviral activity via protein ISGylation. This antiviral activity requires high levels of ISG15 to be present in the cells before RSV infection. Finally, ISG15 is also upregulated in human respiratory pseudostratified epithelia and in nasopharyngeal washes from infants infected with RSV, pointing to a possible antiviral role of the molecule in vivo. These results advance our understanding of the i...Continue Reading

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Citations

Dec 8, 2017·Viruses·Fernando Villalón-LetelierPatrick C Reading
Dec 14, 2017·Viruses·Esmeralda Magro-LopezAlberto Zambrano
May 12, 2018·Yonsei Medical Journal·Joo Heon YoonSeung Joon Baek
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Oct 12, 2017·Frontiers in Immunology·María Martín-VicenteIsidoro Martínez
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Dec 6, 2020·Viruses·Rubaiyea FarrukeePatrick C Reading
Jun 4, 2020·Virus Research·Brendan T FreitasScott D Pegan
May 11, 2021·Frontiers in Cell and Developmental Biology·Mounira K Chelbi-Alix, Pierre Thibault

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