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How Different Pathologies Are Affected by IFIT Expression

The type-I interferon (IFN) system represents the first line of defense against viral pathogens. Recognition of the virus initiates complex signaling pathways that result in the transcriptional induction of IFNs, which are then secreted. Secreted IFNs stimulate nearby cells and result in the product...

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Autores principales: Franco, Justin H., Chattopadhyay, Saurabh, Pan, Zhixing K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963598/
https://www.ncbi.nlm.nih.gov/pubmed/36851555
http://dx.doi.org/10.3390/v15020342
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author Franco, Justin H.
Chattopadhyay, Saurabh
Pan, Zhixing K.
author_facet Franco, Justin H.
Chattopadhyay, Saurabh
Pan, Zhixing K.
author_sort Franco, Justin H.
collection PubMed
description The type-I interferon (IFN) system represents the first line of defense against viral pathogens. Recognition of the virus initiates complex signaling pathways that result in the transcriptional induction of IFNs, which are then secreted. Secreted IFNs stimulate nearby cells and result in the production of numerous proinflammatory cytokines and antiviral factors. Of particular note, IFN-induced tetratricopeptide repeat (IFIT) proteins have been thoroughly studied because of their antiviral activity against different viral pathogens. Although classically studied as an antiviral protein, IFIT expression has recently been investigated in the context of nonviral pathologies, such as cancer and sepsis. In oral squamous cell carcinoma (OSCC), IFIT1 and IFIT3 promote metastasis, while IFIT2 exhibits the opposite effect. The role of IFIT proteins during bacterial/fungal sepsis is still under investigation, with studies showing conflicting roles for IFIT2 in disease severity. In the setting of viral sepsis, IFIT proteins play a key role in clearing viral infection. As a result, many viral pathogens, such as SARS-CoV-2, employ mechanisms to inhibit the type-I IFN system and promote viral replication. In cancers that are characterized by upregulated IFIT proteins, medications that decrease IFIT expression may reduce metastasis and improve survival rates. Likewise, in cases of viral sepsis, therapeutics that increase IFIT expression may improve viral clearance and reduce the risk of septic shock. By understanding the effect of IFIT proteins in different pathologies, novel therapeutics can be developed to halt disease progression.
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spelling pubmed-99635982023-02-26 How Different Pathologies Are Affected by IFIT Expression Franco, Justin H. Chattopadhyay, Saurabh Pan, Zhixing K. Viruses Review The type-I interferon (IFN) system represents the first line of defense against viral pathogens. Recognition of the virus initiates complex signaling pathways that result in the transcriptional induction of IFNs, which are then secreted. Secreted IFNs stimulate nearby cells and result in the production of numerous proinflammatory cytokines and antiviral factors. Of particular note, IFN-induced tetratricopeptide repeat (IFIT) proteins have been thoroughly studied because of their antiviral activity against different viral pathogens. Although classically studied as an antiviral protein, IFIT expression has recently been investigated in the context of nonviral pathologies, such as cancer and sepsis. In oral squamous cell carcinoma (OSCC), IFIT1 and IFIT3 promote metastasis, while IFIT2 exhibits the opposite effect. The role of IFIT proteins during bacterial/fungal sepsis is still under investigation, with studies showing conflicting roles for IFIT2 in disease severity. In the setting of viral sepsis, IFIT proteins play a key role in clearing viral infection. As a result, many viral pathogens, such as SARS-CoV-2, employ mechanisms to inhibit the type-I IFN system and promote viral replication. In cancers that are characterized by upregulated IFIT proteins, medications that decrease IFIT expression may reduce metastasis and improve survival rates. Likewise, in cases of viral sepsis, therapeutics that increase IFIT expression may improve viral clearance and reduce the risk of septic shock. By understanding the effect of IFIT proteins in different pathologies, novel therapeutics can be developed to halt disease progression. MDPI 2023-01-25 /pmc/articles/PMC9963598/ /pubmed/36851555 http://dx.doi.org/10.3390/v15020342 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Franco, Justin H.
Chattopadhyay, Saurabh
Pan, Zhixing K.
How Different Pathologies Are Affected by IFIT Expression
title How Different Pathologies Are Affected by IFIT Expression
title_full How Different Pathologies Are Affected by IFIT Expression
title_fullStr How Different Pathologies Are Affected by IFIT Expression
title_full_unstemmed How Different Pathologies Are Affected by IFIT Expression
title_short How Different Pathologies Are Affected by IFIT Expression
title_sort how different pathologies are affected by ifit expression
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963598/
https://www.ncbi.nlm.nih.gov/pubmed/36851555
http://dx.doi.org/10.3390/v15020342
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