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The Robust Restriction of Zika Virus by Type-I Interferon in A549 Cells Varies by Viral Lineage and Is Not Determined by IFITM3

Type-I interferon (IFN-I) is a major antiviral host response but its impact on Zika virus (ZIKV) replication is not well defined, particularly as it relates to different circulating strains. Interferon stimulated genes (ISGs) that inhibit ZIKV, such as IFITM3, have been identified largely using over...

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Autores principales: Gobillot, Theodore A., Humes, Daryl, Sharma, Amit, Kikawa, Caroline, Overbaugh, Julie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290589/
https://www.ncbi.nlm.nih.gov/pubmed/32370187
http://dx.doi.org/10.3390/v12050503
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author Gobillot, Theodore A.
Humes, Daryl
Sharma, Amit
Kikawa, Caroline
Overbaugh, Julie
author_facet Gobillot, Theodore A.
Humes, Daryl
Sharma, Amit
Kikawa, Caroline
Overbaugh, Julie
author_sort Gobillot, Theodore A.
collection PubMed
description Type-I interferon (IFN-I) is a major antiviral host response but its impact on Zika virus (ZIKV) replication is not well defined, particularly as it relates to different circulating strains. Interferon stimulated genes (ISGs) that inhibit ZIKV, such as IFITM3, have been identified largely using overexpression studies. Here, we tested whether diverse ZIKV strains differed in their susceptibility to IFN-I-mediated restriction and the contribution of IFITM3 to this restriction. We identified a robust IFN-I-mediated antiviral effect on ZIKV replication (>100-fold reduction) in A549 cells, a commonly used cell line to study ZIKV replication. The extent of inhibition depended on the IFN-I type and the virus strain tested. Viruses from the American pathogenic outbreak were more sensitive to IFNα (p = 0.049) and IFNβ (p = 0.09) than African-lineage strains, which have not been linked to severe pathogenesis. Knocking out IFITM3 expression did not dampen the IFN-I antiviral effect and only high overexpression of IFITM3 led to ZIKV inhibition. Moreover, IFITM3 expression levels in different cells were not associated with IFN-mediated ZIKV inhibition. Taken together, our findings indicate that there is a robust IFN-I-mediated antiviral effect on ZIKV infection, particularly for American viruses, that is not due to IFITM3. A549 cells, which are a commonly used cell line to study ZIKV replication, present an opportunity for the discovery of novel antiviral ISGs against ZIKV.
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spelling pubmed-72905892020-06-17 The Robust Restriction of Zika Virus by Type-I Interferon in A549 Cells Varies by Viral Lineage and Is Not Determined by IFITM3 Gobillot, Theodore A. Humes, Daryl Sharma, Amit Kikawa, Caroline Overbaugh, Julie Viruses Article Type-I interferon (IFN-I) is a major antiviral host response but its impact on Zika virus (ZIKV) replication is not well defined, particularly as it relates to different circulating strains. Interferon stimulated genes (ISGs) that inhibit ZIKV, such as IFITM3, have been identified largely using overexpression studies. Here, we tested whether diverse ZIKV strains differed in their susceptibility to IFN-I-mediated restriction and the contribution of IFITM3 to this restriction. We identified a robust IFN-I-mediated antiviral effect on ZIKV replication (>100-fold reduction) in A549 cells, a commonly used cell line to study ZIKV replication. The extent of inhibition depended on the IFN-I type and the virus strain tested. Viruses from the American pathogenic outbreak were more sensitive to IFNα (p = 0.049) and IFNβ (p = 0.09) than African-lineage strains, which have not been linked to severe pathogenesis. Knocking out IFITM3 expression did not dampen the IFN-I antiviral effect and only high overexpression of IFITM3 led to ZIKV inhibition. Moreover, IFITM3 expression levels in different cells were not associated with IFN-mediated ZIKV inhibition. Taken together, our findings indicate that there is a robust IFN-I-mediated antiviral effect on ZIKV infection, particularly for American viruses, that is not due to IFITM3. A549 cells, which are a commonly used cell line to study ZIKV replication, present an opportunity for the discovery of novel antiviral ISGs against ZIKV. MDPI 2020-05-02 /pmc/articles/PMC7290589/ /pubmed/32370187 http://dx.doi.org/10.3390/v12050503 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gobillot, Theodore A.
Humes, Daryl
Sharma, Amit
Kikawa, Caroline
Overbaugh, Julie
The Robust Restriction of Zika Virus by Type-I Interferon in A549 Cells Varies by Viral Lineage and Is Not Determined by IFITM3
title The Robust Restriction of Zika Virus by Type-I Interferon in A549 Cells Varies by Viral Lineage and Is Not Determined by IFITM3
title_full The Robust Restriction of Zika Virus by Type-I Interferon in A549 Cells Varies by Viral Lineage and Is Not Determined by IFITM3
title_fullStr The Robust Restriction of Zika Virus by Type-I Interferon in A549 Cells Varies by Viral Lineage and Is Not Determined by IFITM3
title_full_unstemmed The Robust Restriction of Zika Virus by Type-I Interferon in A549 Cells Varies by Viral Lineage and Is Not Determined by IFITM3
title_short The Robust Restriction of Zika Virus by Type-I Interferon in A549 Cells Varies by Viral Lineage and Is Not Determined by IFITM3
title_sort robust restriction of zika virus by type-i interferon in a549 cells varies by viral lineage and is not determined by ifitm3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290589/
https://www.ncbi.nlm.nih.gov/pubmed/32370187
http://dx.doi.org/10.3390/v12050503
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