Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection?
Increasing evidence highlights the importance of the antiviral activities of the type III interferons (IFNλs; IL-28A, IL-28B, IL29, and IFNλ4) in the intestine. However, many viruses have developed strategies to counteract these defense mechanisms by preventing the production of IFNs. Here we use in...
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MDPI AG
2021-01-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/1/105 |
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| author | Virginia M. Stone Emma E. Ringqvist Pär G. Larsson Erna Domsgen Ulrika Holmlund Eva Sverremark-Ekström Malin Flodström-Tullberg |
| author_facet | Virginia M. Stone Emma E. Ringqvist Pär G. Larsson Erna Domsgen Ulrika Holmlund Eva Sverremark-Ekström Malin Flodström-Tullberg |
| author_sort | Virginia M. Stone |
| collection | DOAJ |
| description | Increasing evidence highlights the importance of the antiviral activities of the type III interferons (IFNλs; IL-28A, IL-28B, IL29, and IFNλ4) in the intestine. However, many viruses have developed strategies to counteract these defense mechanisms by preventing the production of IFNs. Here we use infection models, a clinical virus isolate, and several molecular biology techniques to demonstrate that both type I and III IFNs induce an antiviral state and attenuate Coxsackievirus group B (CVB) replication in human intestinal epithelial cells (IECs). While treatment of IECs with a viral mimic (poly (I:C)) induced a robust expression of both type I and III IFNs, no such up-regulation was observed after CVB infection. The blunted IFN response was paralleled by a reduction in the abundance of proteins involved in the induction of interferon gene transcription, including TIR-domain-containing adapter-inducing interferon-β (TRIF), mitochondrial antiviral-signaling protein (MAVS), and the global protein translation initiator eukaryotic translation initiation factor 4G (eIF4G). Taken together, this study highlights a potent anti-Coxsackieviral effect of both type I and III IFNs in cells located at the primary site of infection. Furthermore, we show for the first time that the production of type I and III IFNs in IECs is blocked by CVBs. These findings suggest that CVBs evade the host immune response in order to successfully infect the intestine. |
| first_indexed | 2024-03-10T13:29:10Z |
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| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T13:29:10Z |
| publishDate | 2021-01-01 |
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| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-8b4bca70cf2f4db2825d18beea0e2cc42023-11-21T08:20:15ZengMDPI AGMicroorganisms2076-26072021-01-019110510.3390/microorganisms9010105Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection?Virginia M. Stone0Emma E. Ringqvist1Pär G. Larsson2Erna Domsgen3Ulrika Holmlund4Eva Sverremark-Ekström5Malin Flodström-Tullberg6Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 52 Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 52 Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 52 Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 52 Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 52 Stockholm, SwedenIncreasing evidence highlights the importance of the antiviral activities of the type III interferons (IFNλs; IL-28A, IL-28B, IL29, and IFNλ4) in the intestine. However, many viruses have developed strategies to counteract these defense mechanisms by preventing the production of IFNs. Here we use infection models, a clinical virus isolate, and several molecular biology techniques to demonstrate that both type I and III IFNs induce an antiviral state and attenuate Coxsackievirus group B (CVB) replication in human intestinal epithelial cells (IECs). While treatment of IECs with a viral mimic (poly (I:C)) induced a robust expression of both type I and III IFNs, no such up-regulation was observed after CVB infection. The blunted IFN response was paralleled by a reduction in the abundance of proteins involved in the induction of interferon gene transcription, including TIR-domain-containing adapter-inducing interferon-β (TRIF), mitochondrial antiviral-signaling protein (MAVS), and the global protein translation initiator eukaryotic translation initiation factor 4G (eIF4G). Taken together, this study highlights a potent anti-Coxsackieviral effect of both type I and III IFNs in cells located at the primary site of infection. Furthermore, we show for the first time that the production of type I and III IFNs in IECs is blocked by CVBs. These findings suggest that CVBs evade the host immune response in order to successfully infect the intestine.https://www.mdpi.com/2076-2607/9/1/105Coxsackievirus (CVB)enterovirus<i>IFIH1</i>immune evasioninnate immunityinterferon |
| spellingShingle | Virginia M. Stone Emma E. Ringqvist Pär G. Larsson Erna Domsgen Ulrika Holmlund Eva Sverremark-Ekström Malin Flodström-Tullberg Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection? Microorganisms Coxsackievirus (CVB) enterovirus <i>IFIH1</i> immune evasion innate immunity interferon |
| title | Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection? |
| title_full | Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection? |
| title_fullStr | Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection? |
| title_full_unstemmed | Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection? |
| title_short | Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection? |
| title_sort | inhibition of type iii interferon expression in intestinal epithelial cells a strategy used by coxsackie b virus to evade the host s innate immune response at the primary site of infection |
| topic | Coxsackievirus (CVB) enterovirus <i>IFIH1</i> immune evasion innate immunity interferon |
| url | https://www.mdpi.com/2076-2607/9/1/105 |
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