Effect of Interferon Gamma on Ebola Virus Infection of Primary Kupffer Cells and a Kupffer Cell Line
Ebola virus disease (EVD) represents a global health threat. The etiological agents of EVD are six species of Orthoebolaviruses, with <i>Orthoebolavirus zairense</i> (EBOV) having the greatest public health and medical significance. EVD pathogenesis occurs as a result of broad cellular t...
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MDPI AG
2023-10-01
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| Online Access: | https://www.mdpi.com/1999-4915/15/10/2077 |
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| author | José A. Aguilar-Briseño Jonah M. Elliff Justin J. Patten Lindsay R. Wilson Robert A. Davey Adam L. Bailey Wendy J. Maury |
| author_facet | José A. Aguilar-Briseño Jonah M. Elliff Justin J. Patten Lindsay R. Wilson Robert A. Davey Adam L. Bailey Wendy J. Maury |
| author_sort | José A. Aguilar-Briseño |
| collection | DOAJ |
| description | Ebola virus disease (EVD) represents a global health threat. The etiological agents of EVD are six species of Orthoebolaviruses, with <i>Orthoebolavirus zairense</i> (EBOV) having the greatest public health and medical significance. EVD pathogenesis occurs as a result of broad cellular tropism of the virus, robust viral replication and a potent and dysregulated production of cytokines. In vivo, tissue macrophages are some of the earliest cells infected and contribute significantly to virus load and cytokine production. While EBOV is known to infect macrophages and to generate high titer virus in the liver, EBOV infection of liver macrophages, Kupffer cells, has not previously been examined in tissue culture or experimentally manipulated in vivo. Here, we employed primary murine Kupffer cells (KC) and an immortalized murine Kupffer cell line (ImKC) to assess EBOV-eGFP replication in liver macrophages. KCs and ImKCs were highly permissive for EBOV infection and IFN-γ polarization of these cells suppressed their permissiveness to infection. The kinetics of IFN-γ-elicited antiviral responses were examined using a biologically contained model of EBOV infection termed EBOV ΔVP30. The antiviral activity of IFN-γ was transient, but a modest ~3-fold reduction of infection persisted for as long as 6 days post-treatment. To assess the interferon-stimulated gene products (ISGs) responsible for protection, the efficacy of secreted ISGs induced by IFN-γ was evaluated and secreted ISGs failed to block EBOV ΔVP30. Our studies define new cellular tools for the study of EBOV infection that can potentially aid the development of new antiviral therapies. Furthermore, our data underscore the importance of macrophages in EVD pathogenesis and those IFN-γ-elicited ISGs that help to control EBOV infection. |
| first_indexed | 2024-03-10T20:50:02Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T20:50:02Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-8ec13b477aa54df5b528f517666708af2023-11-19T18:27:56ZengMDPI AGViruses1999-49152023-10-011510207710.3390/v15102077Effect of Interferon Gamma on Ebola Virus Infection of Primary Kupffer Cells and a Kupffer Cell LineJosé A. Aguilar-Briseño0Jonah M. Elliff1Justin J. Patten2Lindsay R. Wilson3Robert A. Davey4Adam L. Bailey5Wendy J. Maury6Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USAGraduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USADepartment of Virology, Immunology, and Microbiology, National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USADepartment of Virology, Immunology, and Microbiology, National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USADepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USAEbola virus disease (EVD) represents a global health threat. The etiological agents of EVD are six species of Orthoebolaviruses, with <i>Orthoebolavirus zairense</i> (EBOV) having the greatest public health and medical significance. EVD pathogenesis occurs as a result of broad cellular tropism of the virus, robust viral replication and a potent and dysregulated production of cytokines. In vivo, tissue macrophages are some of the earliest cells infected and contribute significantly to virus load and cytokine production. While EBOV is known to infect macrophages and to generate high titer virus in the liver, EBOV infection of liver macrophages, Kupffer cells, has not previously been examined in tissue culture or experimentally manipulated in vivo. Here, we employed primary murine Kupffer cells (KC) and an immortalized murine Kupffer cell line (ImKC) to assess EBOV-eGFP replication in liver macrophages. KCs and ImKCs were highly permissive for EBOV infection and IFN-γ polarization of these cells suppressed their permissiveness to infection. The kinetics of IFN-γ-elicited antiviral responses were examined using a biologically contained model of EBOV infection termed EBOV ΔVP30. The antiviral activity of IFN-γ was transient, but a modest ~3-fold reduction of infection persisted for as long as 6 days post-treatment. To assess the interferon-stimulated gene products (ISGs) responsible for protection, the efficacy of secreted ISGs induced by IFN-γ was evaluated and secreted ISGs failed to block EBOV ΔVP30. Our studies define new cellular tools for the study of EBOV infection that can potentially aid the development of new antiviral therapies. Furthermore, our data underscore the importance of macrophages in EVD pathogenesis and those IFN-γ-elicited ISGs that help to control EBOV infection.https://www.mdpi.com/1999-4915/15/10/2077macrophageKupffer cellinterferon gammaEbola virusfilovirus |
| spellingShingle | José A. Aguilar-Briseño Jonah M. Elliff Justin J. Patten Lindsay R. Wilson Robert A. Davey Adam L. Bailey Wendy J. Maury Effect of Interferon Gamma on Ebola Virus Infection of Primary Kupffer Cells and a Kupffer Cell Line Viruses macrophage Kupffer cell interferon gamma Ebola virus filovirus |
| title | Effect of Interferon Gamma on Ebola Virus Infection of Primary Kupffer Cells and a Kupffer Cell Line |
| title_full | Effect of Interferon Gamma on Ebola Virus Infection of Primary Kupffer Cells and a Kupffer Cell Line |
| title_fullStr | Effect of Interferon Gamma on Ebola Virus Infection of Primary Kupffer Cells and a Kupffer Cell Line |
| title_full_unstemmed | Effect of Interferon Gamma on Ebola Virus Infection of Primary Kupffer Cells and a Kupffer Cell Line |
| title_short | Effect of Interferon Gamma on Ebola Virus Infection of Primary Kupffer Cells and a Kupffer Cell Line |
| title_sort | effect of interferon gamma on ebola virus infection of primary kupffer cells and a kupffer cell line |
| topic | macrophage Kupffer cell interferon gamma Ebola virus filovirus |
| url | https://www.mdpi.com/1999-4915/15/10/2077 |
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