Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Ebola Virus Infection of Liver Cells: Effect of Interferon Gamma on Virus Infection of Primary Kupffer Cells and a Kupffer Cell Line

José A. Aguilar-Briseño
ORCID logo ,
Jonah M. Elliff
,
J. J. Patten
ORCID logo ,
Lindsay R. Wilson
ORCID logo ,
Robert A. Davey
,
Adam L. Bailey
,
Wendy J. Maury
* ORCID logo
Version 1 : Received: 28 August 2023 / Approved: 29 August 2023 / Online: 29 August 2023 (14:17:01 CEST)

A peer-reviewed article of this Preprint also exists.

Aguilar-Briseño, J.A.; Elliff, J.M.; Patten, J.J.; Wilson, L.R.; Davey, R.A.; Bailey, A.L.; Maury, W.J. Effect of Interferon Gamma on Ebola Virus Infection of Primary Kupffer Cells and a Kupffer Cell Line. Viruses 2023, 15, 2077. Aguilar-Briseño, J.A.; Elliff, J.M.; Patten, J.J.; Wilson, L.R.; Davey, R.A.; Bailey, A.L.; Maury, W.J. Effect of Interferon Gamma on Ebola Virus Infection of Primary Kupffer Cells and a Kupffer Cell Line. Viruses 2023, 15, 2077.

Abstract

Ebola virus disease (EVD) represents a global health threat. The etiological agents of EVD are 6 species of Orthoebolaviruses, with Orthoebolavirus zairense (EBOV) having the greatest public health and medical significance. EVD disease 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 were evaluated. Secreted ISGs blocked recombinant VSV expressing EBOV GP (rVSV/EBOV GP) infection, but 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.

Keywords

Macrophage; Kupffer cell; interferon gamma; Ebola virus; filovirus

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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