Journal article
Interferons Inhibit Ebola Virus Infection of Human Keratinocytes
Viruses, Vol.17(12), 1577
01/01/2025
DOI: 10.3390/v17121577
PMCID: PMC12737376
PMID: 41472248
Abstract
Orthoebolavirus zairense is the species name for Zaire Ebola virus (EBOV) within Filoviridae. This group of viruses can cause severe disease in humans, characterized by hemorrhagic shock, coagulation abnormalities, and severe inflammation. While tissue macrophages are critical targets early during EBOV infection, other cell types support viral replication as disease progresses. At late stages of infection, infectious EBOV is found on the surface of the skin, which may be a critical source of infectious virus transmitted between individuals during outbreaks. Human skin contains a number of cellular targets of EBOV, including keratinocytes. Here, we demonstrate EBOV infection of telomerase-immortalized normal human skin keratinocytes (NHSK-1), as well as EBOVΔVP30 infection of NHSK-1 cells that were stably complemented with EBOV transcription factor VP30. Infection with EBOVΔVP30 did not elicit detectable endogenous interferon responses; however, exogenous pre-treatment of NHSK-1 cells with type I, II, and III interferon (IFN) inhibited EBOVΔVP30 infection and infection of an additional low-containment model of EBOV, rVSV/EBOV GP, in a dose-dependent manner. Analysis of the transcriptome of IFN-treated keratinocytes identified multiple genes unique to each IFN and a subset of ISGs upregulated by all three IFNs. Our results indicate that ISGs induced by IFN pre-treatment of keratinocytes can reduce infection, underlining that ISGs may serve as EBOV-targeting therapeutics.
Details
- Title: Subtitle
- Interferons Inhibit Ebola Virus Infection of Human Keratinocytes
- Creators
- Jonah ElliffHanora Van ErtKristina SevcikMarija Djurkovic - Texas Biomedical Research InstituteDanielle RuddFrançoise GourroncAloysius KlingelhutzOlena ShtankoWendy Maury
- Resource Type
- Journal article
- Publication Details
- Viruses, Vol.17(12), 1577
- DOI
- 10.3390/v17121577
- PMID
- 41472248
- PMCID
- PMC12737376
- NLM abbreviation
- Viruses
- ISSN
- 1999-4915
- eISSN
- 1999-4915
- Publisher
- MDPI AG; BASEL
- Grant note
- National Institutes of Health: R01AI134733, R21AI123616, R21AI154336, R21AI151717 NIH: T32AI007485, F30AI181340, T32GM007337, F30AI174686
This research was supported by National Institutes of Health (NIH, USA) grants R01AI134733 and R21AI123616 to W.M. and R21AI154336 and R21AI151717 to O.S. J.E. was supported by NIH T32AI007485 and F30AI181340. H.V.E. was supported by NIH T32AI007485, T32GM007337 and F30AI174686.
- Language
- English
- Date published
- 01/01/2025
- Academic Unit
- Microbiology and Immunology; Radiation Oncology
- Record Identifier
- 9985093886002771
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