Comparative pathogenesis of Ebola virus and Reston virus infection in humanized mice

Escudero-Pérez, Beatriz; Ruibal, Paula; Rottstegge, Monika; Lüdtke, Anja; Port, Julia R; Hartmann, Kristin; Gómez‐Medina, Sergio; Müller-Guhl, Jürgen; Nelson, Emily V; Krasemann, Susanne; Rodríguez, Estefanía; Muñoz‐Fontela, César

doi:10.1172/jci.insight.126070

Cited by 29 publications

(38 citation statements)

References 44 publications

(60 reference statements)

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“…More recently, laboratory mice seeded with human immune, liver, and thymus cells supported virus replication leading to lethal disease. However, some variation in disease severity was noted between mice with different human cell donors [ 10 , 11 ]. Domestic ferrets are permissive to infection and exhibit many signs of human EVD including rash and gastrointestinal signs [ 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Kikwit Ebola Virus Disease Progression in the Rhesus Monkey Animal Model

Bennett

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Zlobec

et al. 2020

Viruses

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Ongoing Ebola virus disease outbreaks in the Democratic Republic of the Congo follow the largest recorded outbreak in Western Africa (2013–2016). To combat outbreaks, testing of medical countermeasures (therapeutics or vaccines) requires a well-defined, reproducible, animal model. Here we present Ebola virus disease kinetics in 24 Chinese-origin rhesus monkeys exposed intramuscularly to a highly characterized, commercially available Kikwit Ebola virus Filovirus Animal Non-Clinical Group (FANG) stock. Until reaching predetermined clinical disease endpoint criteria, six animals underwent anesthesia for repeated clinical sampling and were compared to six that did not. Groups of three animals were euthanized and necropsied on days 3, 4, 5, and 6 post-exposure, respectively. In addition, three uninfected animals served as controls. Here, we present detailed characterization of clinical and laboratory disease kinetics and complete blood counts, serum chemistries, Ebola virus titers, and disease kinetics for future medical countermeasure (MCM) study design and control data. We measured no statistical difference in hematology, chemistry values, or time to clinical endpoint in animals that were anesthetized for clinical sampling during the acute disease compared to those that were not.

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Section: Introductionmentioning

confidence: 99%

Kikwit Ebola Virus Disease Progression in the Rhesus Monkey Animal Model

Bennett

Logue

Zlobec

et al. 2020

Viruses

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Section: Ebolavirusesmentioning

confidence: 91%

“…EBOV isolated from the more recent West Africa outbreak (Makona strain) can also induce a lethal outcome in hu-NSG-A2 mice, but only to a limited extent [37]. When other species of ebolaviruses were evaluated in hu-NSG-A2 mice, SUDV, RESTV, TAFV, and BDBV all caused lower lethality rates than EBOV [37], reflecting relative case-fatality rates reported for the respective species in human cases. However, while only non-pathogenic human RESTV infections have been recorded [59], RESTV caused a 20% lethality rate in hu-NSG-A2 mice, a rate previously exceeded only in infected NHPs [60,61].…”

Section: Ebolavirusesmentioning

confidence: 91%

“…The human cell-engrafted NOD.Cg-Prkdc scid Il2rg tm1Wjl Tg (HLA-A2.1) 1Enge/Sz mice (hu-NSG-A2) that express human HLA-A2 provided the first platform for a lethal EBOV mouse model without the need of prior virus adaption to the host [38]. Lethal disease is observed in hu-NSG-A2 following intraperitoneal [58] or intranasal inoculation with the prototypic EBOV Mayinga strain [37].…”

Section: Ebolavirusesmentioning

confidence: 99%

“…This is not unexpected, as the human immune features of each specific HIS model influence the disease process. For example, CTL-mediated pathogenesis has been observed in the hu-NSG-A2 model of EBOV [37] resulting in liver pathology. This is due to the expression of HLA-A2-restricted epitopes that can be presented by infected murine cells and targeted by human CTLs.…”

Section: What We Have Learned About Using His Mice For Vhf Studiesmentioning

confidence: 99%

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The Utility of Human Immune System Mice for High-Containment Viral Hemorrhagic Fever Research

et al. 2020

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Human immune system (HIS) mice are a subset of humanized mice that are generated by xenoengraftment of human immune cells or tissues and/or their progenitors into immunodeficient mice. Viral hemorrhagic fevers (VHFs) cause severe disease in humans, typically with high case fatality rates. HIS mouse studies have been performed to investigate the pathogenesis and immune responses to VHFs that must be handled in high-containment laboratory facilities. Here, we summarize studies on filoviruses, nairoviruses, phenuiviruses, and hantaviruses, and discuss the knowledge gained from using various HIS mouse models. Furthermore, we discuss the complexities of designing and interpreting studies utilizing HIS mice while highlighting additional questions about VHFs that can still be addressed using HIS mouse models.

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Orthotopic PDX and CDX Mice Model for Cancer Stem Cell Research

Das

2022

Handbook of Animal Models and Its Uses in Cancer Research

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Comparative pathogenesis of Ebola virus and Reston virus infection in humanized mice

Cited by 29 publications

References 44 publications

Kikwit Ebola Virus Disease Progression in the Rhesus Monkey Animal Model

Kikwit Ebola Virus Disease Progression in the Rhesus Monkey Animal Model

The Utility of Human Immune System Mice for High-Containment Viral Hemorrhagic Fever Research

Orthotopic PDX and CDX Mice Model for Cancer Stem Cell Research

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