scholarly journals Mucosal Challenge Ferret Models of Ebola Virus Disease

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 292
Author(s):  
Trevor Brasel ◽  
Jason E. Comer ◽  
Shane Massey ◽  
Jeanon Smith ◽  
Jennifer Smith ◽  
...  
Keyword(s):  
Disease Progression ◽  
Intranasal Administration ◽  
Ebola Virus ◽  
Advanced Disease ◽  
Virus Disease ◽  
Small Animal ◽  
Clinical Pathology ◽  
Small Animal Model ◽  
Post Challenge ◽  
Mustela Putorius

Recent studies have shown the domestic ferret (Mustela putorius furo) to be a promising small animal model for the study of Ebola virus (EBOV) disease and medical countermeasure evaluation. To date, most studies have focused on traditional challenge routes, predominantly intramuscular and intranasal administration. Here, we present results from a non-clinical pathogenicity study examining oronasal, oral, and ocular mucosal challenge routes in ferrets. Animals were challenged with 1, 10, or 100 plaque forming units EBOV followed by monitoring of disease progression and biosampling. Ferrets administered virus via oronasal and oral routes met euthanasia criteria due to advanced disease 5–10 days post-challenge. Conversely, all ferrets dosed via the ocular route survived until the scheduled study termination 28-day post-challenge. In animals that succumbed to disease, a dose/route response was not observed; increases in disease severity, febrile responses, serum and tissue viral load, alterations in clinical pathology, and gross/histopathology findings were similar between subjects. Disease progression in ferrets challenged via ocular administration was unremarkable throughout the study period. Results from this study further support the ferret as a model for EBOV disease following oral and nasal mucosa exposure.

scholarly journals Ebola Virus Disease in Mice with Transplanted Human Hematopoietic Stem Cells

2015 ◽  
Vol 89 (8) ◽  
pp. 4700-4704 ◽  
Author(s):  
Anja Lüdtke ◽  
Lisa Oestereich ◽  
Paula Ruibal ◽  
Stephanie Wurr ◽  
Elisa Pallasch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ebola Virus ◽  
Virus Disease ◽  
Cell Damage ◽  
Liver Steatosis ◽  
Small Animal ◽  
Ebola Virus Disease ◽  
Small Animal Model ◽  
Hematopoietic Stem ◽  
Small Animal Models

The development of treatments for Ebola virus disease (EVD) has been hampered by the lack of small-animal models that mimick human disease. Here we show that mice with transplanted human hematopoetic stem cells reproduce features typical of EVD. Infection with Ebola virus was associated with viremia, cell damage, liver steatosis, signs of hemorrhage, and high lethality. Our study provides a small-animal model with human components for the development of EVD therapies.

scholarly journals Ferrets Infected with Bundibugyo Virus or Ebola Virus Recapitulate Important Aspects of Human Filovirus Disease

2016 ◽  
Vol 90 (20) ◽  
pp. 9209-9223 ◽  
Author(s):  
Robert Kozak ◽  
Shihua He ◽  
Andrea Kroeker ◽  
Marc-Antoine de La Vega ◽  
Jonathan Audet ◽  
...  
Keyword(s):  
Animal Model ◽  
Ebola Virus ◽  
Virus Transmission ◽  
Case Fatality ◽  
Small Animal ◽  
Hemorrhagic Fever ◽  
Transmission Model ◽  
Global Public Health ◽  
Small Animal Model ◽  
Content Type

ABSTRACTBundibugyo virus (BDBV) is the etiological agent of a severe hemorrhagic fever in humans with a case-fatality rate ranging from 25 to 36%. Despite having been known to the scientific and medical communities for almost 1 decade, there is a dearth of studies on this pathogen due to the lack of a small animal model. Domestic ferrets are commonly used to study other RNA viruses, including members of the orderMononegavirales. To investigate whether ferrets were susceptible to filovirus infections, ferrets were challenged with a clinical isolate of BDBV. Animals became viremic within 4 days and succumbed to infection between 8 and 9 days, and a petechial rash was observed with moribund ferrets. Furthermore, several hallmarks of human filoviral disease were recapitulated in the ferret model, including substantial decreases in lymphocyte and platelet counts and dysregulation of key biochemical markers related to hepatic/renal function, as well as coagulation abnormalities. Virological, histopathological, and immunohistochemical analyses confirmed uncontrolled BDBV replication in the major organs. Ferrets were also infected with Ebola virus (EBOV) to confirm their susceptibility to another filovirus species and to potentially establish a virus transmission model. Similar to what was seen with BDBV, important hallmarks of human filoviral disease were observed in EBOV-infected ferrets. This study demonstrates the potential of this small animal model for studying BDBV and EBOV using wild-type isolates and will accelerate efforts to understand filovirus pathogenesis and transmission as well as the development of specific vaccines and antivirals.IMPORTANCEThe 2013-2016 outbreak of Ebola virus in West Africa has highlighted the threat posed by filoviruses to global public health. Bundibugyo virus (BDBV) is a member of the genusEbolavirusand has caused outbreaks in the past but is relatively understudied, likely due to the lack of a suitable small animal model. Such a model for BDBV is crucial to evaluating vaccines and therapies and potentially understanding transmission. To address this, we demonstrated that ferrets are susceptible models to BDBV infection as well as to Ebola virus infection and that no virus adaptation is required. Moreover, these animals develop a disease that is similar to that seen in humans and nonhuman primates. We believe that this will improve the ability to study BDBV and provide a platform to test vaccines and therapeutics.

scholarly journals Development of a Well-Characterized Rhesus Macaque Model of Ebola Virus Disease for Support of Product Development

2021 ◽  
Vol 9 (3) ◽  
pp. 489
Author(s):  
Kendra J. Alfson ◽  
Yenny Goez-Gazi ◽  
Michal Gazi ◽  
Hilary Staples ◽  
Marc Mattix ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Ebola Virus ◽  
Virus Disease ◽  
Rna Virus ◽  
Rhesus Macaques ◽  
Systemic Disease ◽  
Clinical Pathology ◽  
Macaque Model ◽  
Progression Of Disease ◽  
Ebov Infection

Ebola virus (EBOV) is a negative-sense RNA virus that can infect humans and nonhuman primates with severe health consequences. Development of countermeasures requires a thorough understanding of the interaction between host and pathogen, and the course of disease. The goal of this study was to further characterize EBOV disease in a uniformly lethal rhesus macaque model, in order to support development of a well-characterized model following rigorous quality standards. Rhesus macaques were intramuscularly exposed to EBOV and one group was euthanized at predetermined time points to characterize progression of disease. A second group was not scheduled for euthanasia in order to analyze survival, changes in physiology, clinical pathology, terminal pathology, and telemetry kinetics. On day 3, sporadic viremia was observed and pathological evidence was noted in lymph nodes. By day 5, viremia was detected in all EBOV exposed animals and pathological evidence was noted in the liver, spleen, and gastrointestinal tissues. These data support the notion that EBOV infection in rhesus macaques is a rapid systemic disease similar to infection in humans, under a compressed time scale. Biomarkers that correlated with disease progression at the earliest stages of infection were observed thereby identifying potential “trigger-to-treat” for use in therapeutic studies.

scholarly journals In Vivo Replication and Pathogenesis of Vesicular Stomatitis Virus Recombinant M40 Containing Ebola Virus L-Domain Sequences

2012 ◽  
Vol 5 ◽  
pp. IDRT.S10652
Author(s):  
Takashi Irie ◽  
Elena Carnero ◽  
Adolfo García-Sastre ◽  
Ronald N. Harty
Keyword(s):  
Cell Culture ◽  
Animal Model ◽  
Vesicular Stomatitis Virus ◽  
Ebola Virus ◽  
Small Animal ◽  
Small Animal Model ◽  
Virus Recombinant ◽  
Vesicular Stomatitis ◽  
Ptap Motif

The M40 VSV recombinant was engineered to contain overlapping PTAP and PPxY L-domain motifs and flanking residues from the VP40 protein of Ebola virus. Replication of M40 in cell culture is virtually indistinguishable from that of control viruses. However, the presence of the Ebola PTAP motif in the M40 recombinant enabled this virus to interact with and recruit host Tsg101, which was packaged into M40 virions. In this brief report, we compared replication and the pathogenic profiles of M40 and the parental virus M51R in mice to determine whether the presence of the Ebola L-domains and flanking residues altered in vivo characteristics of the virus. Overall, the in vivo characteristics of M40 were similar to those of the parental M51R virus, indicating that the Ebola sequences did not alter pathogenesis of VSV in this small animal model of infection.

scholarly journals Filovirus Virulence in Interferon α/β and γ Double Knockout Mice, and Treatment with Favipiravir

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 137 ◽  
Author(s):  
Jason Comer ◽  
Olivier Escaffre ◽  
Natasha Neef ◽  
Trevor Brasel ◽  
Terry Juelich ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Ebola Virus ◽  
Virus Disease ◽  
Small Animal ◽  
Interferon Α ◽  
Wild Type ◽  
Early Screening ◽  
Double Knockout ◽  
Histological Changes

The 2014 Ebolavirus outbreak in West Africa highlighted the need for vaccines and therapeutics to prevent and treat filovirus infections. A well-characterized small animal model that is susceptible to wild-type filoviruses would facilitate the screening of anti-filovirus agents. To that end, we characterized knockout mice lacking α/β and γ interferon receptors (IFNAGR KO) as a model for wild-type filovirus infection. Intraperitoneal challenge of IFNAGR KO mice with several known human pathogenic species from the genus Ebolavirus and Marburgvirus, except Bundibugyo ebolavirus and Taï Forest ebolavirus, caused variable mortality rate. Further characterization of the prototype Ebola virus Kikwit isolate infection in this KO mouse model showed 100% lethality down to a dilution equivalent to 1.0 × 10−1 pfu with all deaths occurring between 7 and 9 days post-challenge. Viral RNA was detectable in serum after challenge with 1.0 × 102 pfu as early as one day after infection. Changes in hematology and serum chemistry became pronounced as the disease progressed and mirrored the histological changes in the spleen and liver that were also consistent with those described for patients with Ebola virus disease. In a proof-of-principle study, treatment of Ebola virus infected IFNAGR KO mice with favipiravir resulted in 83% protection. Taken together, the data suggest that IFNAGR KO mice may be a useful model for early screening of anti-filovirus medical countermeasures.

scholarly journals Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model

2014 ◽  
Vol 105 ◽  
pp. 17-21 ◽  
Author(s):  
Lisa Oestereich ◽  
Anja Lüdtke ◽  
Stephanie Wurr ◽  
Toni Rieger ◽  
César Muñoz-Fontela ◽  
...  
Keyword(s):  
Animal Model ◽  
Virus Infection ◽  
Successful Treatment ◽  
Ebola Virus ◽  
Small Animal ◽  
Small Animal Model ◽  
Ebola Virus Infection

scholarly journals Remdesivir is efficacious in rhesus monkeys exposed to aerosolized Ebola virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Travis K. Warren ◽  
Christopher D. Kane ◽  
Jay Wells ◽  
Kelly S. Stuthman ◽  
Sean A. Van Tongeren ◽  
...  
Keyword(s):  
Rhesus Monkeys ◽  
Ebola Virus ◽  
Virus Disease ◽  
Clinical Pathology ◽  
Ebola Virus Disease ◽  
Lymphoid Tissues ◽  
Virus Infections ◽  
Significant Survival ◽  
Blinded Study ◽  
Vehicle Treatment

AbstractEfficacious therapeutics for Ebola virus disease are in great demand. Ebola virus infections mediated by mucosal exposure, and aerosolization in particular, present a novel challenge due to nontypical massive early infection of respiratory lymphoid tissues. We performed a randomized and blinded study to compare outcomes from vehicle-treated and remdesivir-treated rhesus monkeys in a lethal model of infection resulting from aerosolized Ebola virus exposure. Remdesivir treatment initiated 4 days after exposure was associated with a significant survival benefit, significant reduction in serum viral titer, and improvements in clinical pathology biomarker levels and lung histology compared to vehicle treatment. These observations indicate that remdesivir may have value in countering aerosol-induced Ebola virus disease.

Treatment of ebola and other infectious diseases: melatonin “goes viral”

2020 ◽  
Vol 3 (1) ◽  
pp. 43-57 ◽  
Author(s):  
Russel J Reiter ◽  
Qiang Ma ◽  
Ramaswamy Sharma
Keyword(s):  
Mortality Rate ◽  
Infectious Diseases ◽  
Hemorrhagic Shock ◽  
Safety Profile ◽  
Ebola Virus ◽  
Viral Infections ◽  
Virus Disease ◽  
Attractive Potential ◽  
Potential Treatment

This review summarizes published reports on the utility of melatonin as a treatment for virus-mediated diseases. Of special note are the data related to the role of melatonin in influencing Ebola virus disease. This infection and deadly condition has no effective treatment and the published works documenting the ability of melatonin to attenuate the severity of viral infections generally and Ebola infection specifically are considered. The capacity of melatonin to prevent one of the major complications of an Ebola infection, i.e., the hemorrhagic shock syndrome, which often contributes to the high mortality rate, is noteworthy. Considering the high safety profile of melatonin, the fact that it is easily produced, inexpensive and can be self-administered makes it an attractive potential treatment for Ebola virus pathology.  

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