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 and Characterization of a Guinea Pig-Adapted Sudan Virus

2015 ◽  
Vol 90 (1) ◽  
pp. 392-399 ◽  
Author(s):  
Gary Wong ◽  
Shihua He ◽  
Haiyan Wei ◽  
Andrea Kroeker ◽  
Jonathan Audet ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Lethal Dose ◽  
Fatal Outcome ◽  
Small Animal ◽  
Disease Outbreak ◽  
Small Animal Model ◽  
Content Type

ABSTRACT Infections with Sudan virus (SUDV), a member of the genus Ebolavirus , result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo , a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 × 10 −2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus , such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.

scholarly journals Emergence of Ebola Virus Disease (EVD): Key Facts

2015 ◽  
Vol 6 (1) ◽  
pp. 35-37
Author(s):  
Md Mahfuzar Rahman ◽  
Farnaz Mehrin ◽  
Fahim Ahmed
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Virus Transmission ◽  
Specific Treatment ◽  
Case Fatality ◽  
Signs And Symptoms ◽  
Hemorrhagic Fever ◽  
Ebola Virus Disease ◽  
Background Information ◽  
Global Threat

The modern emerging infection Ebola Virus Disease (EVD) is of global threat originates from Africa region. This is zoonotic and identified as human diseases or previously called Ebola hemorrhagic fever which is a highly fatal human illness where case fatality rate is found up to 90%. The virus transmission begins from wild animals to human and then spreads within population through human to human. Fruit bats are found as natural host of Ebola virus. There is no specific treatment or vaccine available in the market so far, intensive supportive care is needed for severely ill patients. This paper highlights background information, problem statement, viral characteristics, mode of transmission, signs and symptoms, prevention & vaccination. It also indicates possible actions towards prevention of transmission & personal protection.Anwer Khan Modern Medical College Journal Vol. 6, No. 1: January 2015, Pages 35-37

A model of brain abscess: septic homologous blood clot emboli in rats

1986 ◽  
Vol 64 (1) ◽  
pp. 125-127 ◽  
Author(s):  
Hiroshi Matsuura ◽  
Motoshige Kudo ◽  
Yukio Ikeda ◽  
Kazuo Isayama ◽  
Shozo Nakazawa
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Blood Clot ◽  
Small Animal ◽  
Small Animal Model ◽  
Homologous Blood ◽  
Content Type ◽  
Therapeutic Procedures ◽  
Brain Abscesses ◽  
Fine Print

✓ Brain abscesses in rats were produced by intra-arterial injection of septic homologous blood clot emboli. The production rate was 100% and the histopathological features closely resembled those seen in other animal models and in spontaneously occurring brain abscesses in humans. This small-animal model may be useful for systematic study of the development of brain abscesses as well as for evaluation of various therapeutic procedures.

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 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 The Diversity Outbred Mouse Population Is an Improved Animal Model of Vaccination against Tuberculosis That Reflects Heterogeneity of Protection

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Sherry L. Kurtz ◽  
Amy P. Rossi ◽  
Gillian L. Beamer ◽  
Dan M. Gatti ◽  
Igor Kramnik ◽  
...  
Keyword(s):  
Animal Model ◽  
Full Range ◽  
Small Animal ◽  
Complex Case ◽  
Lung Pathology ◽  
Small Animal Model ◽  
Mouse Population ◽  
Content Type ◽  
Diversity Outbred ◽  
Wide Range

ABSTRACT Many studies of Mycobacterium tuberculosis infection and immunity have used mouse models. However, outcomes of vaccination and challenge with M. tuberculosis in inbred mouse strains do not reflect the full range of outcomes seen in people. Previous studies indicated that the novel Diversity Outbred (DO) mouse population exhibited a spectrum of outcomes after primary aerosol infection with M. tuberculosis. Here, we demonstrate the value of this novel mouse population for studies of vaccination against M. tuberculosis aerosol challenge. Using the only currently licensed tuberculosis vaccine, we found that the DO population readily controlled systemic Mycobacterium bovis BCG bacterial burdens and that BCG vaccination significantly improved survival across the DO population upon challenge with M. tuberculosis. Many individual DO mice that were vaccinated with BCG and then challenged with M. tuberculosis exhibited low bacterial burdens, low or even no systemic dissemination, little weight loss, and only minor lung pathology. In contrast, some BCG-vaccinated DO mice progressed quickly to fulminant disease upon M. tuberculosis challenge. Across the population, most of these disease parameters were at most modestly correlated with each other and were often discordant. This result suggests the need for a multiparameter metric to better characterize “disease” and “protection,” with closer similarity to the complex case definitions used in people. Taken together, these results demonstrate that DO mice provide a novel small-animal model of vaccination against tuberculosis that better reflects the wide spectrum of outcomes seen in people. IMPORTANCE We vaccinated the Diversity Outbred (DO) population of mice with BCG, the only vaccine currently used to protect against tuberculosis, and then challenged them with M. tuberculosis by aerosol. We found that the BCG-vaccinated DO mouse population exhibited a wide range of outcomes, in which outcomes in individual mice ranged from minimal respiratory or systemic disease to fulminant disease and death. The breadth of these outcomes appears similar to the range seen in people, indicating that DO mice may serve as an improved small-animal model to study tuberculosis infection and immunity. Moreover, sophisticated tools are available for the use of these mice to map genes contributing to control of vaccination. Thus, the present studies provided an important new tool in the fight against tuberculosis.

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 Rat model of smoke inhalation-induced acute lung injury

2021 ◽  
Vol 8 (1) ◽  
pp. e000879
Author(s):  
Premila Devi Leiphrakpam ◽  
Hannah R Weber ◽  
Tobi Ogun ◽  
Keely L Buesing
Keyword(s):  
Animal Model ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Caspase 3 ◽  
Small Animal ◽  
Therapeutic Options ◽  
Smoke Inhalation ◽  
Small Animal Model ◽  
Injury Score ◽  
Confounding Variables

BackgroundAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology.ObjectiveTo develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI.MethodsRats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO2), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals.ResultsThe current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO2 and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals.ConclusionWe have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation.

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