scholarly journals Nonhuman Primates Are Protected from Smallpox Virus or Monkeypox Virus Challenges by the Antiviral Drug ST-246

2009 ◽  
Vol 53 (6) ◽  
pp. 2620-2625 ◽  
Author(s):  
John Huggins ◽  
Arthur Goff ◽  
Lisa Hensley ◽  
Eric Mucker ◽  
Josh Shamblin ◽  
...  
Keyword(s):  
Viral Load ◽  
Animal Models ◽  
Nonhuman Primates ◽  
Antiviral Drug ◽  
Small Animal ◽  
Variola Virus ◽  
Monkeypox Virus ◽  
Smallpox Virus ◽  
Oral Dosing ◽  
Small Animal Models

ABSTRACT ST-246, a potent orthopoxvirus egress inhibitor, is safe and effective at preventing disease and death in studies of small-animal models involving challenge by several different pathogenic poxviruses. In this report, the antiviral efficacy of ST-246 in treatment of nonhuman primates infected with variola virus or monkeypox virus was assessed. The data indicate that oral dosing once per day with ST-246 protects animals from poxvirus disease, as measured by reductions in viral load and numbers of lesions and enhancement of survival.

scholarly journals A prairie dog animal model of systemic orthopoxvirus disease using West African and Congo Basin strains of monkeypox virus

2009 ◽  
Vol 90 (2) ◽  
pp. 323-333 ◽  
Author(s):  
Christina L. Hutson ◽  
Victoria A. Olson ◽  
Darin S. Carroll ◽  
Jason A. Abel ◽  
Christine M. Hughes ◽  
...  
Keyword(s):  
Animal Models ◽  
Small Animal ◽  
West African ◽  
Cynomys Ludovicianus ◽  
Congo Basin ◽  
Prairie Dog ◽  
Monkeypox Virus ◽  
Small Animal Models ◽  
Strain Dependent ◽  
Human Primate

Multiple monkeypox virus (MPXV) animal models have been discussed in previous studies, but no small animal models, nor most non-human primate models, demonstrated the protracted asymptomatic incubation phase seen in systemic human orthopoxvirus illness. Herein, we characterize a black-tailed prairie dog (PD) (Cynomys ludovicianus) model of infection, via intranasal and intradermal exposures, with the two MPXV clades. Daily observations of the animals were made (food consumption, general symptoms, disease presentation), while weights and virus evaluations (ocular, nasal, oropharyngeal, faeces, blood) were obtained/made every third day. Generalized rash became apparent 9–12 days post-infection for all animals. Individual animals demonstrated a range of symptoms consistent with human monkeypox disease. Measurable viraemias and excretas were similar for both clade-representative strains and persisted until at least day 21. Greater morbidity was observed in Congo Basin strain-challenged animals and mortality was observed only in the Congo Basin strain-challenged animals. The PD model is valuable for the study of strain-dependent differences in MPXV. Additionally, the model closely mimics human systemic orthopoxvirus disease and may serve as a valuable non-human surrogate for investigations of antivirals and next generation orthopoxvirus vaccines.

scholarly journals Monkeypox Virus Infections in Small Animal Models for Evaluation of Anti-Poxvirus Agents

Viruses ◽  
2010 ◽  
Vol 2 (12) ◽  
pp. 2763-2776 ◽  
Author(s):  
Christina L. Hutson ◽  
Inger K. Damon
Keyword(s):  
Animal Models ◽  
Small Animal ◽  
Virus Infections ◽  
Monkeypox Virus ◽  
Small Animal Models

scholarly journals Identification of Wild-Derived Inbred Mouse Strains Highly Susceptible to Monkeypox Virus Infection for Use as Small Animal Models

2010 ◽  
Vol 84 (16) ◽  
pp. 8172-8180 ◽  
Author(s):  
Jeffrey L. Americo ◽  
Bernard Moss ◽  
Patricia L. Earl
Keyword(s):  
Animal Models ◽  
B Lymphocyte ◽  
Inbred Mouse ◽  
Lethal Dose ◽  
Small Animal ◽  
Congo Basin ◽  
Mouse Strains ◽  
Dependent Manner ◽  
Inbred Mouse Strains ◽  
Monkeypox Virus

ABSTRACT Infection with monkeypox virus (MPXV) causes disease manifestations in humans that are similar, although usually less severe, than those of smallpox. Since routine vaccination for smallpox ceased more than 30 years ago, there is concern that MPXV could be used for bioterrorism. Thus, there is a need to develop animal models to study MPXV infection. Accordingly, we screened 38 inbred mouse strains for susceptibility to MPXV. Three highly susceptible wild-derived inbred strains were identified, of which CAST/EiJ was further developed as a model. Using an intranasal route of infection with an isolate of the Congo Basin clade of MPXV, CAST/EiJ mice exhibited weight loss, morbidity, and death in a dose-dependent manner with a calculated 50% lethal dose (LD50) of 680 PFU, whereas there were no deaths of BALB/c mice at a 10,000-fold higher dose. CAST/EiJ mice exhibited greater MPXV sensitivity when infected via the intraperitoneal route, with an LD50 of 14 PFU. Both routes resulted in MPXV replication in the lung, spleen, and liver. Intranasal infection with an isolate of the less-pathogenic West African clade yielded an LD50 of 7,600 PFU. The immune competence of CAST/EiJ mice was established by immunization with vaccinia virus, which induced antigen-specific T- and B-lymphocyte responses and fully protected mice from lethal doses of MPXV. The new mouse model has the following advantages for studying pathogenesis of MPXV, as well as for evaluation of potential vaccines and therapeutics: relative sensitivity to MPXV through multiple routes, genetic homogeneity, available immunological reagents, and commercial production.

Abstract 228: Alterations of Cardiac Morphology and Function Caused by Cardio-Thoracic Surgery in Small Animal Models of Heart Disease

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Peter Nordbeck ◽  
Leoni Bönhof ◽  
Karl-Heinz Hiller ◽  
Sabine Voll ◽  
Paula Arias ◽  
...  
Keyword(s):  
Body Weight ◽  
Heart Disease ◽  
Animal Models ◽  
Right Ventricular ◽  
Small Animal ◽  
Cardiac Morphology ◽  
Small Animal Models ◽  
And Function

Background: Surgical procedures in small animal models of heart disease, such as artificial ligation of the coronary arteries for experimental myocardial infarction, can evoke alterations in cardiac morphology and function. Such alterations might induce artificial early or long term effects in vivo that might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies in small animal models of heart disease. Methods: Female Wistar rats were matched for weight and distributed to sham left coronary artery ligation or untreated control. Cardiac parameters were then investigated in vivo by high-field MRI over time after the surgical procedure, determining left and right ventricular morphology and function. Additionally, the time course of several metabolic and inflammatory blood parameters was determined. Results: Rats after sham surgery showed a lower body weight for up to 8 weeks after the intervention compared to healthy controls. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in the sham operated rats compared to the controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed prolonged metabolic and inflammatory changes after surgery not related to cardiac disease. Conclusion: There is a small distinct impact of cardio-thoracic surgical procedures on the global integrity of the organism, which in the long term also includes circumscribed repercussions on cardiac morphology and function. This impact has to be considered when analyzing data from respective studies and transferring the findings to conditions in patients.

scholarly journals Small Animal Models of Heart Failure

2009 ◽  
Vol 2 (2) ◽  
pp. 138-144 ◽  
Author(s):  
Richard D. Patten ◽  
Monica R. Hall-Porter
Keyword(s):  
Heart Failure ◽  
Animal Models ◽  
Small Animal ◽  
Small Animal Models

scholarly journals Neuromuscular Development and Disease: Learning From in vitro and in vivo Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Zachary Fralish ◽  
Ethan M. Lotz ◽  
Taylor Chavez ◽  
Alastair Khodabukus ◽  
Nenad Bursac
Keyword(s):  
Skeletal Muscle ◽  
Cell Culture ◽  
Animal Models ◽  
Schwann Cells ◽  
Motor Neurons ◽  
Small Animal ◽  
In Vivo Models ◽  
Small Animal Models

The neuromuscular junction (NMJ) is a specialized cholinergic synaptic interface between a motor neuron and a skeletal muscle fiber that translates presynaptic electrical impulses into motor function. NMJ formation and maintenance require tightly regulated signaling and cellular communication among motor neurons, myogenic cells, and Schwann cells. Neuromuscular diseases (NMDs) can result in loss of NMJ function and motor input leading to paralysis or even death. Although small animal models have been instrumental in advancing our understanding of the NMJ structure and function, the complexities of studying this multi-tissue system in vivo and poor clinical outcomes of candidate therapies developed in small animal models has driven the need for in vitro models of functional human NMJ to complement animal studies. In this review, we discuss prevailing models of NMDs and highlight the current progress and ongoing challenges in developing human iPSC-derived (hiPSC) 3D cell culture models of functional NMJs. We first review in vivo development of motor neurons, skeletal muscle, Schwann cells, and the NMJ alongside current methods for directing the differentiation of relevant cell types from hiPSCs. We further compare the efficacy of modeling NMDs in animals and human cell culture systems in the context of five NMDs: amyotrophic lateral sclerosis, myasthenia gravis, Duchenne muscular dystrophy, myotonic dystrophy, and Pompe disease. Finally, we discuss further work necessary for hiPSC-derived NMJ models to function as effective personalized NMD platforms.

scholarly journals Translational Animal Models for Liver Cancer

2018 ◽  
Vol 2 ◽  
pp. 2 ◽  
Author(s):  
Michele Obeid ◽  
Ramzy C. Khabbaz ◽  
Kelly D. Garcia ◽  
Kyle M. Schachtschneider ◽  
Ron C. Gaba
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Research ◽  
Animal Models ◽  
Liver Cancer ◽  
Small Animal ◽  
Large Animal ◽  
Starting Point ◽  
Perfect Model ◽  
Small Animal Models ◽  
Human Primate

Animal models have become increasingly important in the study of hepatocellular carcinoma (HCC), as they serve as a critical bridge between laboratory-based discoveries and human clinical trials. Developing an ideal animal model for translational use is challenging, as the perfect model must be able to reproduce human disease genetically, anatomically, physiologically, and pathologically. This brief review provides an overview of the animal models currently available for translational liver cancer research, including rodent, rabbit, non-human primate, and pig models, with a focus on their respective benefits and shortcomings. While small animal models offer a solid starting point for investigation, large animal HCC models are becoming increasingly important for translation of preclinical results to clinical practice.

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