scholarly journals A robust human norovirus replication model in zebrafish larvae

2019 ◽  
Author(s):  
Jana Van Dycke ◽  
Annelii Ny ◽  
Nádia Conceição-Neto ◽  
Jan Maes ◽  
Myra Hosmillo ◽  
...  
Keyword(s):  
Danio Rerio ◽  
Antiviral Treatment ◽  
Small Animal ◽  
Societal Cost ◽  
Human Norovirus ◽  
Zebrafish Larvae ◽  
Hematopoietic Lineage ◽  
Liver And Pancreas ◽  
Small Animal Models ◽  
Replication Model

Human noroviruses (HuNoVs) are an important cause of epidemic and endemic acute gastroenteritis worldwide; annually about 700 million people develop a HuNoV infection resulting in ∼219,000 deaths and a societal cost estimated at 60 billion US dollars 1. The lack of robust small animal models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics against HuNoV. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; replication peaks at day 2 post infection and is detectable for at least 6 days. HuNoV is detected in cells of the hematopoietic lineage, the intestine, liver and pancreas. Antiviral treatment reduces HuNoV replication by >2 log10, showing that this model is suited for antiviral studies. Downregulation of fucosyltransferase 8 (fut8) in the larvae reduces HuNoV replication, highlighting a common feature with infection in humans. Zebrafish larvae constitute a simple and robust replication model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.

scholarly journals A robust human norovirus replication model in zebrafish larvae

2019 ◽  
Vol 15 (9) ◽  
pp. e1008009 ◽  
Author(s):  
Jana Van Dycke ◽  
Annelii Ny ◽  
Nádia Conceição-Neto ◽  
Jan Maes ◽  
Myra Hosmillo ◽  
...  
Keyword(s):  
Human Norovirus ◽  
Zebrafish Larvae ◽  
Replication Model

scholarly journals A Mouse Model of Lethal Infection for Evaluating Prophylactics and Therapeutics against Monkeypox Virus

2010 ◽  
Vol 84 (8) ◽  
pp. 3909-3920 ◽  
Author(s):  
Jennifer Stabenow ◽  
R. Mark Buller ◽  
Jill Schriewer ◽  
Cheri West ◽  
John E. Sagartz ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Low Dose ◽  
Antiviral Treatment ◽  
Small Animal ◽  
Booster Vaccination ◽  
Monkeypox Virus ◽  
Modified Vaccinia Virus Ankara ◽  
Lethal Infection ◽  
Single Vaccination ◽  
Small Animal Models

ABSTRACT Monkeypox virus (MPXV) is an orthopoxvirus closely related to variola, the etiological agent of smallpox. In humans, MPXV causes a disease similar to smallpox and is considered to be an emerging infectious disease. Moreover, the use of MPXV for bioterroristic/biowarfare activities is of significant concern. Available small animal models of human monkeypox have been restricted to mammals with poorly defined biologies that also have limited reagent availability. We have established a murine MPXV model utilizing the STAT1-deficient C57BL/6 mouse. Here we report that a relatively low-dose intranasal (IN) infection induces 100% mortality in the stat1 − / − model by day 10 postinfection with high infectious titers in the livers, spleens, and lungs of moribund animals. Vaccination with modified vaccinia virus Ankara (MVA) followed by a booster vaccination is sufficient to protect against an intranasal MPXV challenge and induces an immune response more robust than that of a single vaccination. Furthermore, antiviral treatment with CMX001 (HDP-cidofovir) and ST-246 protects when administered as a regimen initiated on the day of infection. Thus, the stat1 − / − model provides a lethal murine platform for evaluating therapeutics and for investigating the immunological and pathological responses to MPXV infection.

scholarly journals Rationally repurposed nitroxoline inhibits preclinical models of Epstein–Barr virus-associated lymphoproliferation

2021 ◽  
Author(s):  
Maite Ibáñez de Garayo ◽  
Wendi Liu ◽  
Nicole C. Rondeau ◽  
Christopher B. Damoci ◽  
JJ L. Miranda
Keyword(s):  
Epstein Barr Virus ◽  
Small Animal ◽  
Preclinical Models ◽  
Bet Inhibitor ◽  
Barr Virus ◽  
Chelating Activity ◽  
Metal Chelating ◽  
Small Animal Models ◽  
Epstein Barr ◽  
Tract Infections

AbstractRepurposing of currently used drugs for new indications benefits from known experience with those agents. Rational repurposing can be achieved when newly uncovered molecular activities are leveraged against diseases that utilize those mechanisms. Nitroxoline is an antibiotic with metal-chelating activity used to treat urinary tract infections. This small molecule also inhibits the function of bromodomain and extraterminal (BET) proteins that regulate oncogene expression in cancer. Lymphoproliferation driven by the Epstein–Barr virus (EBV) depends on these same proteins. We therefore tested the efficacy of nitroxoline against cell culture and small animal models of EBV-associated lymphoproliferation. Nitroxoline indeed reduces cell and tumor growth. Nitroxoline also acts faster than the prototype BET inhibitor JQ1. We suggest that this rational repurposing may hold translational promise.

scholarly journals History of IgA Nephropathy Mouse Models

2021 ◽  
Vol 10 (14) ◽  
pp. 3142
Author(s):  
Batoul Wehbi ◽  
Virginie Pascal ◽  
Lina Zawil ◽  
Michel Cogné ◽  
Jean-Claude Aldigier
Keyword(s):  
Iga Nephropathy ◽  
Small Animal ◽  
Experimental Models ◽  
Murine Models ◽  
Therapeutic Approaches ◽  
Complement Components ◽  
Simple Description ◽  
Primary Glomerulonephritis ◽  
History Of ◽  
Small Animal Models

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. It was first described in 1968 by Jean Berger and Nicole Hinglais as the presence of intercapillary deposits of IgA. Despite this simple description, patients with IgAN may present very broad clinical features ranging from the isolated presence of IgA in the mesangium without clinical or biological manifestations to rapidly progressive kidney failure. These features are associated with a variety of histological lesions, from the discrete thickening of the mesangial matrix to diffuse cell proliferation. Immunofluorescence on IgAN kidney specimens shows the isolated presence of IgA or its inconsistent association with IgG and complement components. This clinical heterogeneity of IgAN clearly echoes its complex and multifactorial pathophysiology in humans, inviting further analyses of its various aspects through the use of experimental models. Small-animal models of IgAN provide the most pertinent strategies for studying the multifactorial aspects of IgAN pathogenesis and progression. Although only primates have the IgA1 subclass, several murine models have been developed in which various aspects of immune responses are deregulated and which are useful in the understanding of IgAN physiopathology as well as in the assessment of IgAN therapeutic approaches. In this manuscript, we review all murine IgAN models developed since 1968 and discuss their remarkable contribution to understanding the disease.

scholarly journals Fucoidan But Not 2′-Fucosyllactose Inhibits Human Norovirus Replication in Zebrafish Larvae

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 461
Author(s):  
Malcolm Turk Hsern Tan ◽  
Yan Li ◽  
Mohamad Eshaghi Gorji ◽  
Zhiyuan Gong ◽  
Dan Li
Keyword(s):  
Brown Algae ◽  
Disease Burden ◽  
Type A ◽  
Fucus Vesiculosus ◽  
Human Norovirus ◽  
Human Noroviruses ◽  
Molecular Weights ◽  
Zebrafish Larvae ◽  
Virus Like Particle

Human noroviruses (hNoVs) cause heavy disease burden worldwide and there is no clinically approved vaccination or antiviral hitherto. In this study, with the use of a zebrafish larva in vivo platform, we investigated the anti-hNoV potentials of fucoidan (from brown algae Fucus vesiculosus) and 2′-Fucosyllactose (2′-FL). As a result, although both fucoidan and 2′-FL were able to block hNoV GII.4 virus-like particle (VLPs) from binding to type A saliva as expected, only fucoidan, but not 2′-FL, was able to inhibit the replication of hNoV GII.P16-GII.4 in zebrafish larvae, indicating the possible needs of higher molecular weights for fucosylated carbohydrates to exert anti-hNoV effect.

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.

Neurobehavioral effects of bisphenol S exposure in early life stages of zebrafish larvae (Danio rerio)

Chemosphere ◽  
2019 ◽  
Vol 217 ◽  
pp. 629-635 ◽  
Author(s):  
Jie Gu ◽  
Jiayao Zhang ◽  
Yaoyao Chen ◽  
Hongye Wang ◽  
Min Guo ◽  
...  
Keyword(s):  
Danio Rerio ◽  
Early Life ◽  
Life Stages ◽  
Early Life Stages ◽  
Bisphenol S ◽  
Zebrafish Larvae ◽  
Neurobehavioral Effects
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