The SARS-CoV ferret model in an infection–challenge study

Chu, Yong Kyu; Ali, Georgia D.; Jia, Fuli; Li, Qianjun; Kelvin, David J.; Couch, Ronald C.; Harrod, Kevin S.; Hutt, Julie A.; Cameron, Cheryl M.; Weiss, Susan R.; Jonsson, Colleen B.

doi:10.1016/j.virol.2007.12.032

Cited by 108 publications

(103 citation statements)

References 54 publications

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“…The lack of vaccine enhancement of disease is further supported by a recent study in WKVvaccinated and challenged ferrets that were studied for 3 weeks (Darnell et al, 2007). The lack of eosinophilic infiltration is consistent with other reports of ferret infections with SARS-CoV (Chu et al, 2008;Darnell et al, 2007) and differs from the mouse model, in which eosinophil accumulation appears a prominent feature (Czub et al, 2005;Deming et al, 2006). Perhaps this highlights an important intrinsic difference in the species response to virus infection.…”

Section: Discussionsupporting

confidence: 82%

“…The alveolar epithelium was considerably damaged or absent and debris was apparent in the small and intermediate airways with suggestion of bronchial and goblet cell hyperplasia (Fig. 5g-i), consistent with findings recently reported in ferrets 7 days after infection with a lower dose of SARS-CoV (Chu et al, 2008). The changes to the bronchial epithelium seen here at day 2 are also consistent with the prolonged bronchiolar hyperplasia seen in ferrets at 23 days post-infection, again with a lower dose of virus (Darnell et al, 2007).…”

Section: Histopathologysupporting

confidence: 91%

“…The number of animals with each lung pathology are shown. another recent publication (Chu et al, 2008). Ferrets are also outbred, allowing the assessment of a range of individual responses that are documented in human SARS.…”

Section: Discussionmentioning

confidence: 99%

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Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

See

Petric

Lawrence

et al. 2008

Journal of General Virology

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Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage. INTRODUCTIONSevere acute respiratory syndrome (SARS) caused 8098 reported cases and 774 deaths in 26 countries (WHO, 2004a) in a single autumn-to-spring period from 2002 to 2003, and had significant effects on the global economy. Serological evidence suggests zoonotic transmission of SARS coronavirus (CoV) into the human population for several years before this outbreak (Zheng et al., 2004); transmission to humans has continued, resulting in at least four independent non-laboratory associated cases in (Che et al., 2006Fleck, 2004; Guan et al., 2005; WHO, 2004b). The aetiological agent of SARS has been identified as a novel human CoV by sequencing of its genome (Marra et al., 2003;Rota et al., 2003) and by experimental infection of macaques to fulfil Koch's postulates (Fouchier et al., 2003). It is of particular concern as a zoonosis because it can replicate in a large number of animals including cats, pigs, ferrets, foxes, monkeys and rats (Chen et al., 2005; et al., 1996;Olsen, 1993). Although antibodies to CoV N proteins have no virus-neutralizing activity, there is evidence that the protein may provide protection in vivo by induction of cell-mediated immunity, although it has also been suggested to induce eosinophilic infiltrates resulting in immunopathology (Deming et al., 2006;Enjuanes et al., 1995; Stohlman et al., 1995;Wesseling et al., 1993). N protein has been shown to generate CoV-specific CD8 + T cells (Boots et al., 1991;Seo et al., 1997; Stohlman et al., 1993 Stohlman et al., , 1995; it also provides protection in animals in response to infection by animal CoV (Collisson et al., 2000;Seo et al., 1997). In addition, vaccination with SARS N protein decre...

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Section: Discussionsupporting

confidence: 82%

Section: Histopathologysupporting

confidence: 91%

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Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

See

Petric

Lawrence

et al. 2008

Journal of General Virology

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“…However, for many viruses, alternative animal models better recapitulate human physiology and disease. Ferrets ( Mustela putorius furo ) have been employed to study the pathogenesis of a variety of human pathogens, including human and avian influenzas, coronaviruses including severe acute respiratory syndrome (SARS‐CoV), human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), Ebola virus and henipavirus (Nipah virus and Hendra virus) . While ferrets can be productively infected with many of these viruses, a lack of some tools to interrogate ferret immunological responses to infection limits insights that might impact the development of vaccines and/or therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Improving immunological insights into the ferret model of human viral infectious disease

Wong

Layton

Wheatley

et al. 2019

Influenza Resp Viruses

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Influenza Other Respi Viruses. 2019;13:535-546. | 535 wileyonlinelibrary.com/journal/irv 1 | INTRODUC TI ON Animal models have proved critical in developing concepts of immunity to infection. Non-human primates (NHP) are a highly humanrelevant disease model for infectious agents due to high genetic conservation between humans and NHP. 1-3 However, significant cost and ethical issues often necessitate the use of smaller animal models for both basic and translational research. Mice (Mus musculus) are a favoured small animal model due to widespread availability, incisive transgenic models, comprehensive genomic information 4 and readily available reagents. However, for many viruses, alternative animal models better recapitulate human physiology and disease. Ferrets (Mustela putorius furo) have been employed to study the pathogenesis of a variety of human pathogens, including human and avian influenzas, coronaviruses including severe acute respiratory syndrome (SARS-CoV), 5-14 human respiratory syncytial virus (HRSV), 15-20 human metapneumovirus (HMPV), 21 Ebola virus 22-28 and henipavirus (Nipah virus and Hendra virus). 29-34 While ferretscan be productively infected with many of these viruses, a lack of some tools to interrogate ferret immunological responses to infection limits insights that might impact the development of vaccines and/or therapeutics. Here, we review recent insights gained from ferret models of human respiratory diseases, with a major focus on influenza, and highlight several knowledge gaps whose closure will greatly enhance the informational gain from ferret models to advance development of human vaccines and therapeutics. AbstractFerrets are a well-established model for studying both the pathogenesis and transmission of human respiratory viruses and evaluation of antiviral vaccines. Advanced immunological studies would add substantial value to the ferret models of disease but are hindered by the low number of ferret-reactive reagents available for flow cytometry and immunohistochemistry. Nevertheless, progress has been made to understand immune responses in the ferret model with a limited set of ferret-specific reagents and assays. This review examines current immunological insights gained from the ferret model across relevant human respiratory diseases, with a focus on influenza viruses. We highlight key knowledge gaps that need to be bridged to advance the utility of ferrets for immunological studies. K E Y W O R D S ferret, immunology, influenza How to cite this article: Wong J, Layton D, Wheatley AK, Kent SJ. Improving immunological insights into the ferret model of human viral infectious disease. Influenza Other Respi Viruses. 2019;13:535-546. https ://doi.

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“…In the cardiovascular system, investigators have used ferrets to model acute thrombosis and myocardial hypertrophy (Baudet and Ventura-Clapier 1990; Schumacher et al 1996). In the gastrointestinal system, ferrets have a documented susceptibility to infections such as Campylobacter jejuni and Helicobacter pylori (Chu et al 2008; Kirkeby et al 2009; Larin 1955; Lipatov et al 2009; Maher and DeStefano 2004; Matsuoka et al 2009; Reuman et al 1989); and in the pulmonary system, the ferret has been useful as a model for obstructive conditions such as asthma (Kurucz and Szelenyi 2006) and cystic fibrosis (Fisher et al 2011). Researchers have also used ferrets in evaluations of drugs that target human influenza virus (Baras et al 2008; Boltz et al 2008) and SARS coronavirus (Roberts et al 2008; See et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Ferret Thoracic Anatomy by 2-Deoxy-2-(18F)Fluoro-D-Glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Imaging

Wu¹,

Zheng²,

Kraenzle³

et al. 2012

ILAR Journal

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The domestic ferret (Mustela putorius furo) has been a long-standing animal model used in the evaluation and treatment of human diseases. Molecular imaging techniques such as 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET) would be an invaluable method of tracking disease in vivo, but this technique has not been reported in the literature. Thus, the aim of this study was to establish baseline imaging characteristics of PET/computed tomography (CT) with 18F-FDG in the ferret model. Twelve healthy female ferrets were anesthetized and underwent combined PET/CT scanning. After the images were fused, volumes of interest (VOIs) were generated in the liver, heart, thymus, and bilateral lung fields. For each VOI, standardized uptake values (SUVs) were calculated. Additional comparisons were made between radiotracer uptake periods (60, 90, and >90 minutes), intravenous and intraperitoneal injections of 18F-FDG, and respiratory gated and ungated acquisitions. Pulmonary structures and the surrounding thoracic and upper abdominal anatomy were readily identified on the CT scans of all ferrets and were successfully fused with PET. VOIs were created in various tissues with the following SUV calculations: heart (maximum standardized uptake value [SUVMax] 8.60, mean standardized uptake value [SUVMean] 5.42), thymus (SUVMax 3.86, SUVMean 2.59), liver (SUVMax 1.37, SUVMean 0.99), right lung (SUVMax 0.92, SUVMean 0.56), and left lung (SUVMax 0.88, SUVMean 0.51). Sixty- to 90-minute uptake periods were sufficient to separate tissues based on background SUV activity. No gross differences in image quality were seen between intraperitoneal and intravenous injections of 18F-FDG. Respiratory gating also did not have a significant impact on image quality of lung parenchyma. The authors concluded that 18F-FDG PET and CT imaging can be performed successfully in normal healthy ferrets with the parameters identified in this study. They obtained similar imaging features and uptake measurements with and without respiratory gating as well as with intraperitoneal and intravenous 18F-FDG injections. 18F-FDG PET and CT can be a valuable resource for the in vivo tracking of disease progression in future studies that employ the ferret model.

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The SARS-CoV ferret model in an infection–challenge study

Cited by 108 publications

References 54 publications

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

Improving immunological insights into the ferret model of human viral infectious disease

Ferret Thoracic Anatomy by 2-Deoxy-2-(18F)Fluoro-D-Glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Imaging

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