Ferrets: A powerful model of SARS-CoV-2

The rapid spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social,economic,and health burdens worldwide.Despite considerable efforts to combat coronavirus disease 2019(COVID-19),various SARS-CoV-2 variants have emerged,and their underlying mechanisms of pathogenicity remain largely unknown.Furthermore,effective therapeutic drugs are still under development.Thus,an ideal animal model is crucial for studying the pathogenesis of COVID-19 and for the preclinical evaluation of vaccines and antivirals against SARS-CoV-2 and variant infections.Currently,several animal models,including mice,hamsters,ferrets,and nonhuman primates(NHPs),have been established to study COVID-19.Among them,ferrets are naturally susceptible to SARS-CoV-2 infection and are considered suitable for COVID-19 study.Here,we summarize recent developments and application of SARS-CoV-2 ferret models in studies on pathogenesis,therapeutic agents,and vaccines,and provide a perspective on the role of these models in preventing COVID-19 spread.

Immunogenic and Protective Properties of the First Kazakhstan Vaccine against Pandemic Influenza А(Н1N1) pdm09 in Ferrets

This paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine （Refluvac） on ferret models. For this purpose, groups of eight ferrets （6 to 7 months old） were injected with 0.5 mL of vaccine specimens containing 3.75, 7.5 or 15.0 μg of virus hemagglutinin. Administration was intramuscular and given either as a single dose or as two doses 14 days apart. All vaccine specimens manifested immunogenicity in ferrets for single （HI titer, from 51 ± 7 to 160 ± 23） and double （HI titer, from 697± 120 to 829 ± 117） administrations. To assess the protective effects of the vaccine, ferrets from the vaccinated and control groups were infected intranasally with pandemic virus A/California/7/09 （H1N1） pdm09 at a dose of 106 106/0.5 mL. Fourteen days post-infection, the ferrets inoculated with single or double vaccines containing 3.75, 7.5 or 15.0 ~g of hemagglutinin per dose showed no signs of influenza infection, weight loss, or body temperature rise, and no premature deaths occurred. The number of vaccinated ferrets shedding the virus via the upper airway, as well as the amount of virus shed after infection, was significantly reduced in comparison with animals from the control group. Based on our results, we suggest that a single vaccination at a dose of 3.75 or 7.5 μg hemagglutinin be used for Phase I clinical trials.

Reduced normogastric electrical activity associated with emesis:A telemetric study in ferrets

AIM： To characterize the gastric myoelectric activity （GMA） and intra-abdominal pressure changes induced by emetic stimuli （apomorphine and cisplatin） in the ferret. METHODS： GMA and intra-abdominal pressure were recorded in conscious, unrestrained ferrets surgically implanted with radiotelemetry transmitters. Animals were challenged with apomorphine （0.25 mg/kg sc） and cisplatin （10 mg/kg ip）, and the emetic response was quantified via direct observation and intra-abdominal pressure recording for 1 and 4 h, respectively. The GMA was analyzed by spectral analysis; the parameters used to characterize the GMA were the dominant frequency （DF） and the repartition of spectral power in the bradygastric, normogastric and tachygastric frequency ranges. RESULTS： Retches were identified on the intraabdominal pressure trace as peaks 0.30 ± 1.01 s in duration and 59.57 ± 2.74 mmHg in amplitude, vomit peaks were longer （0.82 ± 0.06 s, P 〈 0.01） and reached a higher pressure （87.73 ± 8.12 mmHg, P 〈 0.001）. The number of retches and vomits quantified via direct observation [apomorphine： 65.5 ± 11.8 retches ± vomits （R＋V）, cisplatin： 202.6 ± 64.1 R＋V] and intra-abdominal pressure （apomorphine： 68.3± 13.7 R＋V, n = 8; cisplatin： 219.0 ± 69.2 R＋V, n = 8） were correlated （r = 0.97, P 〈 0.0001） and the timing of emesis was consistent between the 2 methods. Apomorphine induced a decrease in normogastria from 45.48% ± 4.35% to 36.70 ± 4.34% （n = 8, P 〈 0.05） but the DF of the slow waves was not changed [8.95 ± 0.25 counts/rain （cpm） vs 8.68 ± 0.35 cpm, n = 8, P 〉 0.05]. Cisplatin induced a decrease in normogastria from 55.83% ± 4.30% to 29.22% ± 5.16% and an increase in bradygastria from 14.28% ± 2.32% to 31.19% ± 8.33% （n = 8, P 〈 0.001） but the DF （9.14 ± 0.13 cpm） remained unchanged （P 〉 0.05）. The GMA changes induced by cisplatin preceded the emetic response as normogastria was reduced for 1 h before the onset of emesis （57.61% ± 5.66% to 39.91% ± 5.74%, n = 6, P 〈 0.05）. Peri-emesis analysis revealed that the GMA was significantly disturbed during and immediately after, but not immediately before, the emetic episodes. CONCLUSION： The induction of emesis is reliably associated with a disrupted GMA, but changes may also occur prior to and following the emetic response.

不规则裂纹宽度的一种分段评定法

针对表面裂纹边缘轮廓的不规则特性,提出了一种分段宽度评定方法.利用计算机数字图像处理的方法,在获得表面图像后,对该图像沿纵向进行分段,分别对每段的裂纹宽度用Ferret算法进行评定.为了比较不同的分段方法的优劣,提出有用信息利用率的概念,从几种分段方法中选出一种最优的方法进行分段评定,最后得出该裂纹宽度的定量评定.经过实例验证,用此方法可以定量评定裂纹的宽度,评定的结果可以为机械结构表面检测提供有效依据,该方法也可应用于一般不规则图形几何尺寸的定量评定.

基于数字图像处理技术的岩石节理宽度测量

介绍了采用数字图像处理技术对不规则岩石节理裂隙进行宽度测量的不同方法。对比 分析了常用的等面积圆算法、等面积椭圆算法和简单Ferret算法的应用缺陷,提出了改进的Ferret 算法,详细说明了其实现原理,并通过实例验证了改进的Ferret算法的可行性。

Emerging New Phylogenetic Groups of Rabies Virus in Chinese Ferret Badgers

Chinese ferret badger（FB）-transmitted rabies is a serious threat to public health in southeast China. Although mostly associated with dogs, the rabies virus（RABV） presents genetic diversity and has a significantly wide host range in China. Instead of the dog-and wildlife-associated China ⅠI lineage in the past decades, the China Ⅰ lineage has become the main epidemic group hosted and transmitted by dogs. In this study, four new lineages, including 43 RABVs from FBs, have been classified within the dog-dominated China Ⅰ lineage since 2014. FBRABVs have been previously categorized in the China Ⅱ lineage. Moreover, FB-hosted viruses seem to have become the main independent FB-associated clade in the phylogenetic tree. This claim suggests that the increasing genetic diversity of RABVs in FBs is a result of the selective pressure from coexisting dog rabies. FB transmission has become complicated and serious with the coexistence of dog rabies. Therefore, apart from targeting FB rabies, priority should be provided by the appropriate state agencies to perform mass immunization of dog against rabies.

Epidemic and Maintenance of Rabies in Chinese Ferret Badgers (Melogale moschata) indicated by Epidemiology and the Molecular Signatures of Rabies Viruses

An epidemic of Chinese ferret badger-associated human rabies was investigated in Wuyuan county, Jiangxi province and rabies viruses isolates from ferret badgers in different districts in Jiangxi and Zhejiang provinces were sequenced with their nucleotides and amino acids and aligned for epidemiological analysis. The results showed that the human rabies in Wuyuan are only associated with ferret badger bites; the rabies virus can be isolated in a high percentage of ferret badgers in the epidemic areas in Jiangxi and Zhejiang provinces; the isolates share the same molecular features in nucleotides and have characteristic amino acid signatures, i.e., 2 sites in the nucleoprotein and 3 sites in the glycoprotein, that are distinct from virus isolates from dogs in the same region. We conclude that rabies in Chinese ferret badgers has formed an independent transmission cycle and ferret badgers may serve as another important rabies reservoir independent of dog rabies in China.

Chronic atrophic endometritis and pyometra in a ferret: A case report

The aim of this report was to describe a clinical case of chronic atrophic endometritis as a complication of cystic endometrial hyperplasia-pyometra complex in a non-spayed ferret. The ferret was presented with a slight abdominal distension and odorless purulent vulvar discharge after unsuccessful medical treatment with enrofloxacine and aglepristone 2 months ago in another clinic. Ultrasonography revealed enlarged uterine horns filled with fluid and blood laboratory analysis showed anaemia and leukocytosis, so diagnosis of pyometra was made. Laparotomy and ovariohysterectomy were performed. Histopathological and microbiological examination of the uterus revealed the presence of purulent atrophic endometritis caused by Staphylococcus spp. In conclusion, this is a very rare case of endometrial atrophia after chronic uterine inflammation in a ferret.

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