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 considera...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.展开更多
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...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.展开更多
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 wer...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.展开更多
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...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.展开更多
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 slig...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.展开更多
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 eig...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.展开更多
Influenza,a highly contagious respiratory infectious disease caused by an influenza virus,is a threat to public health worldwide.Avian influenza viruses(AIVs)have the potential to cause the next pandemic by crossing t...Influenza,a highly contagious respiratory infectious disease caused by an influenza virus,is a threat to public health worldwide.Avian influenza viruses(AIVs)have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome.Here,we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models.In addition,we assessed the pathogenicity of AIVs in ferret models.Moreover,we compared the ability of viruses to replicate in mammalian cells,as well as the receptor-binding preferences of AIV isolates.Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation.Of the 24 AIV isolates tested,A/Mallard/South Korea/KNU2019-34/2019(KNU19-34;H1N1)caused severe bodyweight loss and high mortality in mice.The virus replicated in the lungs,kidneys,and heart.Importantly,KNU19-34-infected ferrets showed high viral loads in both nasal washes and lungs.KNU19-34 replicated rapidly in A549 and bound preferentially to human likeα2,6-linked sialic acids rather than to avian-likeα2,3-linked sialic acids,similar to the pandemic A/California/04/2009(H1N1)strain.Gene segments of KNU19-34 were distributed in Egypt and Asia lineages from 2015 to 2018,and the virus had several amino acid substitutions compared to H1N1 AIV isolates that were non-pathogenic in mice.Collectively,the data suggest that KNU19-34 has zoonotic potential and the possibility of new mutations responsible for mammalian adaptation.展开更多
基金supported by the S&T Program of Hebei(20277705D and 20372601D)Natural Science Foundation of Hebei Province,China (H2020206352)+2 种基金Science and Technology Project of Hebei Education Department (QN2018150)Hebei Medical Science Research Project (20220973)Chinese Medicine Research Program of Hebei Province (2021119)。
文摘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.
基金supported by the National Key Research and Development Program of China[2016YFD0500401,2016YFD0501000,2017YFD0502300,and 2017YFD0500600]
文摘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.
基金Supported by A PhD studentship from Merck Research Laboratories (to Percie du Sert N)
文摘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.
基金supported by the Key Project of National Science Foundation of China (Approval No. 30630049)China National "863" Program (Approval No. 2011AA10A212)the China National "973" Program (Approval No. 2012CB722501)
文摘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.
文摘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.
文摘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.
基金funded by grants from the National Research Foundation of Korea(NRF)grant funded by the Korea government(2018M3A9H4055203 and 2023R1A2C2003679)from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HV23C1857)from KRIBB Research Initiative Program(KGM9942421).
文摘Influenza,a highly contagious respiratory infectious disease caused by an influenza virus,is a threat to public health worldwide.Avian influenza viruses(AIVs)have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome.Here,we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models.In addition,we assessed the pathogenicity of AIVs in ferret models.Moreover,we compared the ability of viruses to replicate in mammalian cells,as well as the receptor-binding preferences of AIV isolates.Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation.Of the 24 AIV isolates tested,A/Mallard/South Korea/KNU2019-34/2019(KNU19-34;H1N1)caused severe bodyweight loss and high mortality in mice.The virus replicated in the lungs,kidneys,and heart.Importantly,KNU19-34-infected ferrets showed high viral loads in both nasal washes and lungs.KNU19-34 replicated rapidly in A549 and bound preferentially to human likeα2,6-linked sialic acids rather than to avian-likeα2,3-linked sialic acids,similar to the pandemic A/California/04/2009(H1N1)strain.Gene segments of KNU19-34 were distributed in Egypt and Asia lineages from 2015 to 2018,and the virus had several amino acid substitutions compared to H1N1 AIV isolates that were non-pathogenic in mice.Collectively,the data suggest that KNU19-34 has zoonotic potential and the possibility of new mutations responsible for mammalian adaptation.
