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1.
J Am Assoc Lab Anim Sci ; 62(3): 229-242, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2312336

ABSTRACT

Rodents used in biomedical research are maintained as specific pathogen-free (SPF) by employing biosecurity measures that eliminate and exclude adventitious infectious agents known to confound research. The efficacy of these practices is assessed by routine laboratory testing referred to as health monitoring (HM). This study summarizes the results of HM performed at Charles River Research Animal Diagnostic Services (CR-RADS) on samples submitted by external (non-Charles River) clients between 2003 and 2020. Summarizing this vast amount of data has been made practicable by the recent introduction of end-user business intelligence tools to Excel. HM summaries include the number of samples tested and the percent positive by diagnostic methodology, including direct examination for parasites, cultural isolation and identification for bacteria, serology for antibodies to viruses and fastidious microorganisms, and polymerase chain reaction (PCR) assays for pathogen-specific genomic sequences. Consistent with comparable studies, the percentages of pathogen-positive samples by diagnostic methodology and year interval are referred to as period prevalence estimates (%PE). These %PE substantiate the elimination of once common respiratory pathogens, such as Sendai virus, and reductions in the prevalence of other agents considered common, such as the rodent coronaviruses and parvoviruses. Conversely, the %PE of certain pathogens, for example, murine norovirus (MNV), Helicobacter, Rodentibacter, and parasites remain high, perhaps due to the increasing exchange of genetically engineered mutant (GEM) rodents among researchers and the challenges and high cost of eliminating these agents from rodent housing facilities. Study results also document the growing role of PCR in HM because of its applicability to all pathogen types and its high specificity and sensitivity; moreover, PCR can detect pathogens in samples collected antemortem directly from colony animals and from the environment, thereby improving the detection of host-adapted, environmentally unstable pathogens that are not efficiently transmitted to sentinels by soiled bedding.


Subject(s)
Helicobacter , Pasteurellaceae , Rodent Diseases , Rats , Animals , Mice , Prevalence , Polymerase Chain Reaction , Bacteria , Housing, Animal , Rodent Diseases/diagnosis , Rodent Diseases/epidemiology , Rodent Diseases/microbiology
2.
Zool Res ; 44(3): 505-521, 2023 May 18.
Article in English | MEDLINE | ID: covidwho-2306427

ABSTRACT

Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.


Subject(s)
COVID-19 , Rodent Diseases , Zika Virus Infection , Zika Virus , Humans , Male , Mice , Animals , Testis , NF-kappa B/metabolism , COVID-19/veterinary , SARS-CoV-2/metabolism , Homeostasis , Fertility , Zika Virus/metabolism , Zika Virus Infection/metabolism , Zika Virus Infection/veterinary , Membrane Proteins/metabolism , Phosphoproteins/metabolism , Phosphoproteins/pharmacology , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/pharmacology , Rodent Diseases/metabolism
3.
Zool Res ; 44(2): 323-330, 2023 Mar 18.
Article in English | MEDLINE | ID: covidwho-2288820

ABSTRACT

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 non-human 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.


Subject(s)
COVID-19 , Rodent Diseases , Cricetinae , Animals , Mice , SARS-CoV-2 , COVID-19/veterinary , Ferrets , Peptidyl-Dipeptidase A
4.
Poult Sci ; 102(5): 102620, 2023 May.
Article in English | MEDLINE | ID: covidwho-2287091

ABSTRACT

The gamma-coronavirus infectious bronchitis virus (IBV) has a high mutation rate and mainly invades the respiratory mucosa, making it difficult to prevent and causing great economic losses. Nonstructural protein 16 (NSP16) of IBV QX also not only plays an indispensable role in virus invading but also might hugely influence the antigen's recognition and presentation ability of host BMDCs. Hence, our study tries to illustrate the underline mechanism of how NSP16 influences the immune function of BMDCs. Initially, we found that NSP16 of the QX strain significantly inhibited the antigen presentation ability and immune response of mouse BMDCs, which was stimulated by Poly (I:C) or AIV RNA. Besides mouse BMDCs, we also found that NSP16 of the QX strain also significantly stimulated the chicken BMDCs to activate the interferon signaling pathway. Furthermore, we preliminarily demonstrated that IBV QX NSP16 inhibits the antiviral system by affecting the antigen-presenting function of BMDCs.


Subject(s)
Coronavirus Infections , Infectious bronchitis virus , Poultry Diseases , Rodent Diseases , Animals , Mice , Chickens , Antigen Presentation , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Interferons , Poultry Diseases/prevention & control
5.
BMC Vet Res ; 18(1): 124, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1840993

ABSTRACT

BACKGROUND: Coronaviruses have the potential to cross species barriers. To learn the molecular intersections among the most common coronaviruses of domestic and close-contact animals, we analyzed representative coronavirus genera infecting mouse, rat, rabbit, dog, cat, cattle, white-tailed deer, swine, ferret, mink, alpaca, Rhinolophus bat, dolphin, whale, chicken, duck and turkey hosts; reference or complete genome sequences were available for most of these coronavirus genera. Protein sequence alignments and phylogenetic trees were built for the spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. The host receptors and enzymes aminopeptidase N (APN), angiotensin converting enzyme 2 (ACE2), sialic acid synthase (SAS), transmembrane serine protease 2 (TMPRSS2), dipeptidyl peptidase 4 (DPP4), cathepsin L (and its analogs) and furin were also compared. RESULTS: Overall, the S, E, M, and N proteins segregated according to their viral genera (α, ß, or γ), but the S proteins of alphacoronaviruses lacked conservation of phylogeny. Interestingly, the unique polybasic furin cleavage motif found in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) but not in severe acute respiratory syndrome coronavirus (SARS-CoV) or Middle East respiratory syndrome coronavirus (MERS-CoV) exists in several ß-coronaviruses and a few α- or γ-coronaviruses. Receptors and enzymes retained host species-dependent relationships with one another. Among the hosts, critical ACE2 residues essential for SARS-CoV-2 spike protein binding were most conserved in white-tailed deer and cattle. CONCLUSION: The polybasic furin cleavage motif found in several ß- and other coronaviruses of animals points to the existence of an intermediate host for SARS-CoV-2, and it also offers a counternarrative to the theory of a laboratory-engineered virus. Generally, the S proteins of coronaviruses show crossovers of phylogenies indicative of recombination events. Additionally, the consistency in the segregation of viral proteins of the MERS-like coronavirus (NC_034440.1) from pipistrelle bat supports its classification as a ß-coronavirus. Finally, similarities in host enzymes and receptors did not always explain natural cross-infections. More studies are therefore needed to identify factors that determine the cross-species infectivity of coronaviruses.


Subject(s)
COVID-19 , Cattle Diseases , Deer , Dog Diseases , Middle East Respiratory Syndrome Coronavirus , Rodent Diseases , Swine Diseases , Animals , COVID-19/veterinary , Cattle , Dogs , Ferrets , Mice , Middle East Respiratory Syndrome Coronavirus/genetics , Phylogeny , Rabbits , Rats , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Swine
6.
Open Vet J ; 12(5): 602-611, 2022.
Article in English | MEDLINE | ID: covidwho-2144764

ABSTRACT

Background: The mouse model of human diseases is commonly used for biomedical study, including ß-thalassemia (ß-thal), an inherited hemoglobin disorder. Maintaining the mice strain by natural mating systems is costly and seems impractical, especially during the COVID-19 pandemic. Sperm-freezing is a cost-effective solution for ß-thal mouse colony management. Aim: To determine appropriate cryopreservation media for ß-thal mouse spermatozoa to establish a ß-thal mouse sperm bank. Methods: The epididymal spermatozoa of C57BL/6 wild-type (WT) and ß-globin gene knockout thalassemia (BKO) mice were frozen in four freezing media: I) raffinose-skim milk-monothioglycerol (MTG), II) raffinose-skim milk-glutamine, III) raffinose-egg yolk-glycerol, and IV) egg yolk-TES-Tris. The sperm quality was assessed prior to and following freeze-thawing. Results: Compared with WT counterparts, the viable spermatozoa before freezing exhibiting elevated levels of oxidative stress were significantly greater in BKO (p = 0.01). After thawing, the membrane integrity of BKO spermatozoa preserved in I was significantly lower (p = 0.001). The sperm viability and membrane integrity of BKO males were also inferior when media III and IV were used (p = 0.008-0.027). The amount of oxidative stress in the spermatozoon of BKO mice was significantly greater when preserved in I, III, and IV (p = 0.002-0.044). Comparing freezing media, the motility and acrosome integrity of WT and BKO spermatozoa preserved in IV were significantly higher than those in other media (p < 0.001 to p = 0.01). Spermatozoa with the highest mitochondrial membrane potential were observed in I in both genotypes (p = 0.012 to p > 0.05). The viability, membrane integrity, and oxidative stress of post-thaw BKO spermatozoa did not significantly differ among freezing solutions. Conclusion: Irrespective of freezing media, spermatozoa of BKO males are rather more sensitive to cryopreservation than those of WT. Raffinose-skim milk-MTG/glutamine, raffinose-egg yolk-glycerol, and egg yolk-TES-Tris can all be used to preserve BKO mouse spermatozoa. However, with slightly better sperm characteristics, egg yolk-TES-Tris may be a diluent of choice for BKO mouse sperm cryopreservation. The addition of a reducing agent to thawing media is also strongly recommended to efficiently prevent oxidative stress and therefore improve frozen-thawed sperm survival.


Subject(s)
COVID-19 , Rodent Diseases , beta-Thalassemia , Male , Mice , Animals , Humans , Glycerol/pharmacology , beta-Thalassemia/veterinary , Glutamine/pharmacology , Pandemics , Raffinose/pharmacology , Cryoprotective Agents/pharmacology , Sperm Motility , Mice, Inbred C57BL , COVID-19/veterinary , Spermatozoa , Cryopreservation/veterinary
8.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.10.13.512053

ABSTRACT

We report the transmission of SARS-CoV-2 Omicron variant from a COVID-19 symptomatic individual to two domestic rats, one of which developed severe symptoms. Omicron carries several mutations which permit rodent infection. This report demonstrates that pet, and likely wild, rodents could therefore contribute to SARS-CoV-2 spread and evolution.


Subject(s)
COVID-19 , Rodent Diseases
9.
Transbound Emerg Dis ; 69(4): 1824-1836, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1973738

ABSTRACT

One avian H3N2 influenza virus, providing its PB1 and HA segments, reassorted with one human H2N2 virus and caused a pandemic outbreak in 1968, killing over 1 million people. After its introduction to humanity, the pandemic H3N2 virus continued adapting to humans and has resulted in epidemic outbreaks every influenza season. To understand the functional roles of the originally avian PB1 gene in the circulating strains of human H3N2 influenza viruses, we analyzed the evolution of the PB1 gene in all human H3N2 isolates from 1968 to 2019. We found several specific residues dramatically changed around 2002-2009 and remained stable through to 2019. Then, we verified the functions of these PB1 mutations in the genetic background of the early pandemic virus, A/Hong Kong/1/1968(HK/68), as well as a recent seasonal strain, A/Jiangsu/34/2016 (JS/16). The PB1 V709I or PB1 V113A/K586R/D619N/V709I induced higher polymerase activity of HK/68 in human cells. And the four mutations acted cooperatively that had an increased replication capacity in vitro and in vivo at an early stage of infection. In contrast, the backward mutant, A113V/R586K/N619D/I709V, reduced polymerase activity in human cells. The PB1 I709V decreased viral replication in vitro, but this mutant only showed less effect on mice infection experiment, which suggested influenza A virus evolved in human host was not always consisted with highly replication efficiency and pathogenicity in other mammalian host. Overall, our results demonstrated that the identified PB1 mutations contributed to the viral evolution of human influenza A (H3N2) viruses.


Subject(s)
Influenza A virus , Influenza in Birds , Influenza, Human , Rodent Diseases , Animals , Humans , Influenza A Virus, H3N2 Subtype/genetics , Influenza, Human/epidemiology , Mammals , Mice , Viral Proteins/genetics
10.
Viruses ; 14(7)2022 07 11.
Article in English | MEDLINE | ID: covidwho-1928660

ABSTRACT

Urban environments represent unique ecosystems where dense human populations may come into contact with wildlife species, some of which are established or potential reservoirs for zoonotic pathogens that cause human diseases. Finding practical ways to monitor the presence and/or abundance of zoonotic pathogens is important to estimate the risk of spillover to humans in cities. As brown rats (Rattus norvegicus) are ubiquitous in urban habitats, and are hosts of several zoonotic viruses, we conducted longitudinal sampling of brown rats in Vienna, Austria, a large population center in Central Europe. We investigated rat tissues for the presence of several zoonotic viruses, including flaviviruses, hantaviruses, coronaviruses, poxviruses, hepatitis E virus, encephalomyocarditis virus, and influenza A virus. Although we found no evidence of active infections (all were negative for viral nucleic acids) among 96 rats captured between 2016 and 2018, our study supports the findings of others, suggesting that monitoring urban rats may be an efficient way to estimate the activity of zoonotic viruses in urban environments.


Subject(s)
Rodent Diseases , Viruses , Animals , Cities/epidemiology , Ecosystem , Humans , Rats , Rodent Diseases/epidemiology , Viruses/genetics , Zoonoses/epidemiology
12.
Transbound Emerg Dis ; 69(5): e3297-e3304, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1879106

ABSTRACT

The ongoing coronavirus disease 2019 pandemic and its overlap with the influenza season lead to concerns over severe disease caused by the influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infections. Using a Syrian hamster co-infection model with SARS-CoV-2 and the pandemic influenza virus A/California/04/2009 (H1N1), we found (a) more severe disease in co-infected animals, compared to those infected with influenza virus alone but not SARS-CoV-2 infection alone; (b) altered haematological changes in only co-infected animals and (c) altered influenza virus tropism in the respiratory tracts of co-infected animals. Overall, our study revealed that co-infection with SARS-CoV-2 and influenza virus is associated with altered disease severity and tissue tropism, as well as haematological changes, compared to infection with either virus alone.


Subject(s)
COVID-19 , Coinfection , Influenza A Virus, H1N1 Subtype , Influenza, Human , Rodent Diseases , Animals , COVID-19/veterinary , Coinfection/veterinary , Cricetinae , Humans , Mesocricetus , SARS-CoV-2 , Viral Tropism
13.
Vet Rec ; 190 Suppl 1: 12, 2022 06.
Article in English | MEDLINE | ID: covidwho-1877689

ABSTRACT

The immediate crisis of the UK's Covid-19 pandemic may be over but many in the veterinary professions find themselves still working in crisis mode. Carolyne Crowe will be encouraging vets at BVA Live to take a step back and reassess what they want from their 'new normal'.


Subject(s)
COVID-19 , Rodent Diseases , Veterinarians , Animals , COVID-19/veterinary , Cricetinae , Humans , Occupations , Pandemics
14.
Viruses ; 14(6)2022 06 01.
Article in English | MEDLINE | ID: covidwho-1869831

ABSTRACT

The unprecedented pandemic COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with bats as original reservoirs, has once again highlighted the importance of exploring the interface of wildlife diseases and human health. In this study, we identified a novel Betacoronavirus from bank voles (Myodes glareolus) in Grimsö, Sweden, and this virus is designated as Grimso virus. Repeated detection over three years and an overall prevalence of 3.4% suggest that the virus commonly occurs in bank voles. Furthermore, phylogenetic analyses indicate that the Grimso virus belongs to a highly divergent Embecovirus lineage predominantly associated with bank voles. Given that bank voles are one of the most common rodent species in Sweden and Europe, our findings indicate that Grimso virus might be circulating widely in bank voles and further point out the importance of sentinel surveillance of coronaviruses in wild small mammalian animals, especially in wild rodents.


Subject(s)
COVID-19 , Rodent Diseases , Animals , Arvicolinae , COVID-19/veterinary , Phylogeny , SARS-CoV-2/genetics , Sweden/epidemiology
15.
Zool Res ; 43(3): 457-468, 2022 May 18.
Article in English | MEDLINE | ID: covidwho-1836354

ABSTRACT

COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection, the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits. We recently demonstrated that mast cells (MCs) are an essential mediator of SARS-CoV-2-initiated hyperinflammation. We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury. In this study, we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions in vivo, and demonstrated the benefits of co-administration of antihistamines and antiviral drug remdesivir in SARS-CoV-2-infected mice. Specifically, SARS-CoV-2 spike protein-induced MC degranulation resulted in alveolar-capillary injury, while pretreatment of pulmonary microvascular endothelial cells with antihistamines prevented adhesion junction disruption; predictably, the combination of antiviral drug remdesivir with the antihistamine loratadine, a histamine receptor 1 (HR1) antagonist, dampened viral replication and inflammation, thereby greatly reducing lung injury. Our findings emphasize the crucial role of MCs in SARS-CoV-2-induced inflammation and lung injury and provide a feasible combination antiviral and anti-inflammatory therapy for COVID-19 treatment.


Subject(s)
COVID-19 Drug Treatment , COVID-19 , Lung Injury , Rodent Diseases , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/veterinary , Endothelial Cells , Histamine Antagonists/therapeutic use , Inflammation/drug therapy , Inflammation/etiology , Inflammation/veterinary , Lung Injury/drug therapy , Lung Injury/veterinary , Mice , Rodent Diseases/drug therapy , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
16.
Vet Pathol ; 59(4): 648-660, 2022 07.
Article in English | MEDLINE | ID: covidwho-1832989

ABSTRACT

There is a need to standardize pathologic endpoints in animal models of SARS-CoV-2 infection to help benchmark study quality, improve cross-institutional comparison of data, and assess therapeutic efficacy so that potential drugs and vaccines for SARS-CoV-2 can rapidly advance. The Syrian hamster model is a tractable small animal model for COVID-19 that models clinical disease in humans. Using the hamster model, the authors used traditional pathologic assessment with quantitative image analysis to assess disease outcomes in hamsters administered polyclonal immune sera from previously challenged rhesus macaques. The authors then used quantitative image analysis to assess pathologic endpoints across studies performed at different institutions using different tissue processing protocols. The authors detail pathological features of SARS-CoV-2 infection longitudinally and use immunohistochemistry to quantify myeloid cells and T lymphocyte infiltrates during SARS-CoV-2 infection. High-dose immune sera protected hamsters from weight loss and diminished viral replication in tissues and reduced lung lesions. Cumulative pathology scoring correlated with weight loss and was robust in distinguishing IgG efficacy. In formalin-infused lungs, quantitative measurement of percent area affected also correlated with weight loss but was less robust in non-formalin-infused lungs. Longitudinal immunohistochemical assessment of interstitial macrophage infiltrates showed that peak infiltration corresponded to weight loss, yet quantitative assessment of macrophage, neutrophil, and CD3+ T lymphocyte numbers did not distinguish IgG treatment effects. Here, the authors show that quantitative image analysis was a useful adjunct tool for assessing SARS-CoV-2 treatment outcomes in the hamster model.


Subject(s)
COVID-19 , Rodent Diseases , Animals , COVID-19/veterinary , COVID-19 Vaccines , Cricetinae , Disease Models, Animal , Humans , Immune Sera , Immunoglobulin G , Lung/pathology , Macaca mulatta , Mesocricetus , Rodent Diseases/pathology , SARS-CoV-2 , Weight Loss
17.
Vet Rec ; 190(4): 167, 2022 02.
Article in English | MEDLINE | ID: covidwho-1698148
18.
Vet Pathol ; 59(4): 565-577, 2022 07.
Article in English | MEDLINE | ID: covidwho-1673724

ABSTRACT

The emergence of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inspired rapid research efforts targeting the host range, pathogenesis and transmission mechanisms, and the development of antiviral strategies. Genetically modified mice, rhesus macaques, ferrets, and Syrian golden hamsters have been frequently used in studies of pathogenesis and efficacy of antiviral compounds and vaccines. However, alternatives to in vivo experiments, such as immortalized cell lines, primary respiratory epithelial cells cultured at an air-liquid interface, stem/progenitor cell-derived organoids, or tissue explants, have also been used for isolation of SARS-CoV-2, investigation of cytopathic effects, and pathogen-host interactions. Moreover, initial proof-of-concept studies for testing therapeutic agents can be performed with these tools, showing that animal-sparing cell culture methods could significantly reduce the need for animal models in the future, following the 3R principles of replace, reduce, and refine. So far, only few studies using animal-derived primary cells or tissues have been conducted in SARS-CoV-2 research, although natural infection has been shown to occur in several animal species. Therefore, the need for in-depth investigations on possible interspecies transmission routes and differences in susceptibility to SARS-CoV-2 is urgent. This review gives an overview of studies employing alternative culture systems like primary cell cultures, tissue explants, or organoids for investigations of the pathophysiology and reverse zoonotic potential of SARS-CoV-2 in animals. In addition, future possibilities of SARS-CoV-2 research in animals, including previously neglected methods like the use of precision-cut lung slices, will be outlined.


Subject(s)
COVID-19 , Rodent Diseases , Animals , Antiviral Agents/therapeutic use , COVID-19/veterinary , Cricetinae , Disease Models, Animal , Ferrets , Lung/pathology , Macaca mulatta , Mice , Rodent Diseases/pathology , SARS-CoV-2
19.
Vet Pathol ; 59(4): 602-612, 2022 07.
Article in English | MEDLINE | ID: covidwho-1662392

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes severe viral pneumonia and is associated with a high fatality rate. A substantial proportion of patients infected by SARS-CoV-2 suffer from mild hyposmia to complete loss of olfactory function, resulting in anosmia. However, the pathogenesis of the olfactory dysfunction and comparative pathology of upper respiratory infections with SARS-CoV-2 are unknown. We describe the histopathological, immunohistochemical, and in situ hybridization findings from rodent models of SARS-CoV-2 infection. The main histopathological findings in the olfactory epithelia of K8-hACE2 Tg mice, hACE2 Tg mice, and hamsters were varying degrees of inflammatory lesions, including disordered arrangement, necrosis, exfoliation, and macrophage infiltration of the olfactory epithelia, and inflammatory exudation. On the basis of these observations, the nasal epithelia of these rodent models appeared to develop moderate, mild, and severe rhinitis, respectively. Correspondingly, SARS-CoV-2 viral RNA and antigen were mainly identified in the olfactory epithelia and lamina propria. Moreover, viral RNA was abundant in the cerebrum of K18-hACE2 Tg mice, including the olfactory bulb. The K8-hACE2 Tg mouse, hACE2 Tg mouse, and hamster models could be used to investigate the pathology of SARS-CoV-2 infection in the upper respiratory tract and central nervous system. These models could help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments.


Subject(s)
COVID-19 , Rodent Diseases , Angiotensin-Converting Enzyme 2 , Animals , COVID-19/veterinary , Cricetinae , Disease Models, Animal , Lung/pathology , Melphalan , Mice , Mice, Transgenic , Nasal Mucosa , Peptidyl-Dipeptidase A/genetics , RNA, Viral , Rodent Diseases/pathology , SARS-CoV-2 , gamma-Globulins
20.
Vet Pathol ; 59(4): 661-672, 2022 07.
Article in English | MEDLINE | ID: covidwho-1613175

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an ongoing pandemic with millions of deaths worldwide. Infection of humans can be asymptomatic or result in fever, fatigue, dry cough, dyspnea, and acute respiratory distress syndrome with multiorgan failure in severe cases. The pathogenesis of COVID-19 is not fully understood, and various models employing different species are currently applied. Ferrets can be infected with SARS-CoV-2 and efficiently transmit the virus to contact animals. In contrast to hamsters, ferrets usually show mild disease and viral replication restricted to the upper airways. Most reports have used the intranasal inoculation route, while the intratracheal infection model is not well characterized. Herein, we present clinical, virological, and pathological data from young ferrets intratracheally inoculated with SARS-CoV-2. Infected animals showed no significant clinical signs, and had transient infection with peak viral RNA loads at 4 days postinfection, mild to moderate rhinitis, and pulmonary endothelialitis/vasculitis. Viral antigen was exclusively found in the respiratory epithelium of the nasal cavity, indicating a particular tropism for cells in this location. Viral antigen was associated with epithelial damage and influx of inflammatory cells, including activated neutrophils releasing neutrophil extracellular traps. Scanning electron microscopy of the nasal respiratory mucosa revealed loss of cilia, shedding, and rupture of epithelial cells. The currently established ferret SARS-CoV-2 infection models are comparatively discussed with SARS-CoV-2 pathogenesis in mink, and the advantages and disadvantages of both species as research models for zoonotic betacoronaviruses are highlighted.


Subject(s)
COVID-19 , Rodent Diseases , Animals , Antigens, Viral , COVID-19/veterinary , Cricetinae , Disease Models, Animal , Ferrets , Respiratory Mucosa , SARS-CoV-2
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