scholarly journals The Tree Shrew as a Model for Cancer Research

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Lu ◽  
Hongmei Peng ◽  
Liping Zhong ◽  
Pan Wu ◽  
Jian He ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Tree Shrew ◽  
Clinical Manifestations ◽  
Animal Disease ◽  
Tree Shrews ◽  
Animal Disease Models ◽  
Conserved Genes ◽  
Tumor Research ◽  
Selection Of

Animal disease models are necessary in medical research, and an appropriate animal model is of great importance for studies about the prevention or treatment of cancer. The most important thing in the selection of animal models is to consider the similarity between animals and humans. The tree shrew (Tupaia belangeri) is a squirrel-like mammal which placed in the order Scandentia. Whole-genome sequencing has revealed that tree shrews are extremely similar to primate and humans than to rodents, with many highly conserved genes, which makes the data from studies that use tree shrews as models more convincing and the research outcomes more easily translatable. In tumor research, tree shrews are often used as animal models for hepatic and mammary cancers. As research has progressed, other types of tree shrew tumor models have been developed and exhibit clinical manifestations similar to those of humans. Combining the advantages of both rodents and primates, the tree shrew is expected to be the most powerful animal model for studying tumors.

scholarly journals Zika Virus Infection in Tupaia belangeri Causes Dermatological Manifestations and Confers Protection against Secondary Infection

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Na-Na Zhang ◽  
Li Zhang ◽  
Yong-Qiang Deng ◽  
Yue Feng ◽  
Feng Ma ◽  
...  
Keyword(s):  
Animal Models ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Tree Shrew ◽  
Clinical Manifestations ◽  
Zikv Infection ◽  
Health Crisis ◽  
Tree Shrews ◽  
Tupaia Belangeri

ABSTRACT Animal models of Zika virus (ZIKV) infection have recently been established in mice, guinea pigs, and nonhuman primates. Tree shrews (Tupaia belangeri) are an emerging experimental animal in biomedical applications, but their susceptibility to ZIKV infection has not been explored. In the present study, we show that subcutaneous inoculation of ZIKV led to rapid viremia and viral secretion in saliva, as well as to typical dermatological manifestations characterized by massive diffuse skin rash on the trunk. Global transcriptomic sequencing of peripheral blood mononuclear cells isolated from ZIKV-infected animals revealed systematic gene expression changes related to the inflammatory response and dermatological manifestations. Importantly, ZIKV infection readily triggered the production of high-titer neutralizing antibodies, thus preventing secondary homologous infection in tree shrews. However, neonatal tree shrews succumbed to ZIKV challenge upon intracerebral infection. The tree shrew model described here recapitulates the most common dermatological manifestations observed in ZIKV-infected patients and may greatly facilitate the elucidation of ZIKV pathogenesis and the development of novel vaccines and therapeutics. IMPORTANCE The reemergence of Zika virus (ZIKV) has caused a global public health crisis since 2016, and there are currently no vaccines or antiviral drugs to prevent or treat ZIKV infection. However, considerable advances have been made in understanding the biology and pathogenesis of ZIKV infection. In particular, various animal models have been successfully established to mimic ZIKV infection and its associated neurological diseases and to evaluate potential countermeasures. However, the clinical symptoms in these mouse and nonhuman primate models are different from the common clinical manifestations seen in human ZIKV patients; in particular, dermatological manifestations are rarely recapitulated in these animal models. Here, we developed a new animal model of ZIKV infection in tree shrews, a rat-sized, primate-related mammal. In vitro and in vivo characterization of ZIKV infection in tree shrews established a direct link between ZIKV infection and the immune responses and dermatological manifestations. The tree shrew model described here, as well as other available animal models, provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccines and therapeutics.

scholarly journals Tree shrew cells transduced with human CD4 and CCR5 support early steps of HIV-1 replication, but viral infectivity is restricted by APOBEC3

2021 ◽  
Author(s):  
Meng-Ting Luo ◽  
Dan Mu ◽  
Xiang Yang ◽  
Rong-Hua Luo ◽  
Hong-Yi Zheng ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Tree Shrew ◽  
Human Diseases ◽  
Virus Infectivity ◽  
Viral Infectivity ◽  
Tree Shrews ◽  
Exogenous Expression ◽  
Early Replication ◽  
Hiv 1

The host range of human immunodeficiency virus type 1 (HIV-1) is narrow. Therefore, using ordinary animal models to study HIV-1 replication, pathogenesis, and therapy is impractical. The lack of applicable animal models for HIV-1 research spurred our investigation on whether tree shrews ( Tupaia belangeri chinensis ), which are susceptible to many types of human viruses, can act as an animal model for HIV-1. Here, we report that tree shrew primary cells are refractory to wild-type HIV-1 but support the early replication steps of HIV-1 pseudotyped with the vesicular stomatitis virus glycoprotein envelope (VSV-G), which can bypass entry receptors. The exogenous expression of human CD4 renders the tree shrew cell line infectable to X4-tropic HIV-1 IIIB , suggesting that tree shrew CXCR4 is a functional HIV-1 co-receptor. However, tree shrew cells did not produce infectious HIV-1 progeny virions, even with the human CD4 receptor. Subsequently, we identified tree shrew (ts) apolipoprotein B editing catalytic polypeptide 3 (tsAPOBEC3) proteins as active inhibitors of HIV-1 particle infectivity, with virus infectivity reduced 10–1 000-fold. Unlike human APOBEC3G, the tsA3Z2c-Z1b protein was not degraded by the HIV-1 viral infectivity factor (Vif), but markedly restricted HIV-1 replication through mutagenicity and reverse transcription inhibition. The pooled knockout of tsA3Z2c-Z1b partially restored the infectivity of the HIV-1 progeny. This work suggests that tsAPOBEC3 proteins serve as an additional barrier to the development of HIV-1 tree shrew models, even when virus entry is overcome by exogenous expression of human CD4. IMPORTANCE The development of animal models is critical for studying human diseases and their pathogenesis and for evaluating drug and vaccine efficacy. For improved AIDS research, the ideal animal model of HIV-1 infection should be a small laboratory mammal that closely mimics virus replication in humans. Tree shrews exhibit considerable potential as animal models for the study of human diseases and therapeutic responses. Here, we report that human-CD4-expressing tree shrew cells support the early steps of HIV-1 replication and that tree shrew CXCR4 is a functional co-receptor of HIV-1. However, tree shrew cells harbor additional restrictions that lead to the production of HIV-1 virions with low infectivity. Thus, the tsAPOBEC3 proteins are partial barriers to developing tree shrews as an HIV-1 model. Our results provide insight into the genetic basis of HIV inhibition in tree shrews and build a foundation for the establishment of gene-edited tree shrew HIV-1-infected models.

scholarly journals Tree Shrew Is a Suitable Animal Model for the Study of Epstein Barr Virus

2022 ◽  
Vol 12 ◽  
Author(s):  
Wei Xia ◽  
Honglin Chen ◽  
Yiwei Feng ◽  
Nan Shi ◽  
Zongjian Huang ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Tree Shrew ◽  
Tree Shrews ◽  
Barr Virus ◽  
Ebv Infection ◽  
Suitable Animal Model ◽  
Epstein Barr

Epstein-Barr virus (EBV) is a human herpesvirus that latently infects approximately 95% of adults and is associated with a spectrum of human diseases including Infectious Mononucleosis and a variety of malignancies. However, understanding the pathogenesis, vaccines and antiviral drugs for EBV-associated disease has been hampered by the lack of suitable animal models. Tree shrew is a novel laboratory animal with a close phylogenetic relationship to primates, which is a critical advantage for many animal models for human disease, especially viral infections. Herein, we first identified the key residues in the CR2 receptor that bind the gp350 protein and facilitate viral entry. We found that tree shrew shares 100% sequence identity with humans in these residues, which is much higher than rabbits (50%) and rats (25%). In vitro analysis showed that B lymphocytes of tree shrews are susceptible to EBV infection and replication, as well as EBV-enhanced cell proliferation. Moreover, results of in vivo experiments show that EBV infection in tree shrews resembles EBV infection in humans. The infected animals exhibited transient fever and loss of weight accompanied by neutropenia and high viremia levels during the acute phase of the viral infection. Thereafter, tree shrews acted as asymptomatic carriers of the virus in most cases that EBV-related protein could be detected in blood and tissues. However, a resurgence of EBV infection occurred at 49 dpi. Nanopore transcriptomic sequencing of peripheral blood in EBV-infected animals revealed the dynamic changes in biological processes occurring during EBV primary infection. Importantly, we find that neutrophil function was impaired in tree shrew model as well as human Infectious Mononucleosis datasets (GSE85599 and GSE45918). In addition, retrospective case reviews suggested that neutropenia may play an important role in EBV escaping host innate immune response, leading to long-term latent infection. Our findings demonstrated that tree shrew is a suitable animal model to evaluate the mechanisms of EBV infection, and for developing vaccines and therapeutic drugs against EBV.

scholarly journals Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Porcine Model ◽  
Animal Experiments ◽  
Radioactive Tracers ◽  
The Individual ◽  
Selection Of

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

scholarly journals Phodopus roborovskii SH101 as a systemic infection model of SARS-CoV-2

2021 ◽  
Author(s):  
Chongkai Zhai ◽  
Mingda Wang ◽  
Hea-Jong Chung ◽  
Md. Mehedi Hassan ◽  
Seungkoo Lee ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Respiratory Infection ◽  
Clinical Manifestations ◽  
Systemic Infection ◽  
High Fever ◽  
Hamster Strain ◽  
Respiratory Systems ◽  
Systemic Symptoms ◽  
The Brain

AbstractSevere acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide threat with its unusually high transmission rates and rapid evolution into diverse strains. Unlike typical respiratory viruses, SARS-CoV-2 frequently causes systemic infection by breaking the boundaries of the respiratory systems. The development of animal models recapitulating the clinical manifestations of COVID-19 is of utmost importance not only for the development of vaccines and antivirals but also for understanding the pathogenesis. However, there has not been developed an animal model for systemic infection of SARS-CoV-2 representing most aspects of the clinical manifestations of COVID-19 with systemic symptoms. Here we report that a hamster strain of Phodopus roborovskii SH101, a laboratory inbred hamster strain of P. roborovskii, displayed most symptoms of systemic infection upon SARS-CoV-2 infection as in the case of the human counterpart, unlike current COVID-19 animal models. P. roborovskii SH101 post-infection of SARS-CoV-2 represented most clinical symptoms of COVID-19 such as snuffling, dyspnea, cough, labored breathing, hunched posture, progressive weight loss, and ruffled fur, in addition to high fever following shaking chills. Histological examinations also revealed a serious right-predominated pneumonia as well as slight organ damages in the brain and liver, manifesting systemic COVID-19 cases. Considering the merit of a small animal as well as its clinical manifestations of SARS-CoV-2 infection in human, this hamster model seems to provide an ideal tool to investigate COVID-19.Author summaryAlthough the current animal models supported SARS-CoV-2 replication and displayed varying degrees of illness after SARS-CoV-2 infection, the infections of SARS-CoV-2 were mainly limited to the respiratory systems of these animals, including hACE2 transgenic mice, hamsters, ferrets, fruit bats, guinea pigs, African green monkey, Rhesus macaques, and Cynomolgus macaques. While these animal models can be a modest model for the respiratory infection, there is a clear limit for use them in the study of COVID-19 that also displays multiple systemic symptoms. Therefore, the development of an animal model recapitulating COVID-19-specific symptoms such as the right-predominated pneumonia would be the utmost need to overcome the imminent threat posed by COVID-19. We identified a very interesting hamster strain, Phodopus roborovskii SH101, which mimics almost all aspects of the clinical manifestations of COVID-19 upon SARS-CoV-2 infection. Unlike the current animal models, SARS-CoV-2-infected P. roborovskii SH101 not only displayed the symptoms of respiratory infection but also clinical manifestations specific to human COVID-19 such as high fever following shaking chills, serious right-predominated pneumonia, and minor organ damages in the brain and liver.

scholarly journals Rodent Models to Analyze the Glioma Microenvironment

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110050
Author(s):  
Susann Hetze ◽  
Ulrich Sure ◽  
Manfred Schedlowski ◽  
Martin Hadamitzky ◽  
Lennart Barthel
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Treatment Efficacy ◽  
New Drugs ◽  
Disease Models ◽  
Rodent Models ◽  
Animal Disease ◽  
Basic Principles ◽  
Animal Disease Models ◽  
Glioma Microenvironment

Animal models are still indispensable for understanding the basic principles of glioma development and invasion. Preclinical approaches aim to analyze the treatment efficacy of new drugs before translation into clinical trials is possible. Various animal disease models are available, but not every approach is useful for addressing specific questions. In recent years, it has become increasingly evident that the tumor microenvironment plays a key role in the nature of glioma. In addition to providing an overview, this review evaluates available rodent models in terms of usability for research on the glioma microenvironment.

scholarly journals Mammalian animal models for dengue virus infection: a recent overview

2021 ◽  
Author(s):  
Mohammad Enamul Hoque Kayesh ◽  
Kyoko Tsukiyama-Kohara
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Vaccine Development ◽  
Wide Spectrum ◽  
Tree Shrew ◽  
Clinical Signs ◽  
Denv Infection ◽  
Health Concern

AbstractDengue, a rapidly spreading mosquito-borne human viral disease caused by dengue virus (DENV), is a public health concern in tropical and subtropical areas due to its expanding geographical range. DENV can cause a wide spectrum of illnesses in humans, ranging from asymptomatic infection or mild dengue fever (DF) to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue is caused by four DENV serotypes; however, dengue pathogenesis is complex and poorly understood. Establishing a useful animal model that can exhibit dengue-fever-like signs similar to those in humans is essential to improve our understanding of the host response and pathogenesis of DENV. Although several animal models, including mouse models, non-human primate models, and a recently reported tree shrew model, have been investigated for DENV infection, animal models with clinical signs that are similar to those of DF in humans have not yet been established. Although animal models are essential for understanding the pathogenesis of DENV infection and for drug and vaccine development, each animal model has its own strengths and limitations. Therefore, in this review, we provide a recent overview of animal models for DENV infection and pathogenesis, focusing on studies of the antibody-dependent enhancement (ADE) effect in animal models.

scholarly journals Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Athina Georgiadou ◽  
Claire Dunican ◽  
Pablo Soro-Barrio ◽  
Hyun Jae Lee ◽  
Myrsini Kaforou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Animal Models ◽  
Mouse Models ◽  
Clinical Manifestations ◽  
Plasmodium Yoelii ◽  
Biological Mechanisms ◽  
Microvascular Pathology ◽  
High Parasite ◽  
Comparative Transcriptomic Analysis ◽  
Selection Of

Recent initiatives to improve translation of findings from animal models to human disease have focussed on reproducibility but quantifying the relevance of animal models remains a challenge. Here, we use comparative transcriptomics of blood to evaluate the systemic host response and its concordance between humans with different clinical manifestations of malaria and five commonly used mouse models. Plasmodium yoelii 17XL infection of mice most closely reproduces the profile of gene expression changes seen in the major human severe malaria syndromes, accompanied by high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology. However, there is also considerable discordance of changes in gene expression between the different host species and across all models, indicating that the relevance of biological mechanisms of interest in each model should be assessed before conducting experiments. These data will aid the selection of appropriate models for translational malaria research, and the approach is generalizable to other disease models.

scholarly journals Baboon Model for the Study of Endometriosis

2007 ◽  
Vol 3 (5) ◽  
pp. 637-646 ◽  
Author(s):  
Cleophas M Kyama ◽  
Atilla Mihalyi ◽  
Daniel Chai ◽  
Peter Simsa ◽  
Jason M Mwenda ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Early Detection ◽  
Delayed Diagnosis ◽  
Clinical Manifestations ◽  
Model Systems ◽  
Specific Method ◽  
Molecular Changes ◽  
Baboon Model ◽  
Insight Into

Endometriosis is a benign, estrogen-dependent disease and is now recognized as an enigmatic disease owing to its various clinical manifestations and locations. The lack of a reliable and specific method for the early detection of endometriosis often results in delayed diagnosis. So far, research has born inadequate findings regarding understanding the basic etiology or pathophysiology of endometriosis. Animal models that accurately represent the cellular and molecular changes associated with the initiation and progression of human endometriosis have significant potential to facilitate the development of better methods for the early detection and treatment of endometriosis. A number of animal model systems have been developed for the study of this disease. These models replicate many of the known salient features of human endometriosis. This review provides an insight into the use of the baboon model for studies focused on understanding human endometriosis.

scholarly journals Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

2021 ◽  
Author(s):  
Athina Georgiadou ◽  
Claire Dunican ◽  
Pablo Soro-Barrio ◽  
Hyun Jae Lee ◽  
Myrsini Kaforou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Animal Models ◽  
Mouse Models ◽  
Clinical Manifestations ◽  
Plasmodium Yoelii ◽  
Microvascular Pathology ◽  
High Parasite ◽  
Comparative Transcriptomic Analysis ◽  
Plasmodium Yoelii 17Xl ◽  
Selection Of

Recent initiatives to improve translation of findings from animal models to human disease have focussed on reproducibility but quantifying the relevance of animal models remains a challenge. Here we use comparative transcriptomics of blood to evaluate the systemic host response and its concordance between humans with different clinical manifestations of malaria and five commonly used mouse models. Plasmodium yoelii 17XL infection of mice most closely reproduces the profile of gene expression changes seen in the major human severe malaria syndromes, accompanied by high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology. However, there is also considerable discordance of changes in gene expression between species and across all models, indicating that the relevance of biological mechanisms of interest in each model should be assessed before conducting experiments. Our data will aid selection of appropriate models for translational malaria research, and the approach is generalizable to other disease models.

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