scholarly journals Tree Shrew as an Emerging Small Animal Model for Human Viral Infection: A Recent Overview

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1641
Author(s):  
Mohammad Enamul Hoque Kayesh ◽  
Takahiro Sanada ◽  
Michinori Kohara ◽  
Kyoko Tsukiyama-Kohara
Keyword(s):  
Animal Model ◽  
Viral Infection ◽  
Vaccine Development ◽  
Natural Infection ◽  
Tree Shrew ◽  
Small Animal ◽  
Influenza Viruses ◽  
Infection Model ◽  
Small Animal Model ◽  
Tupaia Belangeri

Viral infection is a global public health threat causing millions of deaths. A suitable small animal model is essential for viral pathogenesis and host response studies that could be used in antiviral and vaccine development. The tree shrew (Tupaia belangeri or Tupaia belangeri chinenesis), a squirrel-like non-primate small mammal in the Tupaiidae family, has been reported to be susceptible to important human viral pathogens, including hepatitis viruses (e.g., HBV, HCV), respiratory viruses (influenza viruses, SARS-CoV-2, human adenovirus B), arboviruses (Zika virus and dengue virus), and other viruses (e.g., herpes simplex virus, etc.). The pathogenesis of these viruses is not fully understood due to the lack of an economically feasible suitable small animal model mimicking natural infection of human diseases. The tree shrew model significantly contributes towards a better understanding of the infection and pathogenesis of these important human pathogens, highlighting its potential to be used as a viable viral infection model of human viruses. Therefore, in this review, we summarize updates regarding human viral infection in the tree shrew model, which highlights the potential of the tree shrew to be utilized for human viral infection and pathogenesis studies.

scholarly journals Rat-to-Chinese tree shrew heart transplantation is a novel small animal model to study non-Gal-mediated discordant xenograft humoral rejection

2015 ◽  
Vol 22 (6) ◽  
pp. 468-475 ◽  
Author(s):  
WeiLi Chen ◽  
Yuan Wu ◽  
Akira Shimizu ◽  
YinLong Lian ◽  
Masayuki Tasaki ◽  
...  
Keyword(s):  
Animal Model ◽  
Heart Transplantation ◽  
Tree Shrew ◽  
Small Animal ◽  
Humoral Rejection ◽  
Small Animal Model

scholarly journals Syrian hamster as an animal model for the study of human influenza virus infection

2017 ◽  
pp. JVI.01693-17 ◽  
Author(s):  
Kiyoko Iwatsuki-Horimoto ◽  
Noriko Nakajima ◽  
Yurie Ichiko ◽  
Yuko Sakai-Tagawa ◽  
Takeshi Noda ◽  
...  
Keyword(s):  
Animal Model ◽  
Virus Infection ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
Small Animal ◽  
Influenza Viruses ◽  
Human Influenza ◽  
Small Animal Model ◽  
Syrian Hamsters ◽  
B Virus

Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using them as an alternative animal model to mice. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a pdm09 and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were airborne transmissible in these hamsters. Hamsters thus have potential as a small animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as H1N1 virus transmission studies.IMPORTANCEWe found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested are airborne transmitted in these hamsters. Syrian hamsters thus have potential as a small animal model for the study of human influenza viruses.

scholarly journals Establishment of Tree Shrew Animal Model for Kaposi’s Sarcoma-Associated Herpesvirus (HHV-8) Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Daoqun Li ◽  
Zulqarnain Baloch ◽  
Yang Zhao ◽  
Lei Bai ◽  
Xing Wang ◽  
...  
Keyword(s):  
Animal Model ◽  
Kaposi's Sarcoma ◽  
Tree Shrew ◽  
Small Animal ◽  
Kaposi’S Sarcoma ◽  
Primary Cells ◽  
Small Animal Model ◽  
Tree Shrews

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the most common cause of Kaposi’s sarcoma (KS) and other malignant growths in humans. However, the lack of a KSHV-infected small animal model has hampered understanding of the mechanisms of KSHV infection, virus replication, pathogenesis, and persistence. This study was designed to explore the susceptibility of tree shrews as a possible KSHV-infected small animal model. A recombinant GFP (latent)/RFP (lytic)-positive rKSHV.219 strain was used to infect primary cells cultured from different tissues of tree shrews as an in vitro model and adult tree shrews as an in vivo model. KSHV latent nuclear antigen (LANA) and DNA were successfully detected in primary cells of tree shrews. Among them, tree shrew kidney epithelial cells (TSKEC) were the most susceptible cells to KSHV infection compared to other cells. KSHV genomic DNA, mRNA, and KSHV-specific proteins were readily detected in the TSKEC cultured up to 32 dpi. Moreover, KSHV DNA and mRNA transcription were also readily detected in the peripheral blood mononuclear cells (PBMCs) and various tissues of tree shrews infected with KSHV. Haematoxylin and eosin (HE) staining showed lymphocyte infiltration, lymphoid tissue focal aggregation, alveolar wall thickening, hepatocyte edema, hepatic necrosis in the spleen, lung, and liver of KSHV-infected animals. Additionally, immune-histochemical (IHC) staining showed that LANA or ORF62-positive cells were present in the spleen, lung, liver, and kidney of KSHV-infected tree shrews. Here, we have successfully established in vitro and in vivo KSHV latent infection in tree shrews. This small animal model is not only useful for studying the pathogenesis of KSHV in vivo but can also be a useful model to study transmission routes of viral infection and a useful platform to characterize the novel therapeutics against KSHV.

scholarly journals Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus

2021 ◽  
Vol 17 (9) ◽  
pp. e1009633
Author(s):  
Christina L. Hutson ◽  
Ashley V. Kondas ◽  
Jana M. Ritter ◽  
Zachary Reed ◽  
Sharon Dietz Ostergaard ◽  
...  
Keyword(s):  
Animal Model ◽  
Small Animal ◽  
Humanized Mice ◽  
Infection Model ◽  
Variola Virus ◽  
Virus Spread ◽  
Small Animal Model ◽  
Humanized Mouse ◽  
Medical Countermeasures ◽  
Intended Use

Smallpox, caused by the solely human pathogen Variola virus (VARV), was declared eradicated in 1980. While known VARV stocks are secure, smallpox remains a bioterrorist threat agent. Recent U.S. Food and Drug Administration approval of the first smallpox anti-viral (tecovirimat) therapeutic was a successful step forward in smallpox preparedness; however, orthopoxviruses can become resistant to treatment, suggesting a multi-therapeutic approach is necessary. Animal models are required for testing medical countermeasures (MCMs) and ideally MCMs are tested directly against the pathogen of interest. Since VARV only infects humans, a representative animal model for testing therapeutics directly against VARV remains a challenge. Here we show that three different humanized mice strains are highly susceptible to VARV infection, establishing the first small animal model using VARV. In comparison, the non-humanized, immunosuppressed background mouse was not susceptible to systemic VARV infection. Following an intranasal VARV challenge that mimics the natural route for human smallpox transmission, the virus spread systemically within the humanized mouse before mortality (~ 13 days post infection), similar to the time from exposure to symptom onset for ordinary human smallpox. Our identification of a permissive/representative VARV animal model can facilitate testing of MCMs in a manner consistent with their intended use.

scholarly journals Recapitulating Zika Virus Infection in Vagina of Tree Shrew (Tupaia belangeri)

2021 ◽  
Vol 11 ◽  
Author(s):  
Zulqarnain Baloch ◽  
Zhili Shen ◽  
Li Zhang ◽  
Yue Feng ◽  
Daoqun Li ◽  
...  
Keyword(s):  
Animal Model ◽  
Viral Load ◽  
Zika Virus ◽  
Tree Shrew ◽  
Sexual Transmission ◽  
Small Animal ◽  
Female Reproductive Tract ◽  
Small Animal Model ◽  
Tree Shrews ◽  
Female Tree

Sexual transmission of Zika Virus (ZIKV) elevates the risk of its dissemination in the female reproductive tract and causes a serious threat to the fetus. However, the available animal models are not appropriate to investigate sexual transmission, dynamics of ZIKV infection, replication, and shedding. The use of tree shrew as a small animal model of ZIKV vaginal infection was assessed in this study. A total of 23 sexually mature female tree shrews were infected with ZIKV GZ01 via the intravaginal route. There was no significant difference in change of body weight, and the temperature between ZIKV infected and control animals. Viral RNA loads were detected in blood, saliva, urine, and vaginal douching. ZIKV RNA was readily detected in vaginal lavage of 22 animals (95.65%, 22/23) at 1 dpi, and viral load ranged from 104.46 to 107.35 copies/ml, and the peak of viral load appeared at 1 dpi. The expression of key inflammatory genes, such as IL6, 8, CCL5, TNF-a, and CXCL9, was increased in the spleen of ZIKV infected animals. In the current study, female tree shrews have been successfully infected with ZIKV through the vaginal route for the first time. Interestingly, at first, ZIKV replicates at the local site of infection and then spreads throughout the host body to develop a robust systemic infection and mounted a protective immune response. This small animal model is not only valuable for exploring ZIKV sexual transmission and may also help to explain the cause of debilitating manifestations of the fetus in vivo.

scholarly journals Rat model of smoke inhalation-induced acute lung injury

2021 ◽  
Vol 8 (1) ◽  
pp. e000879
Author(s):  
Premila Devi Leiphrakpam ◽  
Hannah R Weber ◽  
Tobi Ogun ◽  
Keely L Buesing
Keyword(s):  
Animal Model ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Caspase 3 ◽  
Small Animal ◽  
Therapeutic Options ◽  
Smoke Inhalation ◽  
Small Animal Model ◽  
Injury Score ◽  
Confounding Variables

BackgroundAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology.ObjectiveTo develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI.MethodsRats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO2), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals.ResultsThe current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO2 and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals.ConclusionWe have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation.

scholarly journals Longitudinal Raman Spectroscopic Observation of Skin Biochemical Changes due to Chemotherapeutic Treatment for Breast Cancer in Small Animal Model

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Myeongsu Seong ◽  
NoSoung Myoung ◽  
Songhyun Lee ◽  
Hyeryun Jeong ◽  
Sang-Youp Yim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Animal Model ◽  
Raman Spectra ◽  
Fiber Optic ◽  
Animal Experiments ◽  
Small Animal ◽  
Fiber Optic Probe ◽  
Small Animal Model ◽  
Biochemical Compositions ◽  
Optic Probe

The cancer field effect (CFE) has been highlighted as one of indirect indications for tissue variations that are insensitive to conventional diagnostic techniques. In this research, we had a hypothesis that chemotherapy for breast cancer would affect skin biochemical compositions that would be reflected by Raman spectral changes. We used a fiber-optic probe-based Raman spectroscopy to perform preliminary animal experiments to validate the hypothesis. Firstly, we verified the probing depth of the fiber-optic probe (~800 μm) using a simple intravenous fat emulsion-filled phantom having a silicon wafer at the bottom inside a cuvette. Then, we obtained Raman spectra during breast cancer treatment by chemotherapy from a small animal model in longitudinal manner. Our results showed that the treatment causes variations of biochemical compositions in the skin. For further validation, the Raman spectra will have to be collected from more populations and spectra will need to be compared with immunohistochemistry of the breast tissue.

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