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

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.

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

Frontiers in Microbiology ◽

10.3389/fmicb.2021.710067 ◽

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.

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

Xenotransplantation ◽

10.1111/xen.12211 ◽

2015 ◽

Vol 22 (6) ◽

pp. 468-475 ◽

Cited By ~ 2

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

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Three Immunocompetent Small Animal Models That Do Not Support Zika Virus Infection

Pathogens ◽

10.3390/pathogens10080971 ◽

2021 ◽

Vol 10 (8) ◽

pp. 971

Author(s):

Megan R. Miller ◽

Anna C. Fagre ◽

Taylor C. Clarkson ◽

Erin D. Markle ◽

Brian D. Foy

Keyword(s):

Animal Model ◽

New Zealand ◽

Animal Models ◽

Zika Virus ◽

Guinea Pigs ◽

Sexual Transmission ◽

Small Animal ◽

Zikv Infection ◽

Mosquito Bite ◽

Multimammate Mice

Zika virus (ZIKV) is a mosquito-borne flavivirus that is primarily transmitted to humans through the bite of an infected mosquito. ZIKV causes disease in infected humans with added complications of Guillain-Barré syndrome and birth defects in infants born to mothers infected during pregnancy. There are several large immunocompetent animal models for ZIKV including non-human primates (NHPs). NHP models closely reflect human infection; however, due to sample size restrictions, investigations into the effects of transmission route and the impacts on disease dynamics have been understudied. Mice have been widely used for modeling ZIKV infection, yet there are few ZIKV-susceptible immunocompetent mouse models and none of these have been used to investigate sexual transmission. In an effort to identify a small immunocompetent animal model to characterize sexual transmission of ZIKV, we attempt experimental infection of multimammate mice, New Zealand white rabbits, and Hartley guinea pigs. The multimammate mouse is the natural reservoir of Lassa fever virus and has been identified to harbor other human pathogens. Likewise, while NZW rabbits are susceptible to West Nile virus, they have not yet been examined for their susceptibility to infection with ZIKV. Guinea pigs have been successfully used as models for ZIKV infection, but only in immunocompromised life stages (young or pregnant). Here, it was found that the multimammate mouse and New Zealand White (NZW) rabbits are not susceptible ZIKV infection as determined by a lack viral RNA in tissues and fluids collected. Sexually mature male Hartley guinea pigs were inoculated subcutaneously and by mosquito bite, but found to be refractory to ZIKV infection, contrary to findings of other studies in young and pregnant guinea pigs. Interestingly, here it is shown that adult male guinea pigs are not susceptible to ZIKV infection, even when infected by natural route (e.g., mosquito bite). Although a new small animal model for the sexual transmission for ZIKV was not established through this study, these findings provide information on outbred animal species that are not permissive to infection (NZW rabbits and multimammate mice) and new information surrounding limitations of a previously established animal model (guinea pigs).

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

Viruses ◽

10.3390/v13081641 ◽

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.

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Small Animal Model Mimics Poxvirus Infections

Microbe Magazine ◽

10.1128/microbe.2.608.1 ◽

2007 ◽

Vol 2 (12) ◽

pp. 608-608

Keyword(s):

Animal Model ◽

Small Animal ◽

Small Animal Model

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Rat model of smoke inhalation-induced acute lung injury

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2021-000879 ◽

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.

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In vivo functional chronic imaging of a small animal model using optical-resolution photoacoustic microscopy

Medical Physics ◽

10.1118/1.3137572 ◽

2009 ◽

Vol 36 (6Part1) ◽

pp. 2320-2323 ◽

Cited By ~ 42

Author(s):

Song Hu ◽

Konstantin Maslov ◽

Lihong V. Wang

Keyword(s):

Animal Model ◽

Optical Resolution ◽

Small Animal ◽

Photoacoustic Microscopy ◽

Small Animal Model

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

Journal of Spectroscopy ◽

10.1155/2017/3595078 ◽

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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Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection

Journal of Virology ◽

10.1128/jvi.00386-17 ◽

2017 ◽

Vol 91 (14) ◽

Cited By ~ 11

Author(s):

Liang Cui ◽

Jue Hou ◽

Jinling Fang ◽

Yie Hou Lee ◽

Vivian Vasconcelos Costa ◽

...

Keyword(s):

Fatty Acids ◽

Animal Model ◽

Bile Acid ◽

Dengue Virus ◽

Metabolic Pathways ◽

Dengue Infection ◽

Small Animal ◽

Humanized Mice ◽

Small Animal Model ◽

Serum Metabolomics

ABSTRACT Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend—most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. IMPORTANCE Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly increased the challenges in the study of dengue pathogenesis and the development of therapeutics. Metabolomics provides global views of small-molecule metabolites and is a useful tool for finding metabolic pathways related to disease processes. Here, we conducted a serum metabolomics study on a model using humanized mice with dengue infection that had significant levels of human platelets, monocytes/macrophages, and hepatocytes. Forty-eight differential metabolites were identified, and the underlying perturbed metabolic pathways are quite similar to the pathways found to be altered in dengue patients in previous metabolomics studies, indicating that humanized mice could be a highly relevant small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics.

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