Volume 41 Issue 5
Sep.  2020
Turn off MathJax
Article Contents
Ling Xu, Dan-Dan Yu, Yu-Hua Ma, Yu-Lin Yao, Rong-Hua Luo, Xiao-Li Feng, Hou-Rong Cai, Jian-Bao Han, Xue-Hui Wang, Ming-Hua Li, Chang-Wen Ke, Yong-Tang Zheng, Yong-Gang Yao. COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2. Zoological Research, 2020, 41(5): 517-526. doi: 10.24272/j.issn.2095-8137.2020.053
Citation: Ling Xu, Dan-Dan Yu, Yu-Hua Ma, Yu-Lin Yao, Rong-Hua Luo, Xiao-Li Feng, Hou-Rong Cai, Jian-Bao Han, Xue-Hui Wang, Ming-Hua Li, Chang-Wen Ke, Yong-Tang Zheng, Yong-Gang Yao. COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2. Zoological Research, 2020, 41(5): 517-526. doi: 10.24272/j.issn.2095-8137.2020.053

COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2

doi: 10.24272/j.issn.2095-8137.2020.053
Funds:  This work was partly supported by the National Key R&D Program of China (2020YFC0842000 to Y.T.Z.), National Natural Science Foundation of China (U1902215 to Y.G.Y.), National Science and Technology Major Projects of Infectious Disease Funds (2017ZX10304402 to Y.T.Z.), Yunnan Province (2018FB046 to D.D.Y.), and CAS “Light of West China” Program (xbzg-zdsys-201909 to Y.G.Y. and Y.T.Z.)
More Information
  • The coronavirus disease 2019 (COVID-19) pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/ HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here, different aged Chinese tree shrews (adult group, 1 year old; old group, 5–6 years old), which are close relatives to primates, were infected with SARS-CoV-2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days post-inoculation (dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3, 5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Histological analysis of lung tissues from animals at 3 dpi (adult group) and 7 dpi (old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.
  • #Authors contributed equally to this work
  • loading
  • [1]
    Amako Y, Tsukiyama-Kohara K, Katsume A, Hirata Y, Sekiguchi S, Tobita Y, et al. 2010. Pathogenesis of hepatitis C virus infection in Tupaia belangeri. Journal of Virology, 84(1): 303−311. doi:  10.1128/JVI.01448-09
    [2]
    Bao LL, Deng W, Huang BY, Gao H, Liu JN, Ren LL, et al. 2020. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature. doi:  10.1038/s41586-020-2312-y.
    [3]
    Chan JFW, Zhang AJ, Yuan SF, Poon VKM, Chan CCS, Lee ACY, et al. 2020. Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility. Clinical Infectious Diseases. doi:  10.1093/cid/ciaa325.
    [4]
    Duan K, Liu BD, Li CS, Zhang HJ, Yu T, Qu JM, et al. 2020. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proceedings of the National Academy of Sciences of the United States of America, 117(17): 9490−9496. doi:  10.1073/pnas.2004168117
    [5]
    Fan Y, Ye MS, Zhang JY, Xu L, Yu DD, Gu TL, et al. 2019. Chromosomal level assembly and population sequencing of the Chinese tree shrew genome. Zoological Research, 40(6): 506−521. doi:  10.24272/j.issn.2095-8137.2019.063
    [6]
    Gao Q, Bao LL, Mao HY, Wang L, Xu KW, Yang M, et al. 2020. Development of an inactivated vaccine candidate for SARS-CoV-2. Science, 369(6499): 77−81. doi:  10.1126/science.abc1932
    [7]
    Geleris J, Sun YF, Platt J, Zucker J, Baldwin M, Hripcsak G, et al. 2020. Observational study of hydroxychloroquine in hospitalized patients with COVID-19. The New England Journal of Medicine, 382(25): 2411−2418. doi:  10.1056/NEJMoa2012410
    [8]
    Goldman JD, Lye DCB, Hui DS, Marks KM, Bruno R, Montejano R, et al. 2020. Remdesivir for 5 or 10 days in patients with severe COVID-19. The New England Journal of Medicine. doi:  10.1056/NEJMoa2015301.
    [9]
    Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. 2020. Compassionate use of remdesivir for patients with severe COVID-19. The New England Journal of Medicine, 382(24): 2327−2336. doi:  10.1056/NEJMoa2007016
    [10]
    Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. 2020. Clinical characteristics of coronavirus disease 2019 in China. The New England Journal of Medicine, 382(18): 1708−1720. doi:  10.1056/NEJMoa2002032
    [11]
    Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, et al. 2020. Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host Microbe, 27(5): 704−709.e2. doi:  10.1016/j.chom.2020.03.023
    [12]
    Lagier JC, Million M, Gautret P, Colson P, Cortaredona S, Giraud-Gatineau A, et al. 2020. Outcomes of 3, 737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis. Travel Medicine and Infectious Disease. doi:  10.1016/j.tmaid.2020.101791.
    [13]
    Lam TTY, Jia N, Zhang YW, Shum MHH, Jiang JF, Zhu HC, et al. 2020. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Nature. doi:  10.1038/s41586-020-2169-0.
    [14]
    Li LH, Li ZR, Wang EL, Yang R, Xiao Y, Han HB, et al. 2016. Herpes simplex virus 1 infection of tree shrews differs from that of mice in the severity of acute infection and viral transcription in the peripheral nervous system. Journal of Virology, 90(2): 790−804. doi:  10.1128/JVI.02258-15
    [15]
    Li RF, Zanin M, Xia XS, Yang ZF. 2018. The tree shrew as a model for infectious diseases research. Journal of Thoracic Disease, 10(Suppl 19): S2272−S2279.
    [16]
    Lu RJ, Zhao X, Li J, Niu PH, Yang B, Wu HL, et al. 2020a. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet, 395(10224): 565−574. doi:  10.1016/S0140-6736(20)30251-8
    [17]
    Lu SY, Zhao Y, Yu WH, Yang Y, Gao JH, Wang JB, et al. 2020b. Comparison of SARS-CoV-2 infections among 3 species of non-human primates. bioRxiv. doi:  10.1101/2020.04.08.031807.
    [18]
    Million M, Lagier JC, Gautret P, Colson P, Fournier PE, Amrane S, et al. 2020. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France. Travel Medicine and Infectious Disease, 35: 101738. doi:  10.1016/j.tmaid.2020.101738
    [19]
    Munster VJ, Feldmann F, Williamson BN, van Doremalen N, Pérez-Pérez L, Schulz J, et al. 2020. Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. Nature. doi:  10.1038/s41586-020-2324-7.
    [20]
    Reed LJ, Muench H. 1938. A simple method of estimating fifty per cent endpoints. American Journal of Epidemiology, 27(3): 493−497. doi:  10.1093/oxfordjournals.aje.a118408
    [21]
    Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, et al. 2020. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science, 368(6494): 1012−1015. doi:  10.1126/science.abb7314
    [22]
    Shan C, Yao YF, Yang XL, Zhou YW, Gao G, Peng Y, et al. 2020. Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in rhesus macaques. Cell Research. doi:  10.1038/s41422-020-0364-z.
    [23]
    Shi JZ, Wen Z, Zhong GX, Yang HL, Wang C, Huang BY, et al. 2020. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science, 368(6494): 1016−1020. doi:  10.1126/science.abb7015
    [24]
    Tang W, Cao ZJ, Han MF, Wang ZY, Chen JW, Sun WJ, et al. 2020. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ: British Medical Journal, 369: m1849.
    [25]
    Wang DW, Hu B, Hu C, Zhu FF, Liu X, Zhang J, et al. 2020a. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China. JAMA. doi:  10.1001/jama.2020.1585.
    [26]
    Wang ML, Cao RY, Zhang LK, Yang XL, Liu J, Xu MY, et al. 2020b. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research, 30(3): 269−271. doi:  10.1038/s41422-020-0282-0
    [27]
    Wang Q, Schwarzenberger P, Yang F, Zhang JJ, Su JJ, Yang C, et al. 2012. Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis): a model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans. Virology Journal, 9: 170. doi:  10.1186/1743-422X-9-170
    [28]
    Wang YM, Zhang DY, Du GH, Du RH, Zhao JP, Jin Y, et al. 2020c. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet, 395(10236): 1569−1578. doi:  10.1016/S0140-6736(20)31022-9
    [29]
    Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, et al. 2020. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature. doi:  10.1038/s41586-020-2423-5.
    [30]
    Wong G, Bi YH, Wang QH, Chen XW, Zhang ZG, Yao YG. 2020. Zoonotic origins of human coronavirus 2019 (HCoV-19/SARS-CoV-2): why is this work important?. Zoological Research, 41(3): 213−219. doi:  10.24272/j.issn.2095-8137.2020.031
    [31]
    Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. 2020. A new coronavirus associated with human respiratory disease in China. Nature, 579(7798): 265−269. doi:  10.1038/s41586-020-2008-3
    [32]
    Xiao J, Liu R, Chen CS. 2017. Tree shrew (Tupaia belangeri) as a novel laboratory disease animal model. Zoological Research, 38(3): 127−137. doi:  10.24272/j.issn.2095-8137.2017.033
    [33]
    Xiao KP, Zhai JQ, Feng YY, Zhou N, Zhang X, Zou JJ, et al. 2020. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature, 583(7815): 286−289. doi:  10.1038/s41586-020-2313-x
    [34]
    Xu S, Li XY, Yang JY, Wang ZX, Jia Y, Han L, et al. 2019. Comparative pathogenicity and transmissibility of pandemic H1N1, avian H5N1, and human H7N9 influenza viruses in tree shrews. Frontiers in Microbiology, 10: 2955. doi:  10.3389/fmicb.2019.02955
    [35]
    Xu XL, Han MF, Li TT, Sun W, Wang DS, Fu BQ, et al. 2020. Effective treatment of severe COVID-19 patients with tocilizumab. Proceedings of the National Academy of Sciences of the United States of America, 117(20): 10970−10975. doi:  10.1073/pnas.2005615117
    [36]
    Yang XB, Yu Y, Xu JQ, Shu HQ, Xia JA, Liu H, et al. 2020. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine, 8(5): 475−481. doi:  10.1016/S2213-2600(20)30079-5
    [37]
    Yao YG. 2017. Creating animal models, why not use the Chinese tree shrew (Tupaia belangeri chinensis)?. Zoological Research, 38(3): 118−126. doi:  10.24272/j.issn.2095-8137.2017.032
    [38]
    Yu B, Li CZ, Chen P, Zhou N, Wang LY, Li J, et al. 2020a. Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19. Science China Life Sciences. doi:  10.1007/s11427-020-1732-2.
    [39]
    Yu P, Qi FF, Xu YF, Li FD, Liu PP, Liu JY, et al. 2020b. Age-related rhesus macaque models of COVID-19. Animal Models and Experimental Medicine, 3(1): 93−97. doi:  10.1002/ame2.12108
    [40]
    Zhang C, Shi L, Wang FS. 2020a. Liver injury in COVID-19: management and challenges. The Lancet Gastroenterology & Hepatology, 5(5): 428−430.
    [41]
    Zhang MX, Song TZ, Zheng HY, Wang XH, Lu Y, Zhang HD, et al. 2019. Superior intestinal integrity and limited microbial translocation are associated with lower immune activation in SIVmac239-infected northern pig-tailed macaques (Macaca leonina). Zoological Research, 40(6): 522−531. doi:  10.24272/j.issn.2095-8137.2019.047
    [42]
    Zhang T, Wu QF, Zhang ZG. 2020b. Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak. Current Biology, 30(7): 1346−1351.e2. doi:  10.1016/j.cub.2020.03.022
    [43]
    Zhao Y, Wang JB, Kuang DX, Xu JW, Yang ML, Ma CX, et al. 2020. Susceptibility of tree shrew to SARS-CoV-2 infection. bioRxiv. doi:  10.1101/2020.04.30.029736.
    [44]
    Zhou H, Chen X, Hu T, Li J, Song H, Liu YR, et al. 2020a. A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein. Current Biology, 30(11): 2196−2203.e3. doi:  10.1016/j.cub.2020.05.023
    [45]
    Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. 2020b. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798): 270−273. doi:  10.1038/s41586-020-2012-7
    [46]
    Zhu N, Zhang DY, Wang WL, Li XW, Yang B, Song JD, et al. 2020. A novel coronavirus from patients with pneumonia in China, 2019. The New England Journal of Medicine, 382(8): 727−733. doi:  10.1056/NEJMoa2001017
  • Relative Articles

    [1] Tian-Zhang Song, Hong-Yi Zheng, Jian-Bao Han, Lin Jin, Xiang Yang, Feng-Liang Liu, Rong-Hua Luo, Ren-Rong Tian, Hou-Rong Cai, Xiao-Li Feng, Chao Liu, Ming-Hua Li, Yong-Tang Zheng. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zoological Research, 2020, 41(5): 503-516.  doi: 10.24272/j.issn.2095-8137.2020.202
    [2] Alberto Gómez-Carballa, Xabier Bello, Jacobo Pardo-Seco, María Luisa Pérez del Molino, Federico Martinón-Torres, Antonio Salas. Phylogeography of SARS-CoV-2 pandemic in Spain: a story of multiple introductions, micro-geographic stratification, founder effects, and super-spreaders. Zoological Research, 2020, 41(): 1-16.  doi: 10.24272/j.issn.2095-8137.2020.217
    [3] Qi Chen, Zhao-Xia Ma, Li-Bin Xia, Zhen-Ni Ye, Bao-Ling Liu, Tie-Kun Ma, Peng-Fei Bao, Xing-Fei Wu, Cong-Tao Yu, Dai-Ping Ma, Yuan-Yuan Han, Wen-Guang Wang, De-Xuan Kuang, Jie-Jie Dai, Rong-Ping Zhang, Min Hu, Hong Shi, Wen-Lin Wang, Yan-Jiao Li. A tree shrew model for steroid-associated osteonecrosis. Zoological Research, 2020, 41(5): 564-568.  doi: 10.24272/j.issn.2095-8137.2020.061
    [4] Wen-Bin Yu, Guang-Da Tang, Li Zhang, Richard T. Corlett. Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data. Zoological Research, 2020, 41(3): 247-257.  doi: 10.24272/j.issn.2095-8137.2020.022
    [5] Gary Wong, Yu-Hai Bi, Qi-Hui Wang, Xin-Wen Chen, Zhi-Gang Zhang, Yong-Gang Yao. Zoonotic origins of human coronavirus 2019 (HCoV-19 / SARS-CoV-2): why is this work important?. Zoological Research, 2020, 41(3): 213-219.  doi: 10.24272/j.issn.2095-8137.2020.031
    [6] Gary Wong, Wen-Guang Cao, Shi-Hua He, Zi-Rui Zhang, Wen-Jun Zhu, Estella Moffat, Hideki Ebihara, Carissa Embury-Hyatt, Xiang-Guo Qiu. Development and characterization of a guinea pig model for Marburg virus. Zoological Research, 2018, 39(1): 32-41.  doi: 10.24272/j.issn.2095-8137.2017.054
    [7] Yong-Gang Yao. Creating animal models, why not use the Chinese tree shrew (Tupaia belangeri chinensis)?. Zoological Research, 2017, 38(3): 118-126.  doi: 10.24272/j.issn.2095-8137.2017.032
    [8] Ji Xiao, Rong Liu, Ce-Shi Chen. Tree shrew (Tupaia belangeri) as a novel laboratory disease animal model. Zoological Research, 2017, 38(3): 127-137.  doi: 10.24272/j.issn.2095-8137.2017.033
    [9] Ming GUO, Wen-Zhe HO. Animal models to study Mycobacterium tuberculosis and HIV co-infection. Zoological Research, 2014, 35(3): 163-169.  doi: 10.11813/j.issn.0254-5853.2014.3.163
    [10] Xiao-Yan HUANG, Ming-Li LI, Juan XU, Yue-Dong GAO, Wen-Guang WANG, An-Guo YIN, Xiao-Fei LI, Xiao-Mei SUN, Xue-Shan XIA, Jie-Jie DAI. Analysis of the molecular characteristics and cloning of full-length coding sequence of Interleukin-2 in tree shrews. Zoological Research, 2013, 34(2): 121-126.  doi: 10.3724/SP.J.1141.2013.02121
    [11] LI Ming-Li, TIAN Wei-Wei, GAO Yue-Dong, GUO Yan, HUANG Jing-Fei, ZHANG Hua-Tang. Genome-wide prediction of interferon family members of tree shrew and their molecular characteristics analysis. Zoological Research, 2012, 33(1): 67-74.  doi: 10.3724/SP.J.1141.2012.01067
    [12] TIAN Wei-Wei, GAO Yue-Dong, GUO Yan, HUANG Jing-Fei, XIAO Chang, LI Zuo-Sheng, ZHANG Hua-Tang. Cloning of full-length coding sequence of tree shrew CD4 and prediction of its molecular characteristics. Zoological Research, 2012, 33(1): 60-66.  doi: 10.3724/SP.J.1141.2012.01060
    [13] LI Yuan, SU Jian-Jia, YANG Chun, CAO Ji, OU Chao, LIANG Liang, YANG Fang, WANG. Progress on establishment of tree shrew(Tupaia) chronic infection with HBV in vivo. Zoological Research, 2011, 32(1): 104-108.  doi: 10.3724/SP.J.1141.2011.01104
    [14] SHEN Pei-Qing, ZHENG Hong, LIU Ru-Wen, CHEN Li-Ling, LI Bo, HE Bao-Li, LI Jin-Tao, BE. Progress and prospect in research on laboratory tree shrew in China. Zoological Research, 2011, 32(1): 109-114.  doi: 10.3724/SP.J.1141.2011.01109
    [15] LI Yao, DAI Jie-Jie, SUN Xiao-Mei, XIA Xue-Shan. Progress in studies on HCV receptor of Tupaia as a potential hepatitis C animal model. Zoological Research, 2011, 32(1): 97-103.  doi: 10.3724/SP.J.1141.2011.01097
    [16] LI Yi-Jiang, GAO Yue-Dong, GUO Yan, LU Cai-Xia, HUANG Jing-Fei, XIA Xue-Shan, DA. Cloning of full-length coding sequence of tree shrew CD3ε and prediction of its molecular characteristics. Zoological Research, 2010, 31(5): 483-489.  doi: 10.3724/SP.J.1141.2010.05483
    [17] ZHANG Gao-hong, CHEN Ya-li, TANG Hong, ZHENG Yong-tang. Humanized SCID Mouse:A Small Animal Model for HIV Research. Zoological Research, 2004, 25(4): 356-362.
    [18] ZHOU Tian-lu, ZHONG Yong-mei, LI Xia, SU Zhao-yu. Circadlan Rhythm of Urination and Its Change After Suprachiasmatic Nucleus Lesion in Tree Shrews. Zoological Research, 1998, 19(5): 374-378.
    [19] JI Wei-zhi, ZOU Ru-jin, YANG Shang-chuan. A Comparative Study of Lactate Dehydrogenase (LDH) Isozymes in Yunnan and Guangxi Tree Shrews. Zoological Research, 1989, 10(zk): 69-77.
    [20] TIAN Bao-ping, PEN Yian-zhang, HOU Yi-di. Investigation of Parasites on Chinese Tree Shrews. Zoological Research, 1989, 10(zk): 90-110.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(5)  / Tables(2)

    Article Metrics

    Article views (1082) PDF downloads(246) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return