Zoological Research ›› 2014, Vol. 35 ›› Issue (6): 485-491.doi: 10.13918/j.issn.2095-8137.2014.6.485

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Experimental infection of tree shrews(Tupaia belangeri) with Coxsackie virus A16

Jian-Ping LI, Yun LIAO, Ying ZHANG, Jing-Jing WANG, Li-Chun WANG, Kai FENG, Qi-Han LI, Long-Ding LIU   

  1. Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical Colleg, Kunming 650118, China
  • Received:2014-04-11 Revised:2014-05-20 Online:2014-11-08 Published:2014-11-08
  • Contact: Qi-Han LI, Long-Ding LIU E-mail:imbcams.lq@gmail.com;longdingl@gmail.com
  • Supported by:

    This work was supported by the National High-Tech R&D Program (2014ZX09102042), the National Natural Science Foundation of China (81373142) and the Natural Science Foundation of Yunnan Province (2012ZA009)


Coxsackie virus A16 (CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease (HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and severe inflammatory CNS lesions. In this study, experimentally CA16 infected tree shrews(Tupaia belangeri) were used to investigate CA16 pathogenesis. The results showed that both the body temperature and the percentages of blood neutrophilic granulocytes / monocytes of CA16 infected tree shrews increased at 4-7 days post infection. Dynamic distributions of CA16 in different tissues and stools were found at different infection stages. Moreover, the pathological changes in CNS and other organs were also observed. These findings indicate that tree shrews can be used as a viable animal model to study CA16 infection.

Arita M, Nagata N, Sata T, Miyamura T, Shimizu H. 2006. Quantitative analysis of poliomyelitis-like paralysis in mice induced by a poliovirus replicon. The Journal of General Virology, 87(Pt 11): 3317-3327.
Chang LY, Lin TY, Huang YC, Tsao KC, Shih SR, Kuo ML, Ning HC, Chung PW, Kang CM. 1999. Comparison of enterovirus 71 and coxsackievirus A16 clinical illnesses during the Taiwan enterovirus epidemic, 1998. The Pediatric Infectious Disease Journal, 18(12): 1092-1096.
Chen YJ, Meng FY, Mao QY, Li JX, Wang H, Liang ZL, Zhang YT, Gao F, Chen QH, Hu YM, Ge ZJ, Yao X, Guo HJ, Zhu FC, Li XL. 2014. Clinical evaluation for batch consistency of an inactivated enterovirus 71 vaccine in a large-scale phase 3 clinical trial. Human Vaccines & Immunotherapeutics, 10(5): 1366-1372.
Dong CH, Liu LD, Zhao HL, Wang JJ, Liao Y, Zhang XM, Na RX, Liang Y, Wang LC, Li QH. 2011. Immunoprotection elicited by an enterovirus type 71 experimental inactivated vaccine in mice and rhesus monkeys. Vaccine, 29(37): 6269-6275.
Fan Y, Huang ZY, Cao CC, Chen CS, Chen YX, Fan DD, He J, Hou HL, Hu L, Hu XT, Jiang XT, Lai R, Lang YS, Liang B, Liao SG, Mu D, Ma YY, Niu YY, Sun XQ, Xia JQ, Xiao J, Xiong ZQ, Xu L, Yang L, Zhang Y, Zhao W, Zhao XD, Zheng YT, Zhou JM, Zhu YB, Zhang GJ, Wang J, Yao YG. 2013. Genome of the Chinese tree shrew. Nature Communications, 4: 1426.
Goto K, Sanefuji M, Kusuhara K, Nishimura Y, Shimizu H, Kira R, Torisu H, Hara T. 2009. Rhombencephalitis and coxsackievirus A16. Emerging Infectious Diseases, 15(10): 1689-1691.
Han JB, Zhang GH, Duan Y, Ma JP, Zhang XH, Luo RH, Lü LB, Zheng YT. 2011. Sero-epidemiology of six viruses natural infection in Tupaia belangeri chinensis. Zoological Research, 32(1): 11-16. (in Chinese)
Hung HC, Chen TC, Fang MY, Yen KJ, Shih SR, Hsu JT, Tseng CP. 2010. Inhibition of enterovirus 71 replication and the viral 3D polymerase by aurintricarboxylic acid. Journal of Antimicrobial Chemotherapy, 65(4): 676-683.
Li RC, Liu LD, Mo ZJ, Wang XY, Xia JL, Liang ZL, Zhang Y, Li YP, Mao QY, Wang JJ, Jiang L, Dong CH, Che YC, Huang T, Jiang ZW, Xie ZP, Wang LC, Liao Y, Liang Y, Nong Y, Liu JS, Zhao HL, Na RX, Guo L, Pu J, Yang EX, Sun L, Cui PF, Shi HJ, Wang JZ, Li QH. 2014. An inactivated enterovirus 71 vaccine in healthy children. The New England Journal of Medicine, 370(9): 829-837.
Liu QW, Shi JP, Huang XL, Liu F, Cai YC, Lan K, Huang Z. 2014. A murine model of coxsackievirus A16 infection for anti-viral evaluation. Antiviral Research, 105: 26-31.
Lo SH, Huang YC, Huang CG, Tsao KC, Li WC, Hsieh YC, Chiu CH, Lin TY. 2011. Clinical and epidemiologic features of Coxsackievirus A6 infection in children in northern Taiwan between 2004 and 2009. Journal of Microbiology, Immunology and Infection, 44(4): 252-257.
Mao Q, Wang Y, Yao X, Bian L, Wu X, Xu M, Liang Z. 2013. Coxsackievirus A16: Epidemiology, diagnosis, and vaccine. Human Vaccines & Immunotherapeutics, 10(2): 360-367.
Mou J, Dawes M, Li Y, He Y, Ma H, Xie X, Griffiths S, Cheng J. 2014. Severe hand, foot and mouth disease in Shenzhen, South China: what matters most? Epidemiology and Infection, 142(4): 776-788.
Tan CW, Lai JK, Sam IC, Chan YF. 2014. Recent developments in antiviral agents against enterovirus 71 infection. Journal of Biomedical Science, 21: 14.
Ong KC, Badmanathan M, Devi S, Leong KL, Cardosa MJ, Wong KT. 2008. Pathologic characterization of a murine model of human enterovirus 71 encephalomyelitis. Journal of Neuropathology and Experimental Neurology, 67(6): 532-542.
Wang CY, Li LF, Wu MH, Lee CY, Huang LM. 2004a. Fatal coxsackievirus A16 infection. The Pediatric Infectious Disease Journal, 23(3): 275-276.
Wang YF, Chou CT, Lei HY, Liu CC, Wang SM, Yan JJ, Su IJ, Wang JR, Yeh TM, Chen SH, Yu CK. 2004b. A mouse-adapted enterovirus 71 strain causes neurological disease in mice after oral infection. Journal of Virology, 78(15): 7916-7924.
Wang YR, Sun LL, Xiao WL, Chen LY, Wang XF, Pan DM. 2013b. Epidemiology and clinical characteristics of hand foot, and mouth disease in a Shenzhen sentinel hospital from 2009 to 2011. BMC Infectious Diseases, 13: 539.
WHO. 1988. Procedure for Using the Lyophilized LBM Pools for Typing Enterovirus, Geneva.
Xu L, Zhang Y, Liang B, Lü LB, Chen CS, Chen YB, Zhou JM, Yao YG. 2013. Tree shrews under the spot light: emerging model of human diseases. Zoological Research, 34(2): 59-69.
Yang E, Cheng C, Zhang Y, Wang J, Che Y, Pu J, Dong C, Liu L, He Z, Lu S, Zhao Y, Jiang L, Liao Y, Shao C, Li Q. 2014. Comparative study of the immunogenicity in mice and monkeys of an inactivated CA16 vaccine made from a human diploid cell line. Human Vaccines & Immunotherapeutics, 10(5): 1266-1273.
Yang MB, Li N, Li F, Zhu QQ, Liu X, Han QY, Wang YW, Chen YP, Zeng XY, Lv Y, Zhang PP, Yang CL, Liu ZW. 2013. Xanthohumol, a main prenylated chalcone from hops, reduces liver damage and modulates oxidative reaction and apoptosis in hepatitis C virus infected Tupaia belangeri. International Immunopharmacology, 16(4): 466-474.
Zhang XM, Zhao HL, Wang JJ, Liao Y, Na RX, Wang LC, Liu LD, Gao JH, Tang DH, Wang CZ, Li QH. 2011a. Evaluation of immune responses and related patho-inflammatory reactions of a candidate inactivated EV71 vaccine in neonatal monkeys. National Medical Journal of China, 91(28): 1977-1981.
Zhang Y, Cui W, Liu LD, Wang JJ, Zhao HL, Liao Y, Na RX, Dong CH, Wang LC, Xie ZP, Gao JH, Cui PF, Zhang XM, Li QH. 2011b. Pathogenesis study of enterovirus 71 infection in rhesus monkeys. Laboratory Investigation, 91(9): 1337-1350.
Zhang Y, Yang EX, Pu J, Liu LD, Che YC, Wang JJ, Liao Y, Wang LC, Ding D, Zhao T, Ma N, Song M, Wang X, Shen D, Tang DD, Huang HT, Zhang ZX, Chen D, Feng MF, Li QH. 2014. The gene expression profile of peripheral blood mononuclear cells from EV71-infected rhesus infants and the significance in viral pathogenesis. PloS One, 9(1): e83766.
Zhu FC, Xu WB, Xia JL, Liang ZL, Liu Y, Zhang XF, Tan XJ, Wang L, Mao QY, Wu JY, Hu YM, Ji TJ, Song LF, Liang Q, Zhang BM, Gao Q, Li JX, Wang SY, Hu YS, Gu SR, Zhang JH, Yao GH, Gu JX, Wang XS, Zhou YC, Chen CB, Zhang ML, Cao MQ, Wang JZ, Wang H, Wang N. 2014. Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. The New England Journal of Medicine, 370(9): 818-828.

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