The Experimental Infection Of Tupaia Belangeri Chinenses With Coxsackievirus Virus A16

Hand, foot and mouth disease (HFMD) was a worldwide infectious disease in children, caused by Enteroviruses. Coxsackievirus A16(CA16) was one of the two major pathogens of HFMD, which had not received much attention, due to its asymptomatic or mild clinical symptoms after infection. However, there had been more and more reports on the infection of CA16, showing that it may also lead to the complication of myocarditis, refractory shock and other lethalcomplications, especially the proportion of HFMD cases caused by CA16in some areas had been reported. The infection of CA16was a serious threat to life and health in infants, and more attentions should be given to study CA16in depth. The pathogenic mechanism of CA16remains at the stage of exploring, therefore, it is very important to establish an appropriate animal model for further study, vaccine development and pharmaceutical research.At present the main successful animal model reported about CA16infection was suckling mouse, but its short infection time limits the application of basic research and vaccine evaluation. Moreover, such rodent model can not fully reflect the infection progress and pathological effects caused by CA16.The tree shrew is the close relative of primate with a squirrel-like appearance. Given that tree shrews are easy to raise, easy to domesticate, and have a small body size, with a high reproductive rate, furthermore, the metabolism, physiological function, anatomy and genome are similar to human. It had been widely used as a new experimental animal in medical and biological research. The results of recent research showed that the tree shrew is an animal with the potential to reproduce various human diseases, and is expected to replace the primate animal for the study of animal models of human diseases. The animal infection models of rotavirus, hepatitis virus, herpes virus, dengue virus and influenza virus had been successfully established.In this study, two-month old tree shrews were infected with CA16via respiratory infection, to study the characteristics of infection of CA16on infant tree shrews, and explore the feasibility to establish a tree shrew animal model for CA16infection, to replace the primate animal. Daily activities were regularly observed, body temperatures were measured. Blood, feces, throat and tissues samples were regularly collected. The samples were examined via Real-Time fluorescent quantitative PCR and immunohistochemical technique. The changes of immune cells, the viral nucleic acid, antigen localization and histopathology examination were detected, to analyze the infection characteristics of CA16in tree shrews.The tree shrews infected by CA16were no foot and mouth herpes appeared during two weeks, and the behavior, spirit and diet condition were normal, however, the body temperature was increased, the number of white blood cells and lymphocytes were decreased, and the number of neutrophils and monocyte were increased. The change of viral load in feces, throat, blood and tissues were detected; pathological changes were examined in the lung, liver, kidney, brain, spinal cord and muscle; the antigen antibody reaction was detected in lung, liver and brain.In conclusion, the tree shrews can be infected by CA16, although the HFMD symptoms were mild, the pathological changes were detected. This study had made some achievements, and laid the foundation and information to establish the animal model of CA16infection, the tree shrews can be used to study the pathogenesis and vaccine evaluation of CA16infection.