[Animal Modeling] - Establishment of a Tree Shrew Hand, Foot, and Mouth Disease Model

  Coxsackie virus A16 (CA16) is commonly considered one of the main pathogens of human hand, foot, and mouth disease. The clinical manifestations of hand, foot, and mouth disease in young children include small vesicles in the hands, feet, and mouth, as well as severe inflammatory central nervous system damage. In this study, experimental infection of tree shrews with CA16 was used to investigate the pathogenesis of CA16.

  Experimental animals: 15 healthy female tree shrews (80+10g, 2-month old) were randomly divided into an infection group (n=12) and a simulated infection control group (n=3). All experimental procedures were approved by the Yunnan Provincial Laboratory Animal Management Office, and all animals were raised separately according to the guidelines and policies of the Experimental Animal Committee (CMAS) of the Biomedical Research Institute of the Chinese Academy of Medical Sciences. All individuals have previously demonstrated the absence of CA16 antibodies through neutralization tests.

  Experimental method: The tree shrews in the experimental group were infected with CA16 (104.5 CCID50) from the respiratory tract by nasal spray, and the control group was simulated by normal saline spray, which was an uninfected negative control. Monitor tree shrews daily and measure rectal temperature using a digital thermometer stick (MCBOMR, Omron) 2 days after infection. At the same time, take EDTA coated capillary vein blood samples for routine biological viral load testing (Veterinary Multispecies Blood System, Hemavet950FS, Deloitte Technology Co., Ltd.), Pathogenic and histopathological tests of all tissues and organs were conducted on the 4th, 7th, 10th, and 14th days after the tree shrew was anesthetized and executed.

  The results showed that the body temperature and the percentage of neutrophils and monocytes in the blood of tree shrews infected with CA16 increased from 4 to 7 days after infection. The dynamic distribution of CA16 in different tissues and feces can be found at various stages of infection, and pathological changes in the central nervous system and other organs can also be observed. This study indicates that tree shrews can serve as a good animal model for studying CA16 infection.