| 1. Background and ObjectHuman Enterovirus 71(EV71) is one of the most important pathogens of neurotoxicity. Hand,foot and mouth disease(HFMD) is a viral infectious disease caused by EV71,with severe complications of serious disease of the central nervous system,cardiorespiratory failure and even death in children.Therefore, it is a great significance to insight multiple organs infection and the mechanisms of lung injury by EV71. The object in this report is to study the distribution and prevalence of EV71 receptor in different organs in human for providing the molecular basis to explore EV71 infected target cells and organs. Also, the pathological changes of EV71 infection and the distribution of EV71 virus antigen in children with death autopsy specimens were observed and detected. These results might provide novel strategy for exploring EV71 infection in multiple organs and tissues especially the possible mechanism of lung injury.2. Methods2.1 The distribution of EV71 receptors (PSGL-1, SCARB2) in human were detected using immunohistochemical analysis.2.1 Pathological features of 11 cases of systematic autopsy tissues from the patient with fatal EV71 were studied by light microscopy.2.3 The distribution of EV71 virus antigen in the 11 cases of full autopsy tissue samples from the patient with fatal EV71 were analyed by immunohistochemistry.3. Results3.1 The distribution EV71 receptor in HumanBoth Human P-selectin glycoprotein ligand-1 (PSGL-1) and Scavenger receptor classB, member2 (SCARB2) were expressed in human. Distribution of PSGL-1 was mainly detected in the human central nervous system, especially brainstem, also distributed in the larynx, trachea, bronchus, bronchiole and alveolar cells of respiratory tract and the epithelial cells of the intestinal tract in the digestive tract. Distribution of SCARB2 receptors are mainly detected in the central nervous system, respiratory tract and digestive tract.3.2 The pathological characteristics of EV71 infection in severe infant11 cases showed predominant changes in central system, with encephalitis identified mainly in brainstem. Histologic findings included neuronal degeneration and necrosis, neuronophagia, perivascular cuffing and diffuse or nodular hyperplasia of macrophages/microglia. The larynx, trachea, bronchi and bronchioles showed inflammation. Tube wall surrounded lymph cells, mononuclear cells and other inflammatory cell diffuse or focal infiltration. Alveolar septal thicken and inflammatory cell infiltration and pulmonary congestion, pulmonary edema and focal hemorrhage. The intestinal wall became thinner, mucosal hyperemia, erosion, infiltration of inflammatory cells and submucosal lymphoid follicular hyperplasia.3.3 The distribution of virus antigen in tissues and organs of patients with infected EV71Central nervous system neurons and glial cells showed virus antigen positive, predominated in the brainstem, followed by the cerebrum and cerebellum, suggesting that the nerve cells and glial cells are the main attacked target cells. In respiratory system, the laryngeal, tracheal, bronchial and bronchiolar epithelial cells were positive, but a small amount of positive cells, suggest that airway epithelial cells were also EV71 attack target cells. EV71 antigen in intestinal epithelial is positive.4. Conclusion:4.1 EV71 receptor was expressed in the central nervous system, respiratory system and digestive system, suggesting that these systems were probably the target organ of EV71 virus infection.4.2 EV71 might cause a disseminated infection and multi-organ damages, which were predominant in central nervous system, respiratory system and digestive system.4.3 Fatal EV71 infection is systemic diseases, which mainly involves the central nervous system and respiratory system. The brain stem and the respiratory tract were the target of EV71.4.4 Lung injury caused by EV71,in addition to neurogenic, the virus can spread to the lung tissue from the upper respiratory tract or viruses infected directly alveolar cells. |
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