The Effect Of Hepatitis E Virus Infection On Intestinal Mucosal Immunity

In order to reveal the interaction between Hepatitis E virus (HEV) and intestine, we used New Zealand white rabbits and gerbils to study the effect of HEV on intestinal mucosal immune and the location of HEV antigen in the gut. Histopathology, histocytochemistry, immunohistochemistry and PCR methods were used to analyze the effect of HEV on intestine structure, and quantify the intestinal mucosal immune cells and relevant factors. The results revealed the relationship between intestinal immune cells and local mucosal immune function during the process of HEV invasion.1After the infection of rabbits with HEV through intraperitoneal injection, the rabbits showed different infection types. HEV RNA can be detected in the serum and fecea, and HEV ORF2antigen can be detected in serum. While the liver also showed similar pathological changes with human HEV. HEV RNA and ORF2antigen in rabbits were distributed in the different tissues and organs in rabbits after infection. At the same time, HEV antigen was positive in the gut and gut-associated lymphoid tissue when HEV RNA was existed in feces. HEV ORF2antigen was mainly existed in the cytoplasm of intestine epithelial cells and M cells of sacculus and appendix. While HEV ORF3antigen was largely distributed in cytoplasm intestine epithelial cells, but granularly distributed in luminal surface of the follicular associated epithelial cells and within few monocytes in lymphoid tissues.2After infected swine HEV, the feces and intestine tissues can be detected HEV RNA positive in all gerbils at different time after inoculation. HEV ORF2antigen was positive in the intestine, and the positive signals were mainly distributed in the cytoplasm of epithelial cells and glandular epithelium. The observation of gerbils intestinal morphology showed that the structure was normal, the numbers of goblet cells was not increased significantly after HEV infection. But the length of intestinal villi, the depth of crypt was decreased at7days and14days post inoculation, while rebounded at21days and28days post inoculation. Immunohistochemistry for laminin showed that the basic membrane structure was not changed.The data of mucosal immune showed that the number of Payer’s patch and intraepithelial cells was increased but not significantly. The total number of mast cells was increased significantly at21days and28days post inoculation. The IgA expression was elevated significantly at each time post inoculation, and the numbers of dendritic cells in intestinal lamina propria increased at21and28days after infection, especially at21days.3After inoculating ligated intestine in vivo in rabbits, HEV ORF2antigen in ileum and sacculus was positive, furthermore, the positive signal of HEV ORF2antigen was stronger at30min than10min after inoculation. The positive signals were mainly distributed in the intestine epithelial cells, sacculus dome epithelium and few monocytes at lymphoid tissue. The lymphocyte stimulation index in sacculus was increased significantly in rabbits at24h after inoculation. When pretreated with IgA antibody, the HEV ORF2antigen in sacculus was not varied obviously, but the expression of HEV antigens in ileum mucosal epithelial surface was increased a lot. The results above showed that HEV could interact directly with intestine. The HEV RNA and HEV antigens were distributed in each segment of intestine and gut-associated lymphoid tissue. At the same time, the infection of HEV could affect the intestine structure and mucosal immune function, especially increase the expression of IgA and the amount of mast cells and dendritic cells.