PDF(Pubmed)
Abstract：
Hepatitis E virus (HEV) has become one of the important pathogens that threaten the global public health. Type 3 and 4 HEV are zoonotic, which can spread vertically and cause placental damage. At the same time, autophagy plays an important role in the process of embryo development and pregnancy maintenance. However, the relationship between HEV and autophagy, especially in the placenta tissue, has not been clarified. We found lower litter rates in HEV-infected female mice, with significant intrauterine abortion of the embryo (24.19%). To explore the effects of HEV infection on placenta autophagy, chorionic cells (JEG-3) and mice placenta have been employed as research objects, while the expression of autophagy-related proteins (ATGs) has been detected in JEG-3 cells with different times of HEV inoculation. The results demonstrated that the expression of protein LC3 decreased and p62 accumulated, meanwhile ATGs such as ATG4B, ATG5, and ATG9A in JEG-3 cells have decreased significantly. In addition, the maturation of autophagosomes, which referred to the process of the combination of autophagosomes and lysosomes was prevented by HEV infection as well. All processes of autophagic flux, which include the initiation, development, and maturation three stages, were suppressed in JEG-3 cells after HEV infection. Similarly, the protein and gene expression of LC3 were significantly decreased in the placenta of pregnant mice with HEV infection. In summary, our results suggested that HEV inhibited autophagy in JEG-3 cells and placenta of pregnant mice, which might be the important pathogenic mechanisms of HEV infection leading to embryo abortion.
摘要：
戊型肝炎病毒(HEV)已成为威胁全球公共卫生的重要病原体之一。3型和4型HEV是人畜共患的，可以垂直传播并导致胎盘损伤。同时,自噬在胚胎发育和妊娠维持过程中起着重要作用。然而,HEV与自噬的关系,尤其是在胎盘组织中，尚未澄清。我们发现感染HEV的雌性小鼠产仔率较低，有明显的胚胎宫内流产（24.19%）。探讨HEV感染对胎盘自噬的影响,以绒毛膜细胞(JEG-3)和小鼠胎盘为研究对象,而在不同的HEV孵育时间的JEG-3细胞中检测到自噬相关蛋白（ATGs）的表达。结果表明，LC3蛋白的表达降低，p62积累，同时ATG4B等ATGG，ATG5、ATG9A在JEG-3细胞中都有显著降低。此外,自噬体的成熟，这是指自噬体和溶酶体结合的过程，也可以通过HEV感染来预防。自噬通量的所有过程，其中包括启动，发育和成熟三个阶段，HEV感染后JEG-3细胞受到抑制。同样，妊娠合并HEV小鼠胎盘中LC3蛋白和基因表达显著降低。总之,我们的结果表明，HEV抑制JEG-3细胞和孕鼠胎盘的自噬，这可能是HEV感染导致胚胎流产的重要致病机制。
