J Agric Food Chem. 2018 Nov 7;66(44):11757-11766. doi: 10.1021/acs.jafc.8b04704. Epub 2018 Oct 30.
Porcine circovirus type 2 (PCV2) is an important pathogen in swine herds. We previously reported that glutamine (Gln) deficiency promoted PCV2 infection in vitro. Here, we established a Gln deficiency model in vivo and further investigated the detailed molecular mechanisms. In vivo and in vitro, Gln deficiency promoted PCV2 infection, which was evident through increased viral yields and PCV2 Cap protein synthesis. It also induced autophagy, as demonstrated by the increases in LC3-II conversion, SQSTM1 degradation, and GFP-LC3 dot accumulation. Autophagy inhibition abolished the effects of Gln deficiency on PCV2 infection. Inhibition of ROS generation alleviated the Gln deficiency-activated JAK2/STAT3 signaling pathway, thereby inhibiting autophagy induction. In vitro, the inhibition of STAT3 by an inhibitor or RNA interference blocked autophagy, thus reversing the effects of Gln deficiency on PCV2 infection. These results indicate that Gln deficiency activates autophagy by upregulating ROS-medicated JAK2/STAT3 signaling and thereby promoting PCV2 infection.
猪圆环病毒 2 型（PCV2）是猪群中的一种重要病原体。我们之前报道过谷氨酰胺（Gln）缺乏会促进 PCV2 的体外感染。在这里，我们建立了体内 Gln 缺乏模型，并进一步研究了详细的分子机制。在体内和体外，Gln 缺乏促进了 PCV2 的感染，这表现在病毒产量和 PCV2 Cap 蛋白合成的增加上。它还诱导了自噬，这可以通过 LC3-II 转化、SQSTM1 降解和 GFP-LC3 斑点积累的增加来证明。自噬抑制消除了 Gln 缺乏对 PCV2 感染的影响。ROS 生成的抑制缓解了 Gln 缺乏激活的 JAK2/STAT3 信号通路，从而抑制了自噬的诱导。在体外，通过抑制剂或 RNA 干扰抑制 STAT3 阻断了自噬，从而逆转了 Gln 缺乏对 PCV2 感染的影响。这些结果表明，Gln 缺乏通过上调 ROS 介导的 JAK2/STAT3 信号来激活自噬，从而促进 PCV2 的感染。
