Department of Biochemistry, Rush University, Cohn Research Building, 1735 W, Harrison Street, Chicago, IL 60612, USA.
Gut Pathog. 2013 Aug 7;5(1):22. doi: 10.1186/1757-4749-5-22.
Human rotavirus (HRV) is the most important cause of severe diarrhea in infants and young children. Probiotic Lactobacillus rhamnosus GG (LGG) reduces rotavirus infection and diarrhea. However, the molecular mechanisms of LGG-mediated protection from rotavirus infection are poorly understood. Autophagy plays an essential role in responses to microbial pathogens. However, the role of autophagy in HRV infection and LGG treatment is unknown. We hypothesize that rotavirus gastroenteritis activates autophagy and that LGG suppresses virus-induced autophagy and prevents intestinal damage in infected piglets.
We used LGG feeding to combat viral gastroenteritis in the gnotobiotic pig model of virulent HRV infection.
We found that LGG feeding did not increase autophagy, whereas virus infection induced autophagy in the piglet intestine. Virus infection increased the protein levels of the autophagy markers ATG16L1 and Beclin-1 and the autophagy regulator mTOR. LGG treatment during viral gastroenteritis reduced autophagy marker expression to normal levels, induced apoptosis and partially prevented virus-induced tissue damage.
Our study provides new insights into virus-induced autophagy and LGG suppression of uncontrolled autophagy and intestinal injury. A better understanding of the antiviral activity of LGG will lead to novel therapeutic strategies for infant infectious diseases.
人类轮状病毒（HRV）是导致婴幼儿严重腹泻的最重要原因。益生菌鼠李糖乳杆菌 GG（LGG）可减少轮状病毒感染和腹泻。然而，LGG 介导的抗轮状病毒感染的分子机制尚不清楚。自噬在应对微生物病原体的反应中起着至关重要的作用。然而，自噬在 HRV 感染和 LGG 治疗中的作用尚不清楚。我们假设轮状病毒肠胃炎会激活自噬，而 LGG 会抑制病毒诱导的自噬，并防止感染仔猪的肠道损伤。
我们使用 LGG 喂养来对抗在强毒 HRV 感染的无菌猪模型中的病毒性肠胃炎。
我们发现 LGG 喂养不会增加自噬，而病毒感染会诱导仔猪肠道中的自噬。病毒感染增加了自噬标记物 ATG16L1 和 Beclin-1 的蛋白水平以及自噬调节剂 mTOR。在病毒性肠胃炎期间，LGG 处理将自噬标记物的表达降低至正常水平，诱导细胞凋亡并部分防止病毒引起的组织损伤。
我们的研究为病毒诱导的自噬和 LGG 抑制不受控制的自噬和肠道损伤提供了新的见解。更好地了解 LGG 的抗病毒活性将为婴儿传染病的治疗提供新的策略。
