Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China.
Key Laboratory of Applied Technology On Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics & Advanced Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology & College of Veterinary Medicine of Zhejiang, A&F University, Lin'an District, 666 Wusu StreetZhejiang Province, Hangzhou, 311300, China.
Cell Stress Chaperones. 2023 Jan;28(1):49-60. doi: 10.1007/s12192-022-01300-1. Epub 2022 Nov 28.
Bovine viral diarrhea (BVD) is a worldwide infectious disease caused by bovine viral diarrhea virus (BVDV) infection, which invades the placenta, causes abortion, produces immune tolerance and continuously infects calves, and causes huge economic losses to the cattle industry. The endoplasmic reticulum (ER) is an important organelle in cells, which is prone to ER stress after being stimulated by pathogens, thus activating the ER stress-related apoptosis. Studies have confirmed that BVDV can utilize the ER of its host to complete its own proliferation and stimulate ER stress to a certain extent. However, the role of ER stress in BVDV infecting bovine placental trophoblast cells (BTCs) and inducing apoptosis is still unclear. We are using the cytopathic strain of BVDV (OregonC24Va), which can cause apoptosis of BTCs, as a model system to determine how ER stress induced by BVDV affects placental toxicity. We show that OregonC24Va can infect BTCs and proliferate in it. With the proliferation of BVDV in BTCs, ER stress-related apoptosis is triggered. The ER stress inhibitor 4-PBA was used to inhibit the ER stress of BTCs, which not only inhibited the proliferation of BVDV, but also reduced the apoptosis of BTCs. The ER stress activator Tg can activate ER stress-related apoptosis, but the proliferation of BVDV does not change in BTCs. Therefore, BVDV utilizes the UPR of activated ER stress to promote the proliferation of BVDV in the early stage of infection, and activates the ER stress-related apoptosis of BTCs in the later stage with the virus proliferation to promote the cell apoptosis and further spread of the virus. Our research provides a new theoretical basis for exploring the placental infection and vertical transmission of BVDV.
牛病毒性腹泻（BVD）是一种由牛病毒性腹泻病毒（BVDV）感染引起的全球性传染病，它会侵袭胎盘，导致流产，产生免疫耐受，并持续感染牛犊，给牛业造成巨大的经济损失。内质网（ER）是细胞中的一个重要细胞器，受到病原体刺激后容易发生 ER 应激，从而激活与 ER 应激相关的细胞凋亡。研究证实，BVDV 可以利用宿主的 ER 来完成自身的增殖，并在一定程度上刺激 ER 应激。然而，ER 应激在 BVDV 感染牛胎盘滋养层细胞（BTCs）并诱导凋亡中的作用尚不清楚。我们正在使用可以引起 BTCs 凋亡的致细胞病变型 BVDV（OregonC24Va）作为模型系统，来确定 BVDV 诱导的 ER 应激如何影响胎盘毒性。我们发现 OregonC24Va 可以感染 BTCs 并在其中增殖。随着 BVDV 在 BTCs 中的增殖，会引发与 ER 应激相关的凋亡。用 ER 应激抑制剂 4-PBA 抑制 BTCs 的 ER 应激，不仅抑制了 BVDV 的增殖，还减少了 BTCs 的凋亡。ER 应激激活剂 Tg 可以激活与 ER 应激相关的凋亡，但 BTCs 中的 BVDV 增殖没有变化。因此，BVDV 在感染的早期利用激活的 ER 应激的 UPR 促进 BVDV 的增殖，在后期随着病毒的增殖激活与 ER 应激相关的 BTCs 凋亡，促进细胞凋亡和病毒的进一步传播。我们的研究为探索 BVDV 的胎盘感染和垂直传播提供了新的理论依据。
