State Key Laboratory of Veterinary Etiological Biology and OIE/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institutegrid.454892.6, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
J Virol. 2021 Nov 9;95(23):e0112021. doi: 10.1128/JVI.01120-21. Epub 2021 Sep 15.
Foot-and-mouth disease virus (FMDV) infection in cloven-hoofed animals causes severe inflammatory symptoms, including blisters on the oral mucosa, hoof, and breast; however, the molecular mechanism underlying the inflammatory response is unclear. In this study, we provide the first evidence that the FMDV protein VP3 activates lipopolysaccharide-triggered Toll-like receptor 4 (TLR4) signaling. FMDV VP3 increased the expression of TLR4 by downregulating the expression of the lysozyme-related protein Rab7b. Additionally, Rab7b can interact with VP3 to promote the replication of FMDV. Our findings suggested that VP3 regulates the Rab7b-TLR4 axis to mediate the inflammatory response to FMDV. Foot-and-mouth disease virus (FMDV) infection causes a severe inflammatory response in cloven-hoofed animals, such as pigs, cattle, and sheep, with typical clinical manifestations of high fever, numerous blisters on the oral mucosa, hoof, and breast, as well as myocarditis (tigroid heart). However, the mechanism underlying the inflammatory response caused by FMDV is enigmatic. In this study, we identified the VP3 protein of FMDV as an important proinflammatory factor. Mechanistically, VP3 interacted with TLR4 to promote TLR4 expression by inhibiting the expression of the lysozyme-related protein Rab7b. Our findings suggest that FMDV VP3 is a major proinflammatory factor in FMDV-infected hosts.
口蹄疫病毒（FMDV）感染偶蹄动物会引起严重的炎症症状，包括口腔黏膜、蹄和乳房上的水疱；然而，炎症反应的分子机制尚不清楚。在本研究中，我们首次提供证据表明，FMDV 蛋白 VP3 激活了脂多糖触发的 Toll 样受体 4（TLR4）信号。FMDV VP3 通过下调溶菌酶相关蛋白 Rab7b 的表达来增加 TLR4 的表达。此外，Rab7b 可以与 VP3 相互作用，促进 FMDV 的复制。我们的研究结果表明，VP3 通过调节 Rab7b-TLR4 轴来介导 FMDV 引起的炎症反应。
口蹄疫病毒（FMDV）感染引起猪、牛和羊等偶蹄动物严重的炎症反应，具有高热、口腔黏膜、蹄和乳房上出现大量水疱以及心肌炎（虎斑心）等典型临床症状。然而，FMDV 引起的炎症反应的机制尚不清楚。在本研究中，我们确定了 FMDV 的 VP3 蛋白是一种重要的促炎因子。从机制上讲，VP3 通过抑制溶菌酶相关蛋白 Rab7b 的表达，与 TLR4 相互作用来促进 TLR4 的表达。我们的研究结果表明，FMDV VP3 是 FMDV 感染宿主中的主要促炎因子。
