Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences (College of Bee Science), Fujian Agricultural and Forestry University, Fuzhou 350002, China.
College of JIN SHAN, Fujian Agricultural and Forestry University, Fuzhou 350002, China.
Int J Mol Sci. 2022 Mar 18;23(6):3306. doi: 10.3390/ijms23063306.
Pseudorabies virus (PRV) infection could cause severe histopathological damage via releasing multiple factors, including cytokines, peptides, etc. Here, peptidomic results showed that 129 peptides were identified in PRV-infected mouse lungs and were highly involved in the process of PRV infection. The role of one down-regulated biological peptide (designated as AGDP) during PRV infection was investigated. To verify the expression profiles of AGDP in response to PRV infection, the expression level of the precursor protein of AGDP mRNA was significantly decreased in PRV-infected mouse lungs and cells. The synthesized AGDP-treating cells were less susceptible to PRV challenges than the controls, as demonstrated by the decreased virus production and gE expression. AGDP not only inhibited the expression of TNF-α and IL-8 but also appeared to suppress the extracellular release of high-mobility group box 1 (HMGB1) by inhibiting the output of nuclear HMGB1 in cells. AGDP could also inhibit the degradation of IκBα and the phosphorylation levels of P65 after PRV infection. In total, our results revealed many meaningful peptides involved in PRV infection, thereby enhancing the current understanding of the host response to PRV infection, and how AGDP may serve as a promising candidate for developing novel anti-PRV drugs.
伪狂犬病毒(PRV)感染可通过释放多种因子(包括细胞因子、肽等)引起严重的组织病理学损伤。在这里,肽组学结果显示,在 PRV 感染的小鼠肺部中鉴定出 129 种肽,这些肽高度参与 PRV 感染过程。研究了 PRV 感染过程中一种下调的生物肽(命名为 AGDP)的作用。为了验证 AGDP 在 PRV 感染中的表达谱,AGDP 前体蛋白 mRNA 的表达水平在 PRV 感染的小鼠肺部和细胞中显著降低。与对照组相比,用合成的 AGDP 处理的细胞对 PRV 挑战的敏感性降低,表现为病毒产量和 gE 表达降低。AGDP 不仅抑制了 TNF-α 和 IL-8 的表达,而且似乎通过抑制细胞内核 HMGB1 的输出来抑制高迁移率族蛋白 B1(HMGB1)的细胞外释放。AGDP 还可以抑制 PRV 感染后 IκBα 的降解和 P65 的磷酸化水平。总的来说,我们的结果揭示了许多参与 PRV 感染的有意义的肽,从而增强了对宿主对 PRV 感染反应的现有理解,以及 AGDP 如何可作为开发新型抗 PRV 药物的有前途的候选物。