Research Laboratory for Immunity Enhancement in Humans and Domestic Animals, Program of Biotechnology, Faculty of Science, Maejo University, Chiang Mai, 50290, Chiang Mai, Thailand.
BMC Vet Res. 2024 Aug 3;20(1):344. doi: 10.1186/s12917-023-03760-8.
Porcine reproductive and respiratory syndrome virus (PRRSV) induces a poor innate immune response following infection. This study evaluates the effects of transforming growth factor beta 1 (TGFβ1) up-regulated by PRRSV on gene expressions of co-stimulatory molecules, type I interferon (IFN), type I IFN-regulated genes (IRGs), pattern recognition receptors, and pro-inflammatory cytokines in PRRSV-inoculated monocyte-derived macrophages (MDMs). Phosphorothioate-modified antisense oligodeoxynucleotides (AS ODNs) specific to various regions of porcine TGFβ1 mRNA were synthesized, and those specific to the AUG region efficiently knockdown TGFβ1 mRNA expression and protein translation. Transfection of TGFβAS ODNs in MDMs inoculated with either classical PRRSV-2 (cPRRSV-2) or highly pathogenic PRRSV-2 (HP-PRRSV-2) significantly reduced TGFβ1 mRNA expression and significantly increased mRNA expressions of CD80, CD86, IFNβ, IRGs (i.e. IFN regulatory factor 3 (IRF3), IRF7, myxovirus resistance 1, osteopontin, and stimulator of IFN genes), Toll-like receptor 3, and tumor necrosis factor-alpha. Transfection of TGFβAS ODNs in MDMs inoculated with HP-PRRSV-2 also significantly increased mRNA expressions of IFNα, IFNγ, and 2'-5'-oligoadenylate synthetase 1. The quantity of PRRSV-2 RNA copy numbers was significantly reduced in MDMs transfected with TGFβAS ODNs as compared to untransfected MDMs. Recombinant porcine TGFβ1 (rTGFβ1) and recombinant porcine IFNα (rIFNα) sustained and reduced the yields of PRRSV-2 RNA copy numbers in PRRSV-2 inoculated MDMs, respectively. These findings demonstrate a strategy of PRRSV for innate immune suppression via an induction of TGFβ expression. These findings also suggest TGFβ as a potential parameter that future PRRSV vaccine and vaccine adjuvant candidates should take into consideration.
猪繁殖与呼吸综合征病毒（PRRSV）感染后会诱导先天免疫应答不良。本研究评估了 PRRSV 上调的转化生长因子β 1（TGFβ1）对 PRRSV 感染的单核细胞衍生巨噬细胞（MDM）中共刺激分子、I 型干扰素（IFN）、I 型 IFN 调节基因（IRG）、模式识别受体和促炎细胞因子基因表达的影响。合成了针对猪 TGFβ1 mRNA 不同区域的硫代磷酸修饰反义寡脱氧核苷酸（AS ODN），针对 AUG 区域的 AS ODN 可有效降低 TGFβ1 mRNA 表达和蛋白翻译。在接种经典 2 型猪繁殖与呼吸综合征病毒（cPRRSV-2）或高致病性 2 型猪繁殖与呼吸综合征病毒（HP-PRRSV-2）的 MDM 中转染 TGFβAS ODN 可显著降低 TGFβ1 mRNA 表达，显著增加 CD80、CD86、IFNβ、IRG（IRF3、IRF7、抗流感病毒蛋白 1、骨桥蛋白和 IFN 基因刺激物）、Toll 样受体 3 和肿瘤坏死因子-α的 mRNA 表达。在接种 HP-PRRSV-2 的 MDM 中转染 TGFβAS ODN 还显著增加了 IFNα、IFNγ和 2′-5′寡聚腺苷酸合成酶 1 的 mRNA 表达。与未转染的 MDM 相比，转染 TGFβAS ODN 的 MDM 中 PRRSV-2 RNA 拷贝数明显减少。重组猪 TGFβ1（rTGFβ1）和重组猪 IFNα（rIFNα）分别维持和降低 PRRSV-2 接种的 MDM 中 PRRSV-2 RNA 拷贝数的产量。这些发现表明 PRRSV 通过诱导 TGFβ 表达来抑制先天免疫。这些发现还表明 TGFβ 可作为未来 PRRSV 疫苗和疫苗佐剂候选物应考虑的潜在参数。
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