Porcine reproductive and respiratory syndrome virus (PRRSV), a highly infectious virus, causes severe losses in the swine industry by regulating the inflammatory response, inducing tissue damage, suppressing the innate immune response, and promoting persistent infection in hosts. Interleukin-13 (IL-13) is a cytokine that plays a critical role in regulating immune responses and inflammation, particularly in immune-related disorders, certain types of cancer, and numerous bacterial and viral infections; however, the underlying mechanisms of IL-13 regulation during PRRSV infection are not well understood. In this study, we demonstrated that PRRSV infection elevates IL-13 levels in porcine alveolar macrophages. PRRSV enhances mA-methylated RNA levels while reducing the expression of fat mass and obesity associated protein (FTO, an mA demethylase), thereby augmenting IL-13 production. PRRSV nonstructural protein 9 (nsp9) was a key factor for this modulation. Furthermore, we found that the residues Asp567, Tyr586, Leu593, and Asp595 were essential for nsp9 to induce IL-13 production attenuation of FTO expression. These insights delineate PRRSV nsp9’s role in FTO-mediated IL-13 release, advancing our understanding of PRRSV's impact on host immune and inflammatory responses.

中文翻译：

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高致病性 PRRSV 通过非结构蛋白 9 介导的 N6-甲基腺苷脱甲基酶 FTO 抑制来上调 IL-13 的产生

猪繁殖与呼吸综合征病毒（PRRSV）是一种高传染性病毒，通过调节炎症反应、诱导组织损伤、抑制先天免疫反应、促进宿主持续感染，给养猪业造成严重损失。白介素 13 (IL-13) 是一种细胞因子，在调节免疫反应和炎症方面发挥着关键作用，特别是在免疫相关疾病、某些类型的癌症以及许多细菌和病毒感染中；然而，PRRSV 感染期间 IL-13 调节的潜在机制尚不清楚。在这项研究中，我们证明 PRRSV 感染会升高猪肺泡巨噬细胞中的 IL-13 水平。 PRRSV 增强 m6A 甲基化 RNA 水平，同时减少脂肪量和肥胖相关蛋白（FTO，一种 m6A 去甲基化酶）的表达，从而增加 IL-13 的产生。 PRRSV 非结构蛋白 9 (nsp9) 是这种调节的关键因素。此外，我们发现残基 Asp567、Tyr586、Leu593 和 Asp595 对于 nsp9 诱导 FTO 表达的 IL-13 产生减弱至关重要。这些见解描述了 PRRSV nsp9 在 FTO 介导的 IL-13 释放中的作用，加深了我们对 PRRSV 对宿主免疫和炎症反应影响的理解。