Coinfection with bacterial pathogens and genetic modification of PRRSV-2 for suppression of NF-κB and attenuation of proinflammatory responses

文献类型： 外文期刊

第一作者： Tang, Junyu

作者： Tang, Junyu;Kim, Jineui;Yoo, Dongwan;Wang, Leyi;Fang, Weihuan;Su, Chia-Ming;Du, Yijun;Kim, Jineui

作者机构：

关键词： PRRS; NF-kappa B; PIAS1; Nucleocapsid; PRDC; Streptococcus suis; Cytokine storm; Coinfection

期刊名称：VIROLOGY （ 影响因子：2.4； 五年影响因子：2.5 ）

ISSN： 0042-6822

年卷期： 2025 年 606 卷

页码：

收录情况： SCI

摘要： Porcine reproductive and respiratory syndrome virus (PRRSV) infects pulmonary alveolar macrophages and induces inflammation in the respiratory system. In swine farms, coinfection with PRRSV and bacterial pathogens is common and can result in clinically complicated outcomes, including porcine respiratory disease complex. Coinfection can cause excessive expressions of proinflammatory mediators and may lead to cytokine-storm-like syndrome. An immunological hallmark of PRRSV-2 is the bidirectional regulation of NF-kappa B with the nucleocapsid (N) protein identified as the NF-kappa B activator. We generated an NF-kappa B-silencing mutant PRRSV-2 by mutating the N gene to block its binding to PIAS1 [protein inhibitor of activated STAT-1 (signal transducer and activator of transcription 1)]. PIAS1 functions as an NF-kappa B repressor, and thus, the PIAS1-binding modified N-mutant PRRSV2 became NF-kappa B activation-resistant in its phenotype. During coinfection of pigs with PRRSV-2 and Streptococcus suis, the N-mutant PRRSV-2 decreased the expression of proinflammatory cytokines and showed clinical attenuation. This review describes the coinfection of pigs with various pathogens, the generation of mutant PRRSV for NF-kappa B suppression, inflammatory profiles during bacterial coinfection, and the potential application of these findings to designing a new vaccine candidate for PRRSV-2.

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