数字农科院2.0

PRRSV promotes bacterial infection by remodeling actin cytoskeleton and cell membrane proteins

文献类型： 外文期刊

作者： Liu, Xiao;Lv, Fang;Zhu, Yanan;Meng, Yinan;Peng, Bo;Zheng, Zifang;Li, Yang;Xu, Lele;Feng, Yingtong;Zhang, Jianwu;Xiao, Shuqi

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关键词： PRRSV;secondary bacterial infection;actin cytoskeleton;ITG alpha 5;FLNA

期刊名称： MBIO

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年卷期： 2025 年

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收录情况： SCIE（2025版）

摘要： Secondary infection is a worldwide problem in the prevention and control of viral infection. Secondary bacterial infection induced by porcine reproductive and respiratory syndrome virus (PRRSV) infection causes enormous economic losses, but the relevant mechanism remains unclear. We found that the infection of Klebsiella pneumoniae or Streptococcus suis type 2 in the lungs of PRRSV-challenged piglets was significantly higher than the controls, and the infection of PRRSV, influenza A virus H1N1 (H1N1), and porcine circovirus type 2 (PCV2) also significantly increased the infection of the bacteria in vitro. Transcriptomic analysis revealed that PRRSV infection significantly altered the expression of cytoskeleton-related proteins, among which the expression of actin-binding protein filamin A (FLNA) was significantly increased, and knockdown of FLNA could significantly reduce bacterial invasion. Mechanistic studies found that FLNA drives actin cytoskeleton rearrangement by promoting F-actin generation, thereby facilitating bacterial invasion. Further studies found that PRRSV promoted bacterial adhesion by upregulating the expression of integrin alpha 5 (ITG alpha 5). ITG alpha 5 could induce actin cytoskeleton rearrangement by promoting FLNA expression, thus aggravating bacterial invasion. Furthermore, we found that lentiviral shRNA-mediated knockdown of FLNA or ITG alpha 5 significantly reduced bacterial infection in the lungs of mice and protected mice from death. These results suggest that the regulation of actin cytoskeleton and cell membrane proteins may be a conserved mechanism of virus-induced secondary bacterial infection.IMPORTANCEAn important reason why porcine reproductive and respiratory syndrome virus (PRRSV) is difficult to control effectively is that it often causes severe secondary bacterial infections, which are usually attributed to the immunosuppression caused by PRRSV. However, the mechanism by which PRRSV infection leads to increased susceptibility of cells to bacterial infection has been largely overlooked. We revealed that PRRSV induced actin cytoskeleton rearrangement by upregulating FLNA expression, thereby aggravating bacterial invasion. PRRSV increased bacterial adhesion by promoting the ITG alpha 5 expression, and the upregulation of ITG alpha 5 could induce FLNA-mediated actin cytoskeleton rearrangement. Furthermore, we found that H1N1 and porcine circovirus type 2 infection also significantly promoted the expression of FLNA and ITG alpha 5 and increased the infection of multiple bacteria. These results suggest that FLNA and ITG alpha 5 play important roles in virus-induced secondary bacterial infection.

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