Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural Universitygrid.27871.3b, Nanjing, China.
Laboratory of Virology, Faculty of Veterinary Medicine, Ghent Universitygrid.5342.0, Merelbeke, Belgium.
J Virol. 2022 Sep 28;96(18):e0115422. doi: 10.1128/jvi.01154-22. Epub 2022 Sep 8.
Long noncoding RNAs (lncRNAs) have increasingly been recognized as being integral to cellular processes, including the antiviral immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is costly to the global swine industry. To identify PRRSV-related lncRNAs, we performed RNA deep sequencing and compared the profiles of lncRNAs in PRRSV-infected and uninfected Marc-145 cells. We identified a novel lncRNA called MAHAT (maintaining cell morphology-associated and highly conserved antiviral transcript; LTCON_00080558) that inhibits PRRSV replication. MAHAT binds and negatively regulates expression by recruiting and binding DDX6, an RNA helicase forming a complex with . Inhibition of expression results in increased type I interferon expression and decreased PRRSV replication. This finding reveals a novel mechanism by which PRRSV evades the host antiviral innate immune response by downregulating the MAHAT-DDX6-ZNF34 pathway. MAHAT could be a host factor target for antiviral therapies against PRRSV infection. Long noncoding RNAs (lncRNAs) play important roles in viral infection by regulating the transcription and expression of host genes, and interferon signaling pathways. Porcine reproductive and respiratory syndrome virus (PRRSV) causes huge economic losses in the swine industry worldwide, but the mechanisms of its pathogenesis and immunology are not fully understood. Here, a new lncRNA, designated MAHAT, was identified as a regulator of host innate immune responses. MAHAT negatively regulates the expression of its target gene, , by recruiting and binding DDX6, an RNA helicase, forming a complex with . Inhibition of expression increases type I interferon expression and decreases PRRSV replication. This finding suggests that MAHAT has potential as a new target for developing antiviral drugs against PRRSV infection.
长链非编码 RNA（lncRNA）在细胞过程中发挥重要作用，包括抗病毒免疫反应。猪繁殖与呼吸综合征病毒（PRRSV）对全球养猪业造成了巨大的经济损失。为了鉴定与 PRRSV 相关的 lncRNA，我们进行了 RNA 深度测序，并比较了 PRRSV 感染和未感染 Marc-145 细胞的 lncRNA 图谱。我们发现了一种名为 MAHAT（维持细胞形态相关和高度保守的抗病毒转录物；LTCON_00080558）的新型 lncRNA，它可以抑制 PRRSV 的复制。MAHAT 通过招募和结合 RNA 解旋酶 DDX6 来结合和负调控 的表达，DDX6 与 形成复合物。抑制 的表达会导致 I 型干扰素的表达增加和 PRRSV 复制的减少。这一发现揭示了 PRRSV 通过下调 MAHAT-DDX6-ZNF34 通路来逃避宿主抗病毒先天免疫反应的新机制。MAHAT 可能成为针对 PRRSV 感染的抗病毒治疗的宿主因子靶标。
长链非编码 RNA（lncRNA）通过调节宿主基因的转录和表达以及干扰素信号通路，在病毒感染中发挥重要作用。猪繁殖与呼吸综合征病毒（PRRSV）在全球范围内给养猪业造成了巨大的经济损失，但它的发病机制和免疫学机制尚未完全了解。在这里，我们鉴定了一种新的 lncRNA，命名为 MAHAT，它是宿主先天免疫反应的调节因子。MAHAT 通过招募和结合 RNA 解旋酶 DDX6 来负调控其靶基因 的表达，形成与 的复合物。抑制 的表达会增加 I 型干扰素的表达并减少 PRRSV 的复制。这一发现表明，MAHAT 可能成为开发抗 PRRSV 感染的抗病毒药物的新靶标。
