Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important viral pathogens in the swine industry. Current antiviral strategies do not effectively prevent and control PRRSV. Recent reports show that microRNAs (miRNAs) play vital roles in viral infections by post transcriptionally regulating the expression of viral or host genes. Our previous research showed that non-muscle myosin heavy chain 9 (MYH9) is an essential factor for PRRSV infection. Using bioinformatic prediction and experimental verification, we demonstrate that MYH9 expression is regulated by the miRNA let-7f-5p, which binds to the MYH9 mRNA 3′UTR and may play an important role during PRRSV infection. To understand how let-7f-5p regulates PRRSV infection, we analyzed the expression pattern of both let-7f-5p and MYH9 in porcine alveolar macrophages (PAMs) after infection with either highly pathogenic PRRSV (HP-PRRSV) or classical type PRRSV (N-PRRSV) using a deep sequencing approach with quantitative real-time PCR validation. Our results showed that both HP-PRRSV and N-PRRSV infection reduced let-7f-5p expression while also inducing MYH9 expression. Furthermore, let-7f-5p significantly inhibited PRRSV replication through suppression of MYH9 expression. These findings not only provide new insights into the pathogenesis of PRRSV, but also suggest potential new antiviral strategies against PRRSV infection.
Highlights
Porcine reproductive and respiratory syndrome (PRRS) is one of the most highly infectious swine diseases[1], resulting in great economic losses every year affecting the swine industry worldwide[2]
Using bioinformatics prediction and experimental verification, we demonstrate that overexpression of let-7f-5p inhibits Porcine reproductive and respiratory syndrome virus (PRRSV) replication in porcine alveolar macrophages (PAMs) by targeting myosin heavy chain 9 (MYH9) sequences
We found that one pig miRNA and three monkey miRNAs exhibited potential 3′UTR binding sites to pig and monkey MYH9 messenger RNAs (mRNAs), respectively
Summary
Porcine reproductive and respiratory syndrome (PRRS) is one of the most highly infectious swine diseases[1], resulting in great economic losses every year affecting the swine industry worldwide[2]. Our previous work demonstrated that MYH9 guides the infection process after virus particles attach to cell surface receptors, culminating in completion of subsequent un-coating events required for PRRSV genomic release within the host cell[15]. MicroRNAs have been reported to modulate PRRSV infection and replication in multiple ways, by targeting cellular genes essential for virus replication or directly targeting viral genomic sequences. Our previous work demonstrated that miR-24-3p suppressed cellular HO-1 expression, it concurrently promoted PRRSV replication[20] Both miR-181 targeting of viral genomic RNA and cellular receptor CD163 have been implicated in the suppression of PRRSV replication[21]. While miR-26 inhibits PRRSV replication by upregulating type I interferons[22], miR-125b inhibits PRRSV replication by negatively regulating the NF-κB pathway[23]
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