Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to the global swine industry. The emergence of new, highly virulent strains has precipitated recurrent outbreaks worldwide, underscoring the ongoing battle between host and virus. Thus, there is an imperative to formulate a more comprehensive and effective disease control strategy. Studies have shown that host non-coding RNA (ncRNA) is an important regulator of host - virus interactions in PRRSV infection. Hence, a thorough comprehension of the roles played by ncRNAs in PRRSV infection can augment our understanding of the pathogenic mechanisms underlying PRRSV infection. This review focuses on elucidating contemporary insights into the roles of host microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in PRRSV infection, providing both theoretical foundations and fresh perspectives for ongoing research into the mechanisms driving PRRSV infection and its pathogenesis.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly infectious agent that poses a significant economic threat to the global swine industry. Efficient viral entry relies on interactions with cellular receptors, with CD163-a cysteine-rich scavenger receptor found on porcine alveolar macrophages (PAMs)-playing a critical role. Extensive evidence supports CD163's essential function in PRRSV infection. This review synthesizes current knowledge about CD163's role, examining its structure-function relationship and identifying specific regions crucial for viral entry. We evaluate the established role of CD163 in PRRSV pathogenesis and highlight areas requiring further investigation, along with the potential for targeted therapeutic interventions. Understanding the molecular determinants of CD163's function is vital for developing effective strategies to control PRRSV infection and mitigate its economic impact on swine production. Further research into the PRRSV-CD163 interactions will be crucial for creating novel antiviral strategies.

Porcine reproductive and respiratory syndrome (PRRS) caused by porcine reproductive and respiratory syndrome virus (PRRSV) causes considerable economic losses to the global swine industry every year and seriously hinders the healthy development of this industry. Although tremendous efforts have been made over the past 30 years toward the development of prevention and control strategies against PRRSV infection, to date, treatments with proven efficacy have yet to be available due to our incomplete understanding of the molecular basis and complexity of the infection machinery. This review systematically discusses recent advances in the research and development of anti-PRRSV therapies targeting different stages of the viral life cycle. Furthermore, this review puts forward novel intervention targets and research approaches based on our in-depth exploration of virus-host interactions and the latest biological technologies, which have the potential to complement or transform current anti-PRRSV strategies and become breakthrough points for the control of PRRS in the future.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most globally devastating viruses threatening the swine industry worldwide. Substantial advancements have been achieved in recent years towards comprehending the pathogenesis of PRRSV infection and the host response, involving both innate and adaptive immune responses. Not only a multitude of host proteins actively participate in intricate interactions with viral proteins, but microRNAs (miRNAs) also play a pivotal role in the host response to PRRSV infection. If a PRRSV-host interaction at the protein level is conceptualized as the front line of the battle between pathogens and host cells, then their fight at the RNA level resembles the hidden front line. miRNAs are endogenous small non-coding RNAs of approximately 20-25 nucleotides (nt) that primarily regulate the degradation or translation inhibition of target genes by binding to the 3'-untranslated regions (UTRs). Insights into the roles played by viral proteins and miRNAs in the host response can enhance our comprehensive understanding of the pathogenesis of PRRSV infection. The intricate interplay between viral proteins and cellular targets during PRRSV infection has been extensively explored. This review predominantly centers on the contemporary understanding of the host response to PRRSV infection at the RNA level, in particular, focusing on the twenty-six miRNAs that affect viral replication and the innate immune response.

Pigs play important roles in agriculture and bio-medicine; however, porcine viral infections have caused huge losses to the pig industry and severely affected the animal welfare and social public safety. During viral infections, many non-coding RNAs are induced or repressed by viruses and regulate viral infection. Many viruses have, therefore, developed a number of mechanisms that use ncRNAs to evade the host immune system. Understanding how ncRNAs regulate host immunity during porcine viral infections is critical for the development of antiviral therapies. In this review, we provide a summary of the classification, production and function of ncRNAs involved in regulating porcine viral infections. Additionally, we outline pathways and modes of action by which ncRNAs regulate viral infections and highlight the therapeutic potential of artificial microRNA. Our hope is that this information will aid in the development of antiviral therapies based on ncRNAs for the pig industry.

Exosomes are biological vesicles secreted and released by cells that act as mediators of intercellular communication and play a unique role in virus infection, antigen presentation, and suppression/promotion of body immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most damaging pathogens in the pig industry and can cause reproductive disorders in sows, respiratory diseases in pigs, reduced growth performance, and other diseases leading to pig mortality. In this study, we used the PRRSV NADC30-like CHsx1401 strain to artificially infect 42-day-old pigs and isolate serum exosomes. Based on high-throughput sequencing technology, 305 miRNAs were identified in serum exosomes before and after infection, among which 33 miRNAs were significantly differentially expressed between groups (13 relatively upregulated and 20 relatively downregulated). Sequence conservation analysis of the CHsx1401 genome identified 8 conserved regions, of which a total of 16 differentially expressed (DE) miRNAs were predicted to bind to the conserved region closest to the 3' UTR of the CHsx1401 genome, including 5 DE miRNAs capable of binding to the CHsx1401 3' UTR (ssc-miR-34c, ssc-miR-375, ssc-miR-378, ssc-miR-486, ssc-miR-6529). Further analysis revealed that the target genes of differentially expressed miRNAs were widely involved in exosomal function-related and innate immunity-related signaling pathways, and 18 DE miRNAs (ssc-miR-4331-3p, ssc-miR-744, ssc-miR-320, ssc-miR-10b, ssc-miR-124a, ssc-miR-128, etc.) associated with PRRSV infection and immunity were screened as potential functional molecules involved in the regulation of PRRSV virus infection by exosomes.

Porcine reproductive and respiratory syndrome virus (PRRSV) has a highly restricted cell tropism, which is closely related to the specific receptors associated with PRRSV infection. At least nine cellular molecules have been identified as putative receptors for PRRSV, including CD163, a cysteine-rich scavenger receptor. With the participation of the CD163 receptor and other cofactors, PRRSV invades cells via low pH-dependent clathrin-mediated endocytosis. In addition, PRRSV utilizes viral apoptotic mimicry to infect cells though macropinocytosis as an alternative pathway. In this review, we discuss recent advances in the studies on receptors and pathways that play an important role in PRRSV invasion, and simultaneously explore the use of specific antibodies, small molecules, and blockers targeting receptor-ligand interactions, as a potential strategy for controlling PRRSV infection. Novel antiviral strategies against PRRSV could be developed by identifying the interaction between receptors and ligands.

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRS virus (PRRSV), is a highly contagious disease that brings tremendous economic losses to the global swine industry. As an intracellular obligate pathogen, PRRSV infects specific host cells to complete its replication cycle. PRRSV attachment to and entry into host cells are the first steps to initiate the replication cycle and involve multiple host cellular factors. In this review, we recapitulated recent advances on host cellular factors involved in PRRSV attachment and entry, and reappraised their functions in these two stages, which will deepen the understanding of PRRSV infection and provide insights to develop promising antiviral strategies against the virus.

Hosts exploit various approaches to defend against porcine reproductive and respiratory syndrome virus (PRRSV) infection. microRNAs (miRNAs) have emerged as key negative post-transcriptional regulators of gene expression and have been reported to play important roles in regulating virus infection. Here, we identified that miR-150 was differentially expressed in virus permissive and non-permissive cells. Subsequently, we demonstrated that PRRSV induced the expression of miR-150 via activating the protein kinase C (PKC)/c-Jun amino-terminal kinases (JNK)/c-Jun pathway, and overexpression of miR-150 suppressed PRRSV replication. Further analysis revealed that miR-150 not only directly targeted the PRRSV genome, but also facilitated type I IFN signaling. RNA immunoprecipitation assay demonstrated that miR-150 targeted the suppressor of cytokine signaling 1 (SOCS1), which is a negative regulator of Janus activated kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway. The inverse correlation between miR-150 and SOCS1 expression implies that miR-150 plays a role in regulating ISG expression. In conclusion, miR-150 expression is upregulated upon PRRSV infection. miR-150 feedback positively targets the PRRSV genome and promotes type I IFN signaling, which can be seen as a host defensive strategy.

MicroRNAs (miRNAs) play an important role in the virus-host interaction. Our previous work has indicated that the expression level of miR-10a increased in porcine alveolar macrophages (PAMs) during porcine reproductive and respiratory syndrome virus (PRRSV) infection and further inhibited viral replication through downregulates the expression of host molecule signal-recognition particle 14 (SRP14) protein. However, the molecular mechanism of miR-10a increased after PRRSV infection remains unknown. In the present study, transcription factor interferon regulatory factor 8 (IRF8) was identified as a negative regulator of miR-10a. PRRSV infection decreases the expression level of IRF8 in PAMs, leading to upregulating miR-10a expression to play an anti-PRRSV role. Meanwhile, this work first proved that IRF8 promoted PRRSV replication in an miR-10a-dependent manner. Further, we explained that SRP14, the target gene of miR-10a, promotes the synthesis of the PRRSV genome by interacting with the viral components Nsp2, thus facilitating PRRSV replication. In conclusion, we identified a novel IRF8-miR-10a-SRP14 regulatory pathway against PRRSV infection, which provides new insights into virus-host interactions and suggests potential new antiviral strategies to control PRRSV. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) has rapidly spread to the global pig industry and caused incalculable economic damage since first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection. Understanding the molecular mechanisms of host resistance to PRRSV infection is necessary to develop safe and effective strategies to control PRRSV. During viral infection, miRNAs play vital roles in regulating the expression of viral or host genes at the posttranscriptional level. The significance of our study is that we revealed the transcriptional regulation mechanism of the antiviral molecule miR-10a after PRRSV infection. Moreover, our research also explained the mechanism of host molecule SRP14, the target gene of miR-10a regulating PRRSV replication. Thus, we report a novel regulatory pathway of IRF8-miR-10a-SRP14 against PRRSV infection, which provides new insights into virus-host interactions and suggests potential new control measures for future PRRSV outbreaks.