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Abstract Pseudorabies virus (PRV) is recognized as the aetiological agent responsible for Aujeszky’s disease, or pseudorabies, in swine populations. Rab6, a member of the small GTPase family, is implicated in various membrane trafficking processes, particularly exocytosis regulation. Its involvement in PRV infection, however, has not been documented previously. In our study, we observed a significant increase in the Rab6 mRNA and protein levels in both PK-15 porcine kidney epithelial cells and porcine alveolar macrophages, as well as in the lungs and spleens of mice infected with PRV. The overexpression of wild-type Rab6 and its GTP-bound mutant facilitated PRV proliferation, whereas the GDP-bound mutant form of Rab6 had no effect on viral propagation. These findings indicated that the GTPase activity of Rab6 was crucial for the successful spread of PRV. Further investigations revealed that the reduction in Rab6 levels through knockdown significantly hampered PRV proliferation and disrupted virus assembly and egress. At the molecular level, Rab6 was found to interact with the PRV glycoproteins gB and gE, both of which are essential for viral assembly and egress. Our results collectively suggest that PRV exploits Rab6 to expedite its assembly and egress and identify Rab6 as a promising novel target for therapeutic treatment for PRV infection.

RAB GTPases (RABs) control intracellular membrane trafficking with high precision. In the present study, we carried out a short hairpin RNA (shRNA) screen focused on a library of 62 RABs during infection with porcine reproductive and respiratory syndrome virus 2 (PRRSV-2), a member of the family Arteriviridae. We found that 13 RABs negatively affect the yield of PRRSV-2 progeny virus, whereas 29 RABs have a positive impact on the yield of PRRSV-2 progeny virus. Further analysis revealed that PRRSV-2 infection transcriptionally regulated RAB18 through RIG-I/MAVS-mediated canonical NF-κB activation. Disrupting RAB18 expression led to the accumulation of lipid droplets (LDs), impaired LDs catabolism, and flawed viral replication and assembly. We also discovered that PRRSV-2 co-opts chaperone-mediated autophagy (CMA) for lipolysis via RAB18, as indicated by the enhanced associations between RAB18 and perlipin 2 (PLIN2), CMA-specific lysosomal associated membrane protein 2A (LAMP2A), and heat shock protein family A (Hsp70) member 8 (HSPA8/HSC70) during PRRSV-2 infection. Knockdown of HSPA8 and LAMP2A impacted on the yield of PRRSV-2 progeny virus, implying that the virus utilizes RAB18 to promote CMA-mediated lipolysis. Importantly, we determined that the C-terminal domain (CTD) of HSPA8 could bind to the switch II domain of RAB18, and the CTD of PLIN2 was capable of associating with HSPA8, suggesting that HSPA8 facilitates the interaction between RAB18 and PLIN2 in the CMA process. In summary, our findings elucidate how PRRSV-2 hijacks CMA-mediated lipid metabolism through innate immune activation to enhance the yield of progeny virus, offering novel insights for the development of anti-PRRSV-2 treatments.

Abstract The porcine pseudorabies virus (PRV) is one of the most devastating pathogens and brings great economic losses to the swine industry worldwide. Viruses are intracellular parasites that have evolved numerous strategies to subvert and utilize different host processes for their life cycle. Among the different systems of the host cell, the cytoskeleton is one of the most important which not only facilitate viral invasion and spread into neighboring cells, but also help viruses to evade the host immune system. RhoA is a key regulator of cytoskeleton system that may participate in virus infection. In this study, we characterized the function of RhoA in the PRV replication by chemical drugs treatment, gene knockdown and gene over-expression strategy. Inhibition of RhoA by specific inhibitor and gene knockdown promoted PRV proliferation. On the contrary, overexpression of RhoA or activation of RhoA by chemical drug inhibited PRV infection. Besides, our data demonstrated that PRV infection induced the disruption of actin stress fiber, which was consistent with previous report. In turn, the actin specific inhibitor cytochalasin D markedly disrupted the normal fibrous structure of intracellular actin cytoskeleton and decreased the PRV replication, suggesting that actin cytoskeleton polymerization contributed to PRV replication in vitro. In summary, our data displayed that RhoA was a host restriction factor that inhibited PRV replication, which may deepen our understanding the pathogenesis of PRV and provide further insight into the prevention of PRV infection and the development of anti-viral drugs.

Viral infection is a significant risk factor for fertility issues. Here, we demonstrated that infection by neurotropic alphaherpesviruses, such as pseudorabies virus (PRV), could impair female fertility by disrupting the hypothalamus-pituitary-ovary axis (HPOA), reducing progesterone (P4) levels, and consequently lowering pregnancy rates. Our study revealed that PRV exploited the transient receptor potential mucolipin 1 (TRPML1) and its lipid activator, phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), to facilitate viral entry through lysosomal cholesterol and Ca2+. P4 antagonized this process by inducing lysosomal storage disorders and promoting the proteasomal degradation of TRPML1 via murine double minute 2 (MDM2)-mediated polyubiquitination. Overall, the study identifies a novel mechanism by which PRV hijacks the lysosomal pathway to evade P4-mediated antiviral defense and impair female fertility. This mechanism may be common among alphaherpesviruses and could contribute significantly to their impact on female reproductive health, providing new insights for the development of antiviral therapies.

ABSTRACTViruses have evolved sophisticated mechanisms to manipulate host cell organelles to serve as niches for persistence and proliferation. In the present study, we aimed to investigate the role of cellular organelles in the replication of porcine reproductive and respiratory syndrome virus (PRRSV). We found that the morphology of mitochondria and the endoplasmic reticulum (ER) were both altered, and the contact between these two organelles was enhanced during PRRSV infection. By the overexpression of PRRSV-encoded open reading frames, we identified that only glycoprotein 5 (GP5) was essential for ER-mitochondria contact. Further investigation revealed that GP5 interacted with the ER inositol 1,4,5-triphosphate receptor (IP3R) and the mitochondrial voltage-dependent anion channel (VDAC1) to promote the Ca2+ efflux from ER into mitochondria. Excessive mitochondrial Ca2+ uptake resulted in mitochondrial dysfunction and substantial mitochondrial reactive oxygen species (mROS) production. Elevated mROS activated autophagy through the AMPK/mROR/ULK1 axis to facilitate PRRSV replication. GP5-induced mROS also triggered the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Inhibition of autophagy augmented NLRP3 inflammasome activation and exhibited an anti-PRRSV effect, suggesting autophagy counteracted the NLRP3-mediated innate immune response. Overall, our findings highlighted the importance of cellular organelles in virus-host interactions and provided new insights into the complex interplay between virus replication and innate immune responses.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) presents a significant economic concern for the global swine industry due to its connection to serious production losses and increased mortality rates. There is currently no specific treatment for PRRSV. Previously, we had uncovered that PRRSV-activated lipophagy to facilitate viral replication. However, the precise mechanism that PRRSV used to trigger autophagy remained unclear. Here, we found that PRRSV GP5 enhanced mitochondrial Ca2+ uptake from ER by promoting ER-mitochondria contact, resulting in mROS release. Elevated mROS induced autophagy, which alleviated NLRP3 inflammasome activation for optimal viral replication. Our study shed light on a novel mechanism revealing how PRRSV exploits mROS to facilitate viral replication.

In this study, a new {Co9} cluster-added polyoxometalate (POM) Cs3K4Na5H6[BO(OH)2Co9O(OH)(H2O)3(GeW6O26)(B-α-GeW9O34)2]·22H2O (1) was successfully synthesized in the presence of inorganic boron sources under hydrothermal conditions. Its structural characterizaiton is realized using single-crystal X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, and powder X-ray diffraction. Compound 1 represents the first Co-added POM bonded by a B atom, and its polyoxoanion is constructed by fusing together with one hexalacunary GeW6O26 and two trilacunary B-α-GeW9O34 fragments in an unprecedented V-shaped {Co9} cluster. Additionally, compound 1 is an efficient catalyst for accelerating the Knoevenagel condensation of various aldehydes with malonitrile.

An acentric hexa-Ti-oxo-cluster-added trimeric phosphotungstate, [H2N(CH3)2]3H12[Ti6O6(A-α-1,2-PW10O37)3]∙12 H2O (1), was synthesized by reacting trivacant polyoxometalate (POM) fragments with Ti4+ ions under hydrothermal conditions and characterized via single-crystal/powder X-ray diffraction, solid UV–vis and IR spectroscopies, and thermogravimetric analysis. The polyoxoanion of 1 is constituted by three Ti2O3(A-α-1,2-PW10O37) subunits linked through Ti–O–Ti bonds, forming a ring-shaped configuration. Furthermore, 1 exhibits a second-harmonic generation response about 0.6 times that of KH2PO4, which paves the way toward the development of Ti-added POMs in the field of nonlinear optical materials.

Two new aluminoborates, NaKCs[AlB7O13(OH)]·H2O (1) and K4Na5[AlB7O13(OH)]3·5H2O (2), have been hydro(solvo)thermally made with mixed alkali metal cationic templates. Both 1 and 2 crystallize in the monoclinic space group P21/n and contain similar units of [B7O13(OH)]6− cluster and AlO4 tetrahedra. The [B7O13(OH)]6− cluster is composed of three classical B3O3 rings by vertex sharing, of which two of them connect with AlO4 tetrahedra to constitute monolayers, and one provides an O atom as a bridging unit to link two oppositely orientated monolayers by Al-O bonds to form 3D porous-layered frameworks with 8-MR channels. UV-Vis diffuse reflectance spectra indicate that both 1 and 2 exhibit short deep-UV cutoff edges below 190 nm, revealing that they have potential applications in deep-UV regions.

Abstract Pseudorabies, caused by pseudorabies virus (PRV) variants, has broken out among commercial PRV vaccine-immunized swine herds and resulted in major economic losses to the pig industry in China since late 2011. However, the mechanism of virulence enhancement of variant PRV is currently unclear. Here, a recombinant PRV (rPRV HN1201-EGFP-Luc) with stable expression of enhanced green fluorescent protein (EGFP) and firefly luciferase as a double reporter virus was constructed on the basis of the PRV variant HN1201 through CRISPR/Cas9 gene-editing technology coupled with two sgRNAs. The biological characteristics of the recombinant virus and its lethality to mice were similar to those of the parental strain and displayed a stable viral titre and luciferase activity through 20 passages. Moreover, bioluminescence signals were detected in mice at 12 h after rPRV HN1201-EGFP-Luc infection. Using the double reporter PRV, we also found that 25-hydroxycholesterol had a significant inhibitory effect on PRV both in vivo and in vitro. These results suggested that the double reporter PRV based on PRV variant HN1201 should be an excellent tool for basic virology studies and evaluating antiviral agents.

ABSTRACT Porcine reproductive and respiratory syndrome virus (PRRSV) infection leads to late-term reproductive failure and respiratory illness that affect the global swine industry. Epigallocatechin gallate (EGCG) is a polyphenolic compound from green tea that exerts antiviral activity against diverse viruses. This study aimed to report an uncharacterized mechanism of how EGCG restricted PRRSV proliferation. EGCG showed no significant effects on cell viability, cell cycle progression, and apoptosis in porcine alveolar macrophages and MARC-145 cells. The treatment of cells with EGCG attenuated the replication of both highly pathogenic and less pathogenic PRRSV in vitro. The viral life cycle analysis demonstrated that EGCG affected PRRSV replication and assembly, but not viral attachment, entry, or release. Interestingly, EGCG treatment abrogated the increased lipid droplets formation and lipid content induced by PRRSV infection. We further demonstrated that EGCG blocked PRRSV-stimulated expression of the key enzymes in lipid synthesis. In addition, EGCG attenuated PRRSV-induced autophagy that is critical for PRRSV proliferation. The supplementation of oleic acid restored PRRSV replication and assembly under EGCG treatment. Together, our results support that EGCG inhibits PRRSV proliferation through disturbing lipid metabolism. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped single-positive-stranded RNA virus that causes acute respiratory distress in piglets and reproductive failure in sows, resulting in huge economic losses to the global swine industry. Several lines of evidence have suggested the crucial roles of lipids in PRRSV proliferation. Our previous report demonstrated that PRRSV activated lipophagy to facilitate viral replication through downregulating the expression of N-Myc downstream-regulated gene 1. The manipulation of lipid metabolism may be a new perspective to prevent PRRSV spread. In the present study, we reported that epigallocatechin-3-gallate (EGCG), the major component of green tea catechins, significantly attenuated PRRSV infection through inhibiting lipid synthesis and autophagy. Given that natural products derived from plants have helped in the prevention and treatment of various infectious diseases, EGCG has a great potential to serve as a safe and environmentally friendly natural compound to treat PRRSV infection.

A polyanion cluster H6Na8Cs3[Co9(μ3-OH)3(H2O)6(HPO4)2(B-α-PW9O34)3]Cl·40H2O (1) was made with the guidance of the lacunary directing strategy under hydrothermal conditions. Compound 1 was characterized by single-crystal X-ray diffraction, powder X-ray diffraction, and thermogravimetric analysis, respectively. Single-crystal X-ray diffraction analyses showed that 1 consists of three anions [B-α-PW9O34]9− and a cyclic cationic [Co9(μ3-OH)3(H2O)6]15+ and two anions HPO42−. Variable-magnetic properties indicate antiferromagnetic interactions in 1. Visible-light-driven hydrogen evolution tests demonstrated that 1 was an efficient water reduction catalyst with an H2 evolution rate of 1217.6 μmol h−1 g−1.

Two new nonaborates, Na2Ba0.5[B9O15]·H2O (1) and Na4Ca1.5[B9O16(OH)2] (2), have been solvothermally made with mixed alkali and alkaline-earth metal cationic templates. 1 and 2 are constructed by two different types of nonaborate clusters. In 1, the [B9O19]11− cluster is composed of three corner-sharing [B3O7]5− clusters, of which two of them interconnect to the 1D B3O7-based chains and are further bridged to the 3D framework with 7 types of 10-MR channels by another [B3O7]5− bridging cluster. The [B9O18(OH)2]11− cluster in 2 is made of four BO4-sharing [B3O8]7− clusters. As a 4-connected node, the interconnections of [B9O18(OH)2]11− construct the unpreceded 2D layer with large 14-MR windows, which are further joined by H-bonds to the 3D supramolecular framework. UV–Vis absorption spectra reveal that both 1 and 2 have short cutoff edges below 190 nm, exhibiting bandgaps of 6.31 and 6.39 eV, respectively, indicating their potential applications in deep UV (DUV) regions.

Three new hexa-Ni-substituted Keggin-type polyoxometalates (POMs), [Ni6(OH)3- (DACH)3(H2O)6(PW9O34)]·31H2O (1), [Ni(DACH)2][Ni6(OH)3(DACH)3(HMIP)2(H2O)2(PW9O34)]·56 H2O (2), and [Ni(DACH)2][Ni6(OH)3(DACH)2(AP)(H2O)5(PW9O34)]·2H2O (3) (DACH = 1,2-Diami- nocyclohexane, MIP = 5-Methylisophthalate, AP = Adipate) were successfully made in the presence of DACH under hydrothermal conditions. 1 is an isolated hexa-Ni-substituted Keggin unit decorated by DACH. In order to further construct POM cluster-organic frameworks (POMCOFs) on the basis of 1, by analyzing the steric hindrances and orientations of the POM units, the rigid HMIP and flexible AP ligands were successively incorporated, and another anionic monomeric POM 2 and the new 1D POM cluster organic chain (POMCOC) 3 were obtained. HMIP ligand still acts as a decorating group on the Ni6 core of 2 but results in the different spatial arrangement of the {Ni6PW9} units. AP ligands in 3 successfully bridge adjacent isolated POM cluster units to 1D POMCOC with left-hand helices. The AP in 3 is the longest aliphatic carboxylic acid ligand in POMs, and the 1D POM cluster-AP helical chain represents the first 1D POMCOC with a helical feature.

Myostatin (Mstn) is postulated to be a key determinant of muscle loss and cachexia in cancer. However, no experimental evidence supports a role for Mstn in cancer, particularly in regulating the survival and growth of cancer cells. In this study, we showed that the expression of Mstn was significantly increased in different tumor tissues and human cancer cells. Mstn knockdown inhibited the proliferation of cancer cells. A knockout (KO) of Mstn created by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 9 (CRISPR/Cas9) induced mitochondria-dependent apoptosis in HeLa cells. Furthermore, KO of Mstn reduced the lipid content. Molecular analyses demonstrated that the expression levels of fatty acid oxidation-related genes were upregulated and then increased rate of fatty acid oxidation. Mstn deficiency-induced apoptosis took place along with generation of reactive oxygen species (ROS) and elevated fatty acid oxidation, which may play a role in triggering mitochondrial membrane depolarization, the release of cytochrome c (Cyt-c), and caspase activation. Importantly, apoptosis induced by Mstn KO was partially rescued by antioxidants and etomoxir, thereby suggesting that the increased level of ROS was functionally involved in mediating apoptosis. Overall, our findings demonstrate a novel function of Mstn in regulating mitochondrial metabolism and apoptosis within cancer cells. Hence, inhibiting the production and function of Mstn may be an effective therapeutic intervention during cancer progression and muscle loss in cachexia. Keywords: Myostatin, CRISPR/Cas9, Apoptosis, Reactive oxygen species

Pseudorabies virus (PRV) is a contagious herpesvirus that causes Aujeszky’s disease and economic losses worldwide. Liver X receptors (LXRs) belong to the nuclear receptor superfamily and are critical for the control of lipid homeostasis. However, the role of LXR in PRV infection has not been fully established. In this study, we found that PRV infection downregulated the mRNA and protein levels of LXRα and LXRβ in vitro and in vivo. Furthermore, we discovered that LXR activation suppressed PRV proliferation, while LXR inhibition promoted PRV proliferation. We demonstrated that LXR activation-mediated reduction of cellular cholesterol was critical for the dynamics of PRV entry-dependent clathrin-coated pits. Replenishment of cholesterol restored the dynamics of clathrin-coated pits and PRV entry under LXR activation conditions. Interestingly, T0901317, an LXR agonist, prevented PRV infection in mice. Our results support a model that PRV modulates LXR-regulated cholesterol metabolism to facilitate viral proliferation.

Pigs have anatomical and physiological characteristics comparable to those in humans and, therefore, are a favorable model for immune function research. Interferons (IFNs) and inflammasomes have essential roles in the innate immune system. Here, we report that G10, a human-specific agonist of stimulator of interferon genes (STING), activates both type I IFN and the canonical NLRP3 inflammasome in a STING-dependent manner in porcine cells. Without a priming signal, G10 alone transcriptionally stimulated Sp1-dependent p65 expression, thus triggering activation of the nuclear factor-κB (NF-κB) signaling pathway and thereby priming inflammasome activation. G10 was also found to induce potassium efflux- and NLRP3/ASC/Caspase-1-dependent secretion of IL-1β and IL-18. Pharmacological and genetic inhibition of NLRP3 inflammasomes increased G10-induced type I IFN expression, thereby preventing virus infection, suggesting negative regulation of the NLRP3 inflammasome in the IFN response in the context of STING-mediated innate immune activation. Overall, our findings reveal a new mechanism through which G10 activates the NLRP3 inflammasome in porcine cells and provide new insights into STING-mediated innate immunity in pigs compared with humans.

Emerging viral pathogens cause substantial morbidity and pose a severe threat to health worldwide. However, a universal antiviral strategy for producing safe and immunogenic inactivated vaccines is lacking. Here, we report an antiviral strategy using the novel singlet oxygen (1O2)-generating agent LJ002 to inactivate enveloped viruses and provide effective protection against viral infection. Our results demonstrated that LJ002 efficiently generated 1O2 in solution and living cells. Nevertheless, LJ002 exhibited no signs of acute toxicity in vitro or in vivo. The 1O2 produced by LJ002 oxidized lipids in the viral envelope and consequently destroyed the viral membrane structure, thus inhibiting the viral and cell membrane fusion necessary for infection. Moreover, the 1O2-based inactivated pseudorabies virus (PRV) vaccine had no effect on the content of the viral surface proteins. Immunization of mice with LJ002-inactiviated PRV vaccine harboring comparable antigen induced more neutralizing antibody responses and efficient protection against PRV infection than conventional formalin-inactivated vaccine. Additionally, LJ002 inactivated a broad spectrum of enveloped viruses. Together, our results may provide a new paradigm of using broad-spectrum, highly effective inactivants functioning through 1O2-mediated lipid oxidation for developing antivirals that target the viral membrane fusion process.

Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases.

A new series of coumarin derivatives, 7-hydroxy-7-(trifluoromethyl)-6a,12b-dihydro-6H,7H-chromeno[3,4-c]chromen-6-ones 3a−p, were synthesized via Michael addition, transesterification and nucleophilic addition from the reaction of 3-trifluoroacetyl coumarins and phenols in the presence of an organic base. The products were characterized by infrared spectroscopy (IR), hydrogen nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR) and high-resolution mass spectrometer (HRMS). Single crystal X-ray analysis of compounds 3a and 3n clearly confirmed their assigned chemical structures and their twisted conformations. Compound 3a crystallized in the orthorhombic system, Pbca, in which a = 8.6244(2) Å, b = 17.4245(4) Å, c = 22.5188(6) Å, α = 90°, β = 90°, γ = 90°, v = 3384.02(14) Å3, and z = 8. In addition, the mycelial growth rate method was used to examine the in vitro antifungal activities of the title compounds 3a−p against Fusarium graminearum and Fusarium monitiforme at 500 µg/mL. The results showed that compound 3l exhibited significant anti-Fusarium monitiforme activity with inhibitory index of 84.6%.

The title compound, C19H14O4, was prepared by the reaction of 2-oxo-2H-chromene-3-acyl chloride with cinnamic alcohol. The whole molecule is not planar, the dihedral angle between the planes of coumarin and benzene rings being 13.94 (4)°, but the plane of the coumarin ring and that of the ester group are almost coplanar, making a dihedral angle of 2.9 (1)°. In the crystal structure, weak intermolecular C—H...O hydrogen bonds link two molecules into dimers, and π–π stacking interactions between inversion-related rings of the coumarin groups [centroid–centroid distance 3.8380 (15) Å with a slippage of 1.535 Å], which connect the dimers into columns extending along [010].

The title compound, C20H24O4, was synthesized from the reaction of 2-oxo-2H-chromene-3-acyl chloride and menthol. The mean plane of the ester group and that of the four essentially planar (maximum deviation 0.0112 Å) C atoms of the chair-form cyclohexyl ring form dihedral angles of 43.8 (3) ° and 81.8 (1)°, respectively, with the mean plane of the coumarin ring system. In the crystal structure, weak intermolecular C—H...O hydrogen bonds connect the molecules into a two-dimensional network.

The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky's disease, which results in considerable economic impacts globally. The enzyme tryptophanyl-tRNA synthetase 2 (WARS2), a mitochondrial protein involved in protein synthesis, is recognized for its broad expression and vital role in the translation process. The findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV infection in both cell cultures and animal models. Suppressing WARS2 expression via RNA interference in PK-15 cells led to a reduction in PRV infection rates, whereas enhancing WARS2 expression resulted in increased infection rates. Furthermore, the activation of WARS2 in response to PRV was found to be reliant on the cGAS/STING/TBK1/IRF3 signaling pathway and the interferon-alpha receptor-1, highlighting its regulation via the type I interferon signaling pathway. Further analysis revealed that reducing WARS2 levels hindered PRV's ability to promote protein and lipid synthesis. Our research provides novel evidence that WARS2 facilitates PRV infection through its management of protein and lipid levels, presenting new avenues for developing preventative and therapeutic measures against PRV infections. [ABSTRACT FROM AUTHOR]