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• Gal-1 overexpression strongly inhibits PRRSV replication in multiple strains. • Gal-1 knockdown or knockout facilitates PRRSV replication. • Interaction between Gal-1 and Nsp11 might regulate IFN and ISG activation. • Gal-1 exhibits antiviral activity against EAV, PEDV, JEV, PRV, and CSFV. • Gal-1 is potentially efficacious for applications to control PRRSV infection. Porcine reproductive and respiratory syndrome virus (PRRSV) causes great economic losses to the swine industry globally; however, effective control measures for this virus are limited. Here, we screened a porcine alveolar macrophage (PAM) cDNA library with a yeast two-hybrid system to reveal that galectin-1 (Gal-1), an endogenous innate immune protein encoded by LGALS1 , interacts with nonstructural protein 11 (Nsp11) of PRRSV. Western blotting and viral titer assays indicated that Gal-1 overexpression suppressed replication in multiple PRRSV strains (P < 0.001), whereas Gal-1 knockdown or knockout increased viral titer and nucleocapsid protein expression. The Gal-1-specific anti-PRRSV effect was associated with the endoribonuclease domain of Nsp11 through inactivation of interferon-antagonist function and stimulation of interferon-stimulated gene expression. Additionally, Gal-1 interacted with PRRSV E protein but not with PRRSV glycoproteins, and recombinant Gal-1 treatment inhibited PRRSV in PAMs and MARC-145 cells. Furthermore, Gal-1 inhibited replication in multiple viruses, including equine arteritis virus, porcine epidemic diarrhea virus, pseudorabies virus, Japanese encephalitis virus, and classical swine fever virus, suggesting its potential broad application for antiviral strategies. Our findings provide insight into the important role of Gal-1 in PRRSV pathogenesis and its potential use as a novel therapeutic target against PRRSV infection. [ABSTRACT FROM AUTHOR]

KLF16, a member of KLFs (Krüppel-like factors), contributes to the progression of a variety of cancer types. There is, however, still uncertain regarding the role of KLF16 in viral replication and the signaling mechanism of type I IFN. It was discovered that KLF16 inhibited the replication of porcine epidemic diarrhea virus (PEDV) through the type I IFN signaling pathway. Besides, it can also be found that the expression of KLF16 was down-regulated after PEDV infection of LLC-PK1 cells. Furthermore, overexpression of KLF16 inhibited the replication of PEDV in Vero cells as well as LLC-PK1 cells, whereas the replication of PEDV was promoted by the knockdown of KLF16. KLF16 up-regulated the expression of interferons (IFNs) via the TRAF6-pTBK1-pIRF3 pathway with the aim of promoting the host antiviral innate immune response. In addition, the obtained findings proved that KLF16 plays a novel role in antiviral action, thereby offering novel possibilities for preventing and controlling PEDV. • KLF16 was downregulated in porcine epidemic diarrhea virus (PEDV)-infected LLC-PK1 cells. • KLF16 overexpression inhibited PEDV proliferation in both Vero cells and LLC-PK1 cells. • KLF16 silencing promoted PEDV replication. • KLF16 inhibited PEDV replication by activating type-I IFN signaling via the TRAF6-pTBK1-pIRF3 pathway. [ABSTRACT FROM AUTHOR]

Autophagy-related 4B (ATG4B) is found to exert a vital function in viral replication, although the mechanism through which ATG4B activates type-I IFN signaling to hinder viral replication remains to be explained, so far. The current work revealed that ATG4B was downregulated in porcine epidemic diarrhea virus (PEDV)-infected LLC-PK1 cells. In addition, ATG4B overexpression inhibited PEDV replication in both Vero cells and LLC-PK1 cells. On the contrary, ATG4B knockdown facilitated PEDV replication. Moreover, ATG4B was observed to hinder PEDV replication by activating type-I IFN signaling. Further detailed analysis revealed that the ATG4B protein targeted and upregulated the TRAF3 protein to induce IFN expression via the TRAF3-pTBK1-pIRF3 pathway. The above data revealed a novel mechanism underlying the ATG4B-mediated viral restriction, thereby providing novel possibilities for preventing and controlling PEDV. • ATG4B was downregulated in porcine epidemic diarrhea virus (PEDV)-infected LLC-PK1 cells. • ATG4B overexpression inhibited PEDV proliferation in both Vero cells and LLC-PK1 cells. • ATG4B knockdown promoted PEDV replication. • ATG4B hindered PEDV replication by activating type-I IFN signaling via the TRAF3-pTBK1-pIRF3 pathway. [ABSTRACT FROM AUTHOR]

• rPRRSV-E2 is a marker vaccine for CSFV. • rPRRSV-E2 is promising as a virus-vectored vaccine against both HP-PRRSV and CSFV infection in swine herds by single vaccination. • Maternal derived antibodies (MDAs) do not interfere with the immune efficacy of rPRRSV-E2. Currently live attenuated porcine reproductive and respiratory syndrome (PRRS) and classical swine fever (CSF) vaccines are widely used in Chinese swine herds. However, the mutual effects of vaccination procedures and severe stress caused by successive vaccinations harm piglets and make it difficult to stimulate robust and effective immune responses. In our previous study, a recombinant PRRS virus (PRRSV) vectored vaccine candidate rPRRSV-E2, which expresses CSF virus (CSFV) E2 protein, has been demonstrated being able to protect piglets against lethal challenge of highly-pathogenic (HP)-PRRSV and CSFV. In this study, we determine whether preexisting maternally derived antibodies (MDA) interfere with the immune efficacy of rPRRSV-E2. 8 experimental groups of piglets, with or without PRRSV MDAs or CSFV MDAs were immunized with a single dose of 105 TCID 50 rPRRSV-E2 or DMEM and challenged with HP-PRRSV or CSFV. Clinical characteristics, PRRSV- or CSFV-specific antibodies, viremia and pathological changes were monitored, examined and analyzed. The results showed that rPRRSV-E2-vaccinated piglets, either with or without MDAs directed against PRRSV or CSFV were completely protected from the lethal challenge of HP-PRRSV or CSFV. These results demonstrate that the MDAs do not interfere with the immune efficacy of rPRRSV-E2, which indicates that rPRRSV-E2 could have great significance in the effective prevention and control of HP-PRRSV and CSFV. [ABSTRACT FROM AUTHOR]

• RNF114 exhibits significant anti-PRRSV activity. • RNF114 knockdown facilitates PRRSV replication. • PRRSV infection leads to endogenous RNF114 upregulation. • The E3 ligase RNF114 interacts with Nsp12 and promotes its proteasomal degradation. • RNF114 catalyzes K27-linked polyubiquitination of PRRSV Nsp12. Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to the swine industry worldwide, and the development of effective and sustainable measures to control PRRSV transmission remains a pressing problem. The function of PRRSV nonstructural protein 12 (Nsp12), which might play essential roles in viral replication and production, remains unknown. In this study, we identified a new host-restricted factor, porcine RING finger protein 114 (RNF114), as an inhibitor of PRRSV replication through its degradation of viral Nsp12. Western blot, quantitative real-time polymerase chain reaction, and viral titer assays indicated that RNF114 overexpression suppressed PRRSV replication, whereas RNF114 knockdown increased viral titer and nucleocapsid protein levels. Additionally, we observed that PPRSV infection led to increased RNF114 levels during the middle and late phases of infection in both porcine alveolar macrophages and MARC-145 cells. Moreover, screening of PRRSV Nsps showed that RNF114 interacted with viral Nsp12, and that RNF114-specific anti-PRRSV effects were associated with its ubiquitin ligase activity, which involves K27-linked polyubiquitination and degradation of Nsp12 through a proteasome-dependent pathway. These findings identified RNF114 as a critical regulator of PRRSV replication and offer insights into the roles of Nsp12 in PRRSV pathogenesis. [ABSTRACT FROM AUTHOR]