Porcine circoviruses (PCVs) are members of the genus Circovirus of the family Circoviridae, and four species of PCVs have been discovered and named PCV1–PCV4, respectively. With the first report of PCV3 in America in 2016, the pathogenic variant was found to be associated with various clinical features, called porcine circovirus associated disease (PCVAD), including multisystemic inflammation, porcine dermatitis and nephropathy syndrome (PDNS), reproductive disorders, respiratory or digestive disorders. Increasing experimental data have shown that PCV3 is widespread around the world, but the failure of virus isolation and propagation has put obstacles in the way of PCV3 research. Moreover, a large number of reports demonstrate that PCV3 usually co-infects with other pathogens in pigs. Thus, whether PCV3 alone causes clinical manifestations needs to be fully discussed. In addition, the host cell immune response was activated during PCV3 infection, and PCV3-encoded proteins may regulate immune responses to facilitate its replication. An in-depth understanding of PCV3 pathogenesis and immune regulation strategies is critical for PCVAD prevention. In this review, the advances in pathogenicity and innate immune modulation of PCV3 were summarized, which could deepen the understanding of this virus and PCV3-related diseases.

Japanese encephalitis virus (JEV) is the causative agent of Japanese encephalitis, which poses great threats to the pig farming industry and human health. To establish infection, JEV has evolved sophisticated strategies to overcome the innate immune responses and finish its life cycle. Previous studies have shown that non-structural protein 1 (NS1) is closely related to its pathogenesis, while its molecular mechanism remains elusive. In this study, host protein ATP-dependent RNA helicase DEAD-box helicase 3 X (DDX3X) was screened to bind with NS1, and both ectopically expressed and virally encoded NS1 further confirmed their interaction. We also proved that the β-roll and wing subdomains of NS1 were responsible for their interaction. In DDX3X-overexpressing cells, the replication of JEV was markedly inhibited, while the viral titers were elevated in DDX3X-silencing cells, indicating that DDX3X might serve as an anti-viral factor during JEV infection. Mechanically, overexpression of DDX3X promotes interferon-beta (IFN-β) transcription, while its transcription was decreased in DDX3X-silencing cells. Consistent with IFN-β, some interferon-stimulated genes (ISGs), including protein kinase R (PKR), myxovirus resistance 1 (MX1), guanylate-binding protein 1 (GBP1), and bone marrow stromal antigen 2 (BST2), were also positively related to the DDX3X expression. Taken together, JEV NS1 blocks IFN-β production by interacting with DDX3X to evade the host’s innate immune response and facilitate virus replication. This finding will deepen our understanding of JEV immune-evasion strategies and provide targets for JEV attenuation. IMPORTANCE: This study focused on JEV, a threat to pig farming and human health. The key finding is that NS1 binds to host protein DDX3X via its β-roll and wing subdomains. JEV NS1 evades the host immune response by interacting with DDX3X to restrain type I interferon production. These results deepen our understanding of JEV’s immune-evasion strategies and offer potential targets for JEV attenuation.

Suid herpesvirus 1 (SuHV-1), known as pseudorabies virus (PRV), is one of the most devastating swine pathogens in China, particularly the sudden occurrence of PRV variants in 2011. The higher pathogenicity and cross-species transmission potential of the newly emerged variants caused not only colossal economic losses, but also threatened public health. To uncover the underlying pathogenesis of PRV variants, Tandem Mass Tag (TMT)-based proteomic analysis was performed to quantitatively screen the differentially expressed cellular proteins in PRV-infected Vero cells. A total of 7072 proteins were identified and 960 proteins were significantly regulated: specifically 89 upregulated and 871 downregulated. To make it more credible, the expression of XRCC5 and XRCC6 was verified by western blot and RT-qPCR, and the results dovetailed with the proteomic data. The differentially expressed proteins were involved in various biological processes and signaling pathways, such as chaperonin-containing T-complex, NIK/NF-κB signaling pathway, DNA damage response, and negative regulation of G2/M transition of mitotic cell cycle. Taken together, our data holistically outline the interactions between PRV and host cells, and our results may shed light on the pathogenesis of PRV variants and provide clues for pseudorabies prevention.

Japanese encephalitis (JE) is a natural zoonotic disease caused by the Japanese encephalitis virus (JEV), which poses potential threats to human health and the pig farming industry. To establish infection, JEV must overcome the innate immune responses and complete its lifecycle in new hosts. Notably, the direct virus-induced neuronal cell death and an uncontrolled neuroinflammatory response jointly lead to the pathogenesis of JEV. In this review, we will focus on the innate immune response to JEV infection and the viral immune evasion strategies, such as escaping recognition or inhibiting the production of antiviral factors. Generally, JEV exploits four innate immune pathways, including type I interferon, interleukins, programmed cell death, and autophagy, to facilitate self-replication or exacerbate disease. Moreover, host microRNAs modulated during JEV infection have emerged as key regulators of this virus–host interplay. Therefore, a full understanding of how the immune system reacts to JEV infection and how the virus evades innate immune clearance will help develop effective vaccines or antiviral therapies.

Japanese encephalitis virus causes a huge threat to the pig-raising industry and attenuated-live vaccines are widely used to prevent JEV infection. Nowadays, primary hamster kidney cells and Vero cells are mostly used for the propagation of JEV attenuated vaccines. In this research, we constructed porcine-derived-immortalized mesangial cells (PMCs) for JEV cultivation, and their characteristics were also studied. The prepared PMCs were uniform in shape and without variation in chromosome numbers. Furthermore, PMCs showed strong division and proliferation ability, and JEV could replicate efficiently as well causing a cytopathic effect similar to that in Vero cells. The viral tiler results showed that JEV grows faster in PMCs compared with that in Vero cells. Taken together, we generated an immortalized PMC cell line competent for the cultivation of JEV, which has significance for the production of pig JEV attenuated vaccines.