Xiaoyu Tang

Pseudorabies virus (PRV) is considered to be a promising oncolytic virus that has potential as a cancer gene therapy drug. In this study, PRV-DCD-1-70 was used as a vector to carry exogenous genes IL-18, IFN-γ and PH20 to construct novel recombinant PRV, rPRV-PH20 and rPRV-IL-18-γ-PH20, and their tumorolytic effects were evaluated in vitro and in vivo. Our study showed that recombinant PRV lysed all four tumor cell lines, Pan02, EMT-6, CT26 and H446, and rPRV-IL-18-γ-PH20 showed the best tumor lysis effect. Further studies in mice bearing Pan02 tumors showed that recombinant PRV, especially rPRV-IL-18-γ-PH20, were able to inhibit tumor growth. Moreover, an immunohistochemical analysis indicated that the recombinant PRV effectively increased the infiltration of CD4⁺T and CD8⁺T cells and enhanced the anti-tumor immune response of the organism in vivo. Overall, PRV carrying PH20 and IL-18-γ exogenous genes demonstrated anti-tumor effects, providing a foundation for the further development and application of PRV as a novel tumor oncolytic virus vector.

Senecavirus A (SVA) is an oncolytic RNA virus, and it is the ideal oncolytic virus that can be genetically engineered for editing. However, there has not been much exploration into creating SVA viruses that carry antitumor genes to increase their oncolytic potential. The construction of SVA viruses carrying antitumor genes that enhance oncolytic potential has not been fully explored. In this study, a recombinant SVA-CH-01-2015 virus (p15A-SVA-clone) expressing the human p16^INK4A protein, also known as cell cycle-dependent protein kinase inhibitor 2A (CDKN2A), was successfully rescued and characterized. The recombinant virus, called SVA-p16, exhibited similar viral replication kinetics to the parent virus, was genetically stable, and demonstrated enhanced antitumor effects in Ishikawa cells. Additionally, another recombinant SVA virus carrying a reporter gene (iLOV), SVA-iLOV, was constructed and identified using the same construction method as an auxiliary validation. Collectively, this study successfully created a new recombinant virus, SVA-p16, that showed increased antitumor effects and could serve as a model for further exploring the antitumor potential of SVA as an oncolytic virus.

Seneca Valley virus (SVV), a member of the Picornaviridae family, is an oncolytic RNA virus that can cause idiopathic vesicular disease and increase mortality in newborn piglets. Although research on the pathogenic characteristics, epidemiology, pathogenic mechanism, and clinical diagnosis of SVA has increased due to its emergence and prevalence, the interaction between SVA and its host lncRNA has not been fully studied. This study used qualcomm sequencing to analyze differentially expressed lncRNAs and found that during SVA infection, lncRNA 8244 was significantly down-regulated in both PK-15 cells and piglets. Further analysis through quantitative real-time PCR and dual luciferase experiments demonstrated that lncRNA8244 could compete with ssc-miR-320 to regulate the expression of CCR7. The lncRNA824-ssc-miR-320-CCR7 axis activated the TLR-mediated signaling pathway, which recognized viral molecules and induced the expression of IFN-β. These findings provide new insight into the interaction between lncRNA and SVA infection, which could lead to a better understanding of SVA pathogenesis and contribute to the prevention and control of SVA disease.

When piglets are infected by virulent and avirulent strains of swine acute diarrhea syndrome coronavirus (SADS−CoV), there are obvious differences in their clinical symptoms; however, the specific mechanisms of pathogenicity and the immune regulation of highly pathogenic and low pathogenic strains are unknown. We collected intestinal tissues from SADS−CoV−infected piglets, performed a whole transcriptome sequencing analysis, including mRNA, miRNA, lncRNA, cicrRNA, and TUCP, and performed functional and correlation analyses of differentially expressed RNAs. Our results showed that the differentially expressed RNAs in group A versus group B (AvsB), group A versus group C (AvsC), and group B versus group C (BvsC) were relevant to immune and disease−related signaling pathways that participate in the organisms’ viral infection and immune regulation. Furthermore, data obtained from the HAllA analysis suggested that there was a strong correlation between the differentially expressed RNAs. Specifically, LNC_011487 in the P set was significantly negatively correlated with ssc−miR−215, and LNC_011487 was positively correlated with PI3. Moreover, we also constructed a differentially expressed RNA association network map. This study provides a valuable resource for studying the SADS−CoV transcriptome and pathogenic mechanism from the perspective of RNA to understand the differences in and consistency of the interaction between virulent and attenuated SADS−CoV strains and hosts.