Background: Marek's disease virus (MDV) is an oncogenic herpesvirus, which causes malignant lymphoma in chickens. The Meq protein of MDV, which is expressed abundantly in MDV-infected cells and in Marek's disease (MD) tumor cells, functions as a transcriptional activator and has been proposed to play an important role in oncogenic transformation. Preliminary studies demonstrated that Meq is able to bind p53 in vitro, as demonstrated using a protein-binding assay. This observation prompted us to examine whether the interaction between Meq and p53 occurs in cells, and to investigate the biological significance of this interaction. Results: We confirmed first that Meq interacted directly with p53 using a yeast two-hybrid assay and an immunoprecipitation assay, and we investigated the biological significance of this interaction subsequently. Exogenous expression of Meq resulted in the inhibition of p53-mediated transcriptional activity and apoptosis, as analyzed using a p53 luciferase reporter assay and a TUNEL assay. The inhibitory effect of Meq on transcriptional activity mediated by p53 was dependent on the physical interaction between these two proteins, because a Meq deletion mutant that lacked the p53-binding region lost the ability to inhibit p53-mediated transcriptional activity and apoptosis. The Meq variants L-Meq and S-Meq, but not VS-Meq and ∆Meq, which were expressed in MD tumor cells and MDV-infected cells, exerted an inhibitory effect on p53 transcriptional activity. In addition, ∆Meq was found to act as a negative regulator of Meq. Conclusions: The Meq oncoprotein interacts directly with p53 and inhibits p53-mediated transcriptional activity and apoptosis. These findings provide valuable insight into the molecular basis for the function of Meq in MDV oncogenesis.

The most important animal reservoirs ofSchistosoma japonicumin China are bovines. Diagnosis and control of bovine schistosomiasis is critical for reducing the prevalence of the disease. We screened defined diagnostic antigens that have the potential to increase the sensitivity and specificity of serological assays and to distinguish between active and prior infections. Five recombinant proteins with the potential to be diagnostic antigens were compared to the native soluble egg antigen preparation by enzyme-linked immunosorbent assay (ELISA). We evaluated the potentials of the recombinant proteins for discriminating active from prior infections, as well as the therapeutic efficacy of the established ELISA technique.

Schistosomiasis is a fatal zoonotic parasitic disease that also threatens human health. The main pathological features of schistosomiasis are granulomatous inflammation and subsequent liver fibrosis, which is a complex, chronic, and progressive disease. Extracellular vesicles (EVs) derived from schistosome eggs are broadly involved in host-parasite communication and act as important contributors to schistosome-induced liver fibrosis. However, it remains unclear whether substances secreted by the EVs of Schistosoma japonicum, a long-term parasitic “partner” in the hepatic portal vein of the host, also participate in liver fibrosis. Here, we report that EVs derived from S. japonicum worms attenuated liver fibrosis by delivering sja-let-7 into hepatic stellate cells (HSCs). Mechanistically, activation of HSCs was reduced by targeting collagen type I alpha 2 chain (Col1α2) and downregulation of the TGF-β/Smad signaling pathway both in vivo and in vitro. Overall, these results contribute to further understanding of the molecular mechanisms underlying host-parasite interactions and identified the sja-let-7/Col1α2/TGF-β/Smad axis as a potential target for treatment of schistosomiasis-related liver fibrosis.

Schistosomiasis is a chronic helminthic disease of both humans and animals and the second most prevalent parasitic disease after malaria. Through a complex migration process, schistosome eggs trapped in the liver can lead to the formation of granulomas and subsequent schistosome-induced liver damage, which results in high mortality and morbidity. Although praziquantel can eliminate mature worms and prevent egg deposition, effective drugs to reverse schistosome-induced liver damage are scarce. High mobility group box 1 (HMGB1) is a multifunctional cytokine contributing to liver injury, inflammation, and immune responses in schistosomiasis by binding to cell-surface Toll-like receptors and receptors for advanced glycation end products. HMGB1 is increased in the serum of patients with schistosomiasis and enables hepatic stellate cells to adopt a proliferative myofibroblast-like phenotype, which is crucial to schistosome-induced granuloma formation. Inhibition of HMGB1 was found to generate protective responses against fibrotic diseases in animal models. Clinically, HMGB1 presents a potential target for treatment of the chronic sequelae of schistosomiasis. Here, the pivotal role of HMGB1 in granuloma formation and schistosome-induced liver damage, as well the potential of HMGB1 as a therapeutic target, are discussed.

Schistosomiasis is a globally important helminthic disease of humans and animals, and it is the second most common parasitic disease after malaria. Eggs produced by mature females are responsible for the disease’s occurrence and spread. Frzb2, a secreted frizzled-related protein, can inhibit Wnt signalling by competitive binding to the specific frizzled protein receptor. In this study, the complete gene sequence of SjFrzb2 was obtained by using 3′-rapid amplification of cDNA ends technology. SjFrzb2 transcript levels at different stages of S. japonicum maturation were evaluated by quantitative real-time RT-PCR analysis. SjFrzb2 was expressed at all developmental stages examined and exhibited the highest transcription level in 7-day-old worms, then gradually decreased during the growth and developmental stages to reach the lowest level at 18 days post-infection. SjFrzb2 gene expression was higher in female worms than in male worms and was significantly higher in female worms from a single-sex infection than in female worms from a bisexual infection. The functions of SjFrzb2 were explored via a small interfering RNA-based gene silencing approach and the soaking method. The results showed that SjFrzb2 gene knockdown impaired the growth and development of S. japonicum in mice, affecting not only the survival and morphological structure of the worms but also their reproductive ability and the viability of the produced eggs. Collectively, these observations imply that Frzb2 may be a novel target for the development of immuno- and/or small molecule-based therapeutics to control schistosomiasis fecundity and transmission.