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Newcastle disease virus (NDV) is an oncolytic virus whose F protein cleavage activity is associated with viral infectivity. To explore the potential of modifying F protein cleavage activity to enhance antitumor effects, we constructed a recombinant NDV LaSota strain by replacing its F protein cleavage site with that from the mesogenic Beaudette C (BC) strain using reverse genetics techniques. The resulting virus, rLaSota-BC-RFP, demonstrated significantly enhanced infectivity and tumor cell suppression on the murine melanoma B16F10 cell, characterized by higher cytotoxicity and increased apoptosis compared to its parental strain, rLaSota-RFP. In vivo, rLaSota-BC-RFP treatment of B16F10 tumors in C57BL/6 mice resulted in significant tumor growth inhibition, improved survival rate, and induction of tumor-specific apoptosis and necrosis. Additionally, the rLaSota-BC-RFP treatment enhanced immunostimulatory effects within the tumor microenvironment (TME), characterized by increased infiltration of CD4+ and CD8+ T cells and elevated levels of antitumor immune modulator cytokines, including mouse IL-12, IFN-γ, IL-15, and TNF-α, in the rLaSota-BC-RFP-treated tumor tissues. Collectively, these findings demonstrate that the mesogenic F protein cleavage site enhances the oncolytic potential of the NDV LaSota strain, suggesting that rLaSota-BC-RFP is a promising oncolytic viral vector for gene delivery in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The thermal reservoir in Taiyun area mainly consists of Ordovician and Cambrian carbonate formations. The target interval of example well contains more than 95% carbonate, being thick, argilliferous and have well-developed natural fissures and rich hot water. However, sometimes stimulation is necessary to achieve the designed water production rate. In this paper, multistage alternating injection acid fracturing technology is selected according to lithologic characteristics of geothermal reservoir. A gel acid, which is a composite of 20%HCl+0.8%SHY1+2% corrosion inhibitor+1.5% iron ion stabilizer+1% cleanup additive, is optimized and developed by experimental tests. Its viscosity can reach 27 mPa·s. Then, pumping schedule of multi-stage alternate injection acid fracturing is optimized by numerical simulator of acid fracturing design. It is shown from job pressure of field sample well that resistance reduction ability of gel acid needs to be further improved. Moreover, from the analysis results of pressure decline after acid fracturing, the fluid efficiency is 42.32%, net pressure is 3.3 MPa, and the dynamic fracture length is 107m, the maximum fracture width is 8.6mm by fitting treatment pressure. The water production increase factor reaches 1.2 after acid fracturing treatment. Therefore, the acid fracturing treatment is successful.

Abstract Background Avian metapneumovirus subtype C (aMPV/C) causes severe upper respiratory disease in turkeys. Previous report revealed the presence of aMPV/C in wild birds in the southeast regions of the U.S. Methods In this study, aMPV/C positive oral swabs from American coots (AC) and Canada geese (CG) were passaged three times in the respiratory tract of specific pathogen free (SPF) turkeys and used as aMPV/C P3 virus isolates in subsequent studies. Results Wild bird P3 isolates showed similar growth characteristics when compared to virulent aMPV/C in chicken embryo fibroblast ( CEF) cell cultures and their glycoprotein G gene sequence was closely related to the G gene of aMPV/C Colorado reference virus. Three-day-old commercial or SPF turkeys were inoculated oculonasally with wild bird aMPV/C P3 isolates. At 5 and 7 days post-inoculation (DPI), severe clinical signs were observed in both of the AC and CG virus-exposed groups. Viral RNA was detected in tracheal swabs by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, immunohistochemistry showed virus replication in the nasal turbinate and trachea. All virus-exposed turkeys developed positive antibody response by 14 DPI. Conclusions Our data demonstrate that aMPV/C wild bird isolates induced typical aMPV/C disease in the domestic turkeys.

Abstract Background Many viruses have evolved multiple strategies to prevent super infection of host cells by more than one virion. This phenomenon, known as super infection exclusion, may play an important role on virus evolution because it can affect the frequency of reassortment and/or recombination. Newcastle disease virus (NDV), a negative sense single-stranded RNA virus, is characterized by its continuous evolutionary dynamics and by a low frequency of recombination events. However, the mechanisms that contribute to the low recombination rates on NDV are still not completely understood. Methods In this study we assessed the ability of two NDV strains (LaSota and B1) to super infect host cells in vitro. We generated a recombinant NDV strain LaSota expressing the red fluorescent protein (RFP) and used it in co-infection assays with a related NDV strain B1 expressing the green fluorescent protein (GFP). DF-1 cells were inoculated with both viruses at the same time or at different intervals between primary infection and super infection. Results When both viruses were inoculated at the same time point, a 27% co-infection rate was observed, whereas when they were inoculated at different time points the super infection rates decreased to levels as low as 1.4%. Conclusions These results indicate that although different NDV strains can co-infect host cells in vitro, the super infection rates are low, specially as the time between the primary infection and super infection increases. These results confirm the occurrence of super infection exclusion between different strains of NDV.

Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. However, the potential oncolytic ability of the recombinant newcastle disease virus (NDV) Anhinga strain carried with tumor necrosis factor‐related apoptosis inducing ligand (TRAIL) has not been fully explored at present. In the present study, the recombinant NDV/Anh‐TRAIL that secretes soluble TRAIL was constructed and the experiment results suggested NDV/Anh‐TRAIL as a promising candidate for glioma therapy. Growth kinetic and TRAIL secreted quantity of recombinant NDV/Anh‐TRAIL virus were measured. Cytotoxic and cell apoptosis were analyzed for its anti‐glioma therapy in vitro. Nude mice were used for the in vivo evaluation. Both tumor volume and mice behavior after injection were observed. The recombinant virus replicated with the same kinetics as the parental virus and the highest expression of TRAIL (77.8 ng/L) was found at 48 hours. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, a tetrazole and flow cytometry data revealed that the recombinant NDV/Anh‐TRAIL (56.1 ± 8.2%) virus could induce a more severe apoptosis rate, when compared with the NDV wild type (37.2 ± 7.0%) and mock (7.0 ± 1.8%) groups (P <.01), in U251 cells. Furthermore, in the present animal study, the average tumor volume was smaller in the NDV/Anh‐TRAIL group (97.21 mm3), when compared with the NDV wild type (205.03 mm3, P <.05) and PBS (310.30 mm3, P <.01) groups. Highlights: NDV/Anh‐TRAIL exerts an obvious result in U251 glioma therapeutic effect in vitro and in vivo. Anhinga strain could be an effectual vector for tumor therapy. NDV/Anh‐TRAIL could become a potent candidate for clinical treatment especially for glioma. [ABSTRACT FROM AUTHOR]