Analysis of gene mutation in the interaction domain of head and stalk of Newcastle disease virus hemagglutinin-neuraminidase glycoprotein / 中华实验和临床病毒学杂志

Objective@#To identify the function of 91-112 amino acids (aa) fragment, the interaction domain of head and stalk of Newcastle disease virus(NDV) HN glycoprotein, and clarify the role of the fragment in promoting cell specific membrane fusion.@*Methods@#The specific gene sequences were identified by aligning 91-112 amino acids of NDV HN protein with amino acids of MeV H, RSV G, hPIV3 HN protein. The fragment deletion, fragment substitution and intermolecular homologous recombination method were combined to construct the deletion mutant, De(HN), and three chimeras, Ch(MeV), Ch(RSV), Ch(hPIV3). Cationic transfection reagent was used to transfect the plasmids into baby hamster kidney cells (BHK-21), in which vaccinia virus-T7 RNA polymerase expression system was expressed. Indirect immunofluorescence assay (IIFA) and flow cytometry (FCM) were executed to analyze the cell surface expression level. Cell fusion promotion activity, receptor recognition activity and neuraminidase activity of each mutant were also detected.@*Results@#Cell surface expression efficiency of De(HN) and Ch(MeV), Ch(RSV), Ch(hPIV3) proteins were 9.04%, 82.20%, 70.16%, 75.65% of that of wild-type (wt) HN. Fusion promotion activity of De(HN), Ch(MeV), Ch(RSV), Ch(hPIV3) were 3.83%, 24.76%, 29.42%, 57.84% of that of wt HN. The fusion promotion activity of De(HN) almost disappeared and syncytium couldn’t be found under the microscope. Hemadsorption activity was 13.48%, 36.25%, 34.93%, 65.22%, respectively (P<0.05), which was consistent with the fusion promotion activity of mutant proteins. Neuraminidase activity was 10.81%, 54.42%, 50.13%, 60.35% of that of wt HN, respectively (P<0.05).@*Conclusions@#The amino acids fragment (91-112) of NDV HN protein plays an important role in promotion fusion. The loss of fusion promotion activity of De(HN) protein was related to the failure of effective cell surface expression of the mutant.

Progress in application of Newcastle disease virus for anti-tumor therapy / 中华实验和临床病毒学杂志

Oncolytic virus therapy is becoming a new direction for cancer treatment, which could take the advantage of the characteristic of oncolytic virus selectively replicating in cancer cells, and killing tumor cells without damaging normal cells. Compared with conventional chemotherapy or radiotherapy, it has higher specificity, fewer side effects and the ability resisting various kinds of malignant tumors. Newcastle disease virus, a typical oncolytic virus, can cause Newcastle disease in poultry. However, no serious symptoms occurred after human being infected with NDV. With the development of reverse genetics technology, it is possible to enhance the anti-tumor activity of NDV by promoting membrane fusion and apoptosis with gene recombination. The review is about the recent research progress in vitro and in vivo oncolytic experiments and clinical application of NDV at home and abroad, which aimed at providing scientific reference for the anti-tumor study of NDV in the future.