scholarly journals Exosomes Carry microRNAs into Neighboring Cells to Promote Diffusive Infection of Newcastle Disease Virus

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 527 ◽  
Author(s):  
Changluan Zhou ◽  
Lei Tan ◽  
Yingjie Sun ◽  
Xusheng Qiu ◽  
Chunchun Meng ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Hela Cells ◽  
Newcastle Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Infections ◽  
Bioactive Substances ◽  
Cytopathic Effects

Newcastle disease virus (NDV), an avian paramyxovirus, was shown to prefer to replicate in tumor cells instead of normal cells; however, this mechanism has not been fully elucidated. Exosomes play a crucial role in intercellular communication due to the bioactive substances they carry. Several studies have shown that exosomes are involved in virus infections. However, the effect that exosomes have on NDV-infected tumor cells is not known. In this study, we focus on the role of exosomes secreted by NDV-infected HeLa cells in promoting NDV replication. Three miRNA candidates (miR-1273f, miR-1184, and miR-198) embraced by exosomes were associated with enhancing NDV-induced cytopathic effects on HeLa cells. Furthermore, luciferase assays, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA) all demonstrated that these miRNAs could suppress interferon (IFN)-β gene expression. Enhanced NDV replication in HeLa cells was identified by Western blot and plaque assays. Based on these results, we speculate that NDV employed exosomes entry into neighboring cells, which carry miRNAs, resulting in inhibition of the IFN pathway and promotion of viral infection. To our knowledge, this is the first report on the involvement of NDV-employed exosomes in tumor cells, and as such, it provides new insights into the development of anti-tumor therapies.

scholarly journals Differential microRNA Expression in Newcastle Disease Virus-Infected HeLa Cells and Its Role in Regulating Virus Replication

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu Chen ◽  
Shanshan Zhu ◽  
Yuru Pei ◽  
Jiao Hu ◽  
Zenglei Hu ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Virus Replication ◽  
Expression Profile ◽  
Deep Sequencing ◽  
Hela Cells ◽  
Mirna Expression ◽  
Newcastle Disease ◽  
Mirna Expression Profile

As an oncolytic virus, Newcastle disease virus (NDV) can specifically kill tumor cells and has been tested as an attractive oncolytic agent for cancer virotherapy. Virus infection can trigger the changes of the cellular microRNA (miRNA) expression profile, which can greatly influence viral replication and pathogenesis. However, the interplay between NDV replication and cellular miRNA expression in tumor cells is still largely unknown. In the present study, we compared the profiles of cellular miRNAs in uninfected and NDV-infected HeLa cells by small RNA deep sequencing. Here we report that NDV infection in HeLa cells significantly changed the levels of 40 miRNAs at 6 h post-infection (hpi) and 62 miRNAs at 12 hpi. Among 23 highly differentially expressed miRNAs, NDV infection greatly promoted the levels of 3 miRNAs and suppressed the levels of 20 miRNAs at both time points. These 23 miRNAs are predicted to target various genes involved in virus replication and antiviral immunity such as ErbB, Jak-STAT, NF-kB and RIG-I-like receptor. Verification of deep sequencing results by quantitative RT-PCR showed that 9 out of 10 randomly selected miRNAs chosen from this 23-miRNA pool were consistent with deep sequencing data, including 6 down-regulated and 3 up-regulated. Further functional research revealed that hsa-miR-4521, a constituent in this 23-miRNA pool, inhibited NDV replication in HeLa cells. Moreover, dual-luciferase and gene expression array uncovered that the member A of family with sequence similarity 129 (FAM129A) was directly targeted by hsa-miR-4521 and positively regulated NDV replication in HeLa cells, indicating that hsa-miR-4521 may regulate NDV replication via interaction with FAM129A. To our knowledge, this is the first report of the dynamic cellular miRNA expression profile in tumor cells after NDV infection and may provide a valuable basis for further investigation on the roles of miRNAs in NDV-mediated oncolysis.

scholarly journals Role of the chicken oligoadenylate synthase-like gene during in vitro Newcastle disease virus infection

2021 ◽  
Vol 100 (5) ◽  
pp. 101067
Author(s):  
Ana Paula Del Vesco ◽  
Hyun Jun Jang ◽  
Melissa S. Monson ◽  
Susan J. Lamont
Keyword(s):  
Virus Infection ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Newcastle Disease Virus Infection

Tumor selective replication of Newcastle disease virus: Association with defects of tumor cells in antiviral defence

2006 ◽  
Vol 119 (2) ◽  
pp. 328-338 ◽  
Author(s):  
Christoph Fiola ◽  
Ben Peeters ◽  
Philippe Fournier ◽  
Annette Arnold ◽  
Mariana Bucur ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Tumor Selective

scholarly journals Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Seyed Mohammad Miri ◽  
Mir Saeed Ebrahimzadeh ◽  
Elahe Abdolalipour ◽  
Mahsa Yazdi ◽  
Hassan Hosseini Ravandi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Gene Therapy ◽  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Oncolytic Viruses

Abstract Background Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic membrane glycoproteins (FMGs) could facilitate viral propagation and increase the infection rate of tumor cells by oncolytic viruses. Additionally, immune checkpoint blockade has widely been investigated for its anti-tumor effects against several types of cancers. Here, we investigated for the first time whether the incorporation of influenza hemagglutinin-2 (HA2) FMG could improve the oncolytic characteristics of NDV against cervical cancer. Next, we added anti-PD-1 mAb to our therapeutic recipe to assess the complementary role of immune checkpoint blockade in curbing tumor progression. Methods For this purpose, TC-1 tumor cells were injected into the mice models and treatment with NDV, iNDV, HA2, NDV-HA2, iNDV-HA2 began 10 days after tumor challenge and was repeated at day 17. In addition, PD-1 blockade was conducted by injection of anti-PD-1 mAb at days 9 and 16. Two weeks after the last treatment, sample mice were sacrificed and treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, tumors condition was monitored weekly for 6 weeks intervals and the tumor volume was measured and compared within different groups. Results The results of co-treatment with NDV and HA2 gene revealed that these agents act synergistically to induce antitumor immune responses against HPV-associated carcinoma by enhancement of E7-specific lymphocyte proliferation, inducement of CD8+ T cell cytotoxicity responses, increase in splenic cytokines and granzyme B, decrease in immunosuppressive cytokines and E6 oncogene expression, and upregulation of apoptotic proteins expression, in comparison with control groups. Moreover, incorporation of PD-1 blockade as the third side of our suggested therapy led to noticeable regression in tumor size and augmentation of cytokine responses. Conclusions The invaluable results of synergy between NDV virotherapy and HA2 gene therapy suggest that tumor-selective cell killing by oncolytic NDV can be enhanced by combining with FMG gene therapy. Moreover, the adjunction of the PD-1 blockade proves that checkpoint blockade can be considered as an effective complementary therapy for the treatment of cervical cancer.

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