scholarly journals Induction of Oxidative DNA Damage in Bovine Herpesvirus 1 Infected Bovine Kidney Cells (MDBK Cells) and Human Tumor Cells (A549 Cells and U2OS Cells)

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 393 ◽  
Author(s):  
Liqian Zhu ◽  
Xiaotian Fu ◽  
Chen Yuan ◽  
Xinyi Jiang ◽  
Gaiping Zhang
Keyword(s):  
Dna Damage ◽  
Virus Infection ◽  
Tumor Cells ◽  
Oxidative Dna Damage ◽  
A549 Cells ◽  
Human Tumor ◽  
Human Tumor Cells ◽  
Bovine Herpesvirus 1 ◽  
Mdbk Cells ◽  
Herpesvirus 1

Bovine herpesvirus 1 (BoHV-1) is an important pathogen of cattle that causes lesions in mucosal surfaces, genital tracts and nervous systems. As a novel oncolytic virus, BoHV-1 infects and kills numerous human tumor cells. However, the mechanisms underlying the virus-induced cell damages are not fully understood. In this study, we demonstrated that virus infection of MDBK cells induced high levels of DNA damage, because the percentage of comet tail DNA (tailDNA%) determined by comet assay, a direct indicator of DNA damage, and the levels of 8-hydroxyguanine (8-oxoG) production, an oxidative DNA damage marker, consistently increased following the virus infection. The expression of 8-oxoguanine DNA glycosylase (OGG-1), an enzyme responsible for the excision of 8-oxoG, was significantly decreased due to the virus infection, which corroborated with the finding that BoHV-1 infection stimulated 8-oxoG production. Furthermore, the virus replication in human tumor cells such as in A549 cells and U2OS cells also induced DNA damage. Chemical inhibition of reactive oxidative species (ROS) production by either ROS scavenger N-Acetyl-l-cysteine or NOX inhibitor diphenylene iodonium (DPI) significantly decreased the levels of tailDNA%, suggesting the involvement of ROS in the virus induced DNA lesions. Collectively, these results indicated that BoHV-1 infection of these cells elicits oxidative DNA damages, providing a perspective in understanding the mechanisms by which the virus induces cell death in both native host cells and human tumor cells.

scholarly journals The Role of Epidermal Growth Factor Receptor Signaling Pathway during Bovine Herpesvirus 1 Productive Infection in Cell Culture

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 927
Author(s):  
Wencai Qiu ◽  
Long Chang ◽  
Yongming He ◽  
Liqian Zhu
Keyword(s):  
Virus Infection ◽  
A549 Cells ◽  
Growth Factor Receptor ◽  
Specific Inhibitor ◽  
Productive Infection ◽  
Egfr Signaling ◽  
Bovine Herpesvirus 1 ◽  
Mdbk Cells ◽  
Epidermal Growth ◽  
Herpesvirus 1

Accumulating studies have shown that the epidermal growth factor receptor (EGFR) signaling pathway plays an essential role in mediating cellular entry of numerous viruses. In this study, we report that bovine herpesvirus 1 (BoHV-1) productive infection in both the human lung carcinoma cell line A549 and bovine kidney (MDBK) cells leads to activation of EGFR, as demonstrated by the increased phosphorylation of EGFR at Tyr1068 (Y1068), which in turn plays important roles in virus infection. A time-of-addition assay supported that virus replication at post-entry stages was affected by the EGFR specific inhibitor Gefitinib. Interestingly, both phospholipase C-γ1 (PLC-γ1) and Akt, canonical downstream effectors of EGFR, were activated following virus infection in A549 cells, while Gefitinib could inhibit the activation of PLC-γ1 but not Akt. In addition, virus titers in A549 cells was inhibited by chemical inhibition of PLC-γ1, but not by the inhibition of Akt. However, the Akt specific inhibitor Ly294002 could significantly reduce the virus titer in MDBK cells. Taken together, our data suggest that PLC-γ1 is stimulated in part through EGFR for efficient replication in A549 cells, whereas Akt can be stimulated by virus infection independent of EGFR, and is not essential for virus productive infection, indicating that Akt modulates BoHV-1 replication in a cell type-dependent manner. This study provides novel insights on how BoHV-1 infection activates EGFR signaling transduction to facilitate virus replication.

Dose-Rate Effect for DNA Damage Induced by Ionizing Radiation in Human Tumor Cells

1994 ◽  
Vol 138 (1) ◽  
pp. S93 ◽  
Author(s):  
J. M. Ruiz de Almodóvar ◽  
C. Bush ◽  
J. H. Peacock ◽  
G. G. Steel ◽  
S. J. Whitaker ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Dose Rate ◽  
Tumor Cells ◽  
Human Tumor ◽  
Rate Effect ◽  
Human Tumor Cells ◽  
Dose Rate Effect

Tumor-targeted oncolytic adenovirus demonstrates high cytotoxicity for human lung and renal cell carcinomas independently of the level of tumor PD-L1 expression.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3596-3596
Author(s):  
Jia Yao ◽  
Svetlana Atasheva ◽  
Cedrick Young ◽  
Viraj A. Master ◽  
Dmitry Shayakhmetov
Keyword(s):  
Virus Infection ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cell Lines ◽  
Oncolytic Virus ◽  
Human Tumor ◽  
Oncolytic Adenovirus ◽  
Human Tumor Cells ◽  
Highly Sensitive ◽  
Clinical Benefits

3596 Background: Immuno-checkpoint (IC) inhibitors targeting PD1-PD-L1 pathway have proven highly effective at extending survival of cancer patients. However, the clinical benefits of IC inhibitors are limited to only about 20% patients who have moderate to high levels of tumor PD1 and/or PD-L1 expression. To develop therapeutics that would provide clinical benefits to a larger proportion of cancer patients, we engineered oncolytic adenovirus for targeted infection of human tumor cells via CD46 and integrins of α3β1 or α6β4 classes, overexpressed on many epithelial human cancers. Methods: Here, we analyzed the infectivity and cytotoxicity of this novel oncolytic virus in a panel of human non-small cell lung cancers (NCSLC) cell lines, primary patient derived NSCLC xenografts, and tumor surgical explants from patients with renal cell carcinoma (RCC). Results: The in vitro analysis of NSCLC cells lines (N = 17) demonstrated that over 60% of them were highly sensitive to virus infection. The genome-wide transcriptional profiling showed that only 3 out of 12 cell lines that were sensitive to oncolytic virus infection, expressed PD-L1 ( > 4.5 Log2 RPMK). Furthermore, although the pre-treatment of these cell lines with IFN-I activated PD-L1 expression, IFN-I treatment did not reduce the efficacy of tumor cell infection by the oncolytic virus. The analysis of virus infectivity on primary human tumor cells from patients with NSCLC (N = 4) and RCC (N-24) demonstrated that primary tumors were highly sensitive to oncolytic virus infection. Specifically, tumor-targeted oncolytic virus demonstrated strong cytotoxicity in 22 out of 24 analyzed primary isolated RCC cell samples. Next, we subcutaneously grafted PD-L1-negative NSCLC A549 cells to NSG mice, treated them with oncolytic virus intravenously, and the kinetics of tumor growth and animal survival was monitored. This analysis showed that after intravenous administration, oncolytic virus was able to infect tumor cells and suppress tumor growth. Whereas the median survival in mock-treated group was 26 days, all mice survived up to 100 days post oncolytic virus therapy (endpoint). Conclusions: Our study showed that tumor-targeted oncolytic adenovirus infects human tumor cell lines independently of their PD-L1 expression status and is not sensitive to IFN-I inhibition. This novel tumor-targeted oncolytic virus has the potential to provide clinical benefits to cancer patients, who do not respond or became resistant to ICI drugs.

scholarly journals Mechanism and pharmacological specificity of dUTPase-mediated protection from DNA damage and cytotoxicity in human tumor cells

1998 ◽  
Vol 42 (5) ◽  
pp. 357-362 ◽  
Author(s):  
Leslie A. Parsels ◽  
Joshua D. Parsels ◽  
Lois M. Wagner ◽  
Tania L. Loney ◽  
Eric H. Radany ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tumor Cells ◽  
Human Tumor ◽  
Human Tumor Cells

scholarly journals The canonical NF-κB pathway differentially protects normal and human tumor cells from ROS-induced DNA damage

2012 ◽  
Vol 24 (11) ◽  
pp. 2007-2023 ◽  
Author(s):  
Alexandros Sfikas ◽  
Christina Batsi ◽  
Evangelia Tselikou ◽  
George Vartholomatos ◽  
Nikolaos Monokrousos ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tumor Cells ◽  
Human Tumor ◽  
Human Tumor Cells

scholarly journals A Novel Role for Pyruvate Kinase M2 as a Corepressor for P53 during the DNA Damage Response in Human Tumor Cells

2016 ◽  
Vol 291 (50) ◽  
pp. 26138-26150 ◽  
Author(s):  
Li Xia ◽  
Xin-Ran Wang ◽  
Xiao-Ling Wang ◽  
Su-Hui Liu ◽  
Xiao-Wei Ding ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tumor Cells ◽  
Pyruvate Kinase ◽  
Dna Damage Response ◽  
Human Tumor ◽  
Human Tumor Cells ◽  
Pyruvate Kinase M2 ◽  
Damage Response
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