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

Zhu, Liqian; Fu, Xiaotian; Yuan, Chen; Jiang, Xinyi; Zhang, Gaiping

doi:10.3390/v10080393

Cited by 16 publications

(18 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that the canonical EGFR downstream effects including PLC-γ1, MAPK, Akt and JNK are unanimously activated during BoHV-1 productive infection in MDBK cells [19,20], we hypothesized that BoHV-1 infection activates EGFR signaling to facilitate viral replication. Furthermore, it has been reported that EGFR is activated in response to radiation-induced DNA damage to promote cell survival [21], and in BoHV-1-infected A549 cells, detectable DNA damage is induced at 24 and 48 hours (h) after infection [22]. As such, this work supports that EGFR is concomitantly activated at late stages of infection.…”

Section: Introductionsupporting

confidence: 77%

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

Qiu

Chang

et al. 2020

Viruses

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionsupporting

confidence: 77%

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

Qiu

Chang

et al. 2020

Viruses

Self Cite

View full text Add to dashboard Cite

show abstract

“…The induction of ROS has been claimed to be the underlying modality for various anti-cancer therapies that trigger apoptotic cell death in different cancer cells (Liou and Storz, 2010, Zhu et al, 2018). To further confirm apoptotic cell death caused by oncolytic NDV, we evaluated whether NDV-induced apoptosis in TC-1 cells was also related with enhanced ROS levels by quantifying intracellular ROS concentrations with DCFH-DA-based flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

Oncolytic Newcastle disease virus reduces growth of cervical cancer cell by inducing apoptosis

Keshavarz

Nejad

Esghaei

et al. 2020

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

Although Oncolytic viruses have been regarded as a promising tool for targeted therapy of cancer, accomplishing high efficacy and specificity with this strategy is challenging. Oncolytic virotherapy is one of the novel therapeutic methods recently used for the therapy of human malignancies. Cervical cancer is on the major public health problem and the second most common cause of cancer death among females in less developed countries. The aim of this study was mainly to determine the apoptosis effect of oncolytic Newcastle disease virus (NDV) in TC-1 cell line.In the current study, the oncolytic NDV, vaccine strain LaSota, was used to infect murine TC-1 cells of human papillomavirus (HPV)-associated carcinoma which expressing human papillomavirus 16 (HPV-16) E6/E7 antigens in vitro. The effectiveness of NDV for cervical cancer cell line was investigated by evaluating the antitumor activity of oncolytic NDV and the involved mechanisms. Antitumor activities of oncolytic NDV were assessed by cell proliferation (MTT) and lactate dehydrogenase (LDH) release analysis. In addition, molecular changes of early stage of apoptosis and the role of reactive oxygen species (ROS) were analyzed by flow cytometry and Western Blot in NDV-treated TC-1 cells.The results showed that NDV treatment significantly decreased the viability of a TC-1 cell line and suppressed the growth by inducing apoptotic cell death. In addition, we demonstrated that NDV-induced apoptosis of TC-1 cells is mediated by ROS production. In summary, our findings suggest that oncolytic NDV is a possible therapeutic candidate as a selective antitumor agent for the treatment of cervical cancer.

show abstract

“…NADPH oxidases (NOXs) are responsible for transporting electrons across biological membranes to generate ROS [29, 30]. BoHV-1 infection-induced excessive production of ROS is significantly decreased by NOX inhibitor DPI [9, 23, 31]. We initially detected whether ROS generation was stimulated in the context of the virus infection at an MOI of 1 for 16 hours.…”

Section: Resultsmentioning

confidence: 99%

“…It has been reported that the oxidants such as tertiary butyl hydroperoxide (t-BOOH), an ROS mimic, increase cellular NRF1 and TFAM gene expression in rat liver cells and hepatoma cells [45, 46]. We therefore investigated whether ROS are involved in the regulation of NRF1/2 and TFAM expressions using the NOX inhibitor DPI, which has been confirmed to block ROS production ([31] and Figure 4(a)). The enhanced expression of NRF2 but not NRF1 by DPI treatment in the mock-infected cells (Figures 4(c), 4(d), and 4(f)) indicated that ROS may partially regulate the expression of NRF2 but not NRF1.…”

Section: Discussionmentioning

confidence: 99%

The Differential Expression of Mitochondrial Function-Associated Proteins and Antioxidant Enzymes during Bovine Herpesvirus 1 Infection: A Potential Mechanism for Virus Infection-Induced Oxidative Mitochondrial Dysfunction

Jiang

Chen

et al. 2019

Mediators of Inflammation

Self Cite

View full text Add to dashboard Cite

Reactive oxidative species (ROS) are important inflammatory mediators. Electrons escaping from the mitochondrial electron transport chain (ETC) during oxidative phosphorylation (OXPHOS) in the mitochondrial respiratory chain (RC) complexes contribute to ROS production. The cellular antioxidant enzymes are important for maintaining ROS release at the physiological levels. It has been reported that BoHV-1 infection induces overproduction of ROS and oxidative mitochondrial dysfunction in cell cultures. In this study, we found that chemical interruption of RC complexes by TTFA (an inhibitor of RC complex II), NaN3 (an inhibitor of RC complex IV), and oligomycin A (an inhibitor of ATP synthase) consistently decreased virus productive infection, suggesting that the integral processes of RC complexes are important for the virus replication. The virus infection significantly increased the expression of subunit SDHB (succinate dehydrogenase) and MTCO1 (cytochrome c oxidase subunit I), critical components of RC complexes II and IV, respectively. The expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, catalase (CAT), and glutathione peroxidase 4 (GPX4) was differentially affected following the virus infection. The protein TFAM (transcription factor A, mitochondrial) stimulated by either nuclear respiratory factor 1 (NRF1) or NRF2 is a key regulator of mitochondrial biogenesis. Interestingly, the virus infection at the late stage (at 16 h after infection) stimulated TFAM expression but decreased the levels of both NRF1 and NRF2, indicating that virus infection activated TFAM signaling independent of either NRF1 or NRF2. Overall, this study provided evidence that BoHV-1 infection altered the expression of molecules associated with RC complexes, antioxidant enzymes, and mitochondrial biogenesis-related signaling NRF1/NRF2/TFAM, which correlated with the previous report that virus infection induces ROS overproduction and mitochondrial dysfunction.

show abstract

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

Cited by 16 publications

References 51 publications

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

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

Oncolytic Newcastle disease virus reduces growth of cervical cancer cell by inducing apoptosis

The Differential Expression of Mitochondrial Function-Associated Proteins and Antioxidant Enzymes during Bovine Herpesvirus 1 Infection: A Potential Mechanism for Virus Infection-Induced Oxidative Mitochondrial Dysfunction

Contact Info

Product

Resources

About