Internalization of the dengue virus is cell cycle modulated in HepG2, but not vero cells

Phoolcharoen, Waranyoo; Smith, Duncan R.

doi:10.1002/jmv.20195

Cited by 22 publications

(11 citation statements)

References 45 publications

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“…However, DENV-2 infection was not found to affect the cell cycle in either of these two cell types. A study examining the effect of the cell cycle on DENV replication showed that the effects may be cell type specific [80], which may explain the results of this study using DENV-2 infected A549 cells. For a number of other viruses it has been shown that viral replication arrests the cell cycle at the G2/M transition, including HCV [81]–[83].…”

Section: Resultsmentioning

confidence: 63%

High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells

et al. 2014

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Disease caused by dengue virus is a global health concern with up to 390 million individuals infected annually worldwide. There are no vaccines or antiviral compounds available to either prevent or treat dengue disease which may be fatal. To increase our understanding of the interaction of dengue virus with the host cell, we analyzed changes in the proteome of human A549 cells in response to dengue virus type 2 infection using stable isotope labelling in cell culture (SILAC) in combination with high-throughput mass spectrometry (MS). Mock and infected A549 cells were fractionated into nuclear and cytoplasmic extracts before analysis to identify proteins that redistribute between cellular compartments during infection and reduce the complexity of the analysis. We identified and quantified 3098 and 2115 proteins in the cytoplasmic and nuclear fractions respectively. Proteins that showed a significant alteration in amount during infection were examined using gene enrichment, pathway and network analysis tools. The analyses revealed that dengue virus infection modulated the amounts of proteins involved in the interferon and unfolded protein responses, lipid metabolism and the cell cycle. The SILAC-MS results were validated for a select number of proteins over a time course of infection by Western blotting and immunofluorescence microscopy. Our study demonstrates for the first time the power of SILAC-MS for identifying and quantifying novel changes in cellular protein amounts in response to dengue virus infection.

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Section: Resultsmentioning

confidence: 63%

High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells

et al. 2014

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“…In the present study, the drastic reduction in cell viability in both infected MCF7 and MCF7-CR after 12 hpi was strongly suggestive of the involvement of cell cycle phases in the infectivity and cytotoxicity of NDV. Virus internalization was previously shown to be affected by these phases [30]. In addition, cisplatin resistance caused changes in cell cycle regulatory proteins which affect their way of responding to the drug [31].…”

Section: Discussionmentioning

confidence: 99%

Reduced Newcastle disease virus-induced oncolysis in a subpopulation of cisplatin-resistant MCF7 cells is associated with survivin stabilization

et al. 2012

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BackgroundCisplatin resistance is a serious problem in cancer treatment. To overcome it, alternative approaches including virotherapy are being pursued. One of the candidates for anticancer virotherapy is the Newcastle disease virus (NDV). Even though NDV's oncolytic properties in various cancer cells have been widely reported, information regarding its effects on cisplatin resistant cancer cells is still limited. Therefore, we tested the oncolytic efficacy of a strain of NDV, designated as AF2240, in a cisplatin-resistant breast cancer cell line.MethodsCisplatin-resistant cell line (MCF7-CR) was developed from the MCF7 human breast adenocarcinoma cell line by performing a seven-cyclic exposure to cisplatin. Following NDV infection, fluorescence-activated cell sorting (FACS) analysis and immunoblotting were used to measure cell viability and viral protein expression, respectively. Production of virus progeny was then assessed by using the plaque assay technique.ResultsInfection of a mass population of the MCF7-CR with NDV resulted in 50% killing in the first 12 hours post-infection (hpi), comparable to the parental MCF7. From 12 hpi onwards, the remaining MCF7-CR became less susceptible to NDV killing. This reduced susceptibility led to increased viral protein synthesis and virus progeny production. The reduction was also associated with a prolonged cell survival via stabilization of the survivin protein.ConclusionsOur findings showed for the first time, the involvement of survivin in the reduction of NDV-induced oncolysis in a subpopulation of cisplatin-resistant cells. This information will be important towards improving the efficacy of NDV as an anticancer agent in drug resistant cancers.

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“…These cells were chosen since cells of the hepatocyte lineage are implicated in the in vivo pathogenesis of DENV infection where patients with dengue fever and DHF often showed evidence of liver injury 10. Electron micrograph of HepG2 cells infected by dengue virus showed presence of intracellular virus particles originating from its replication site, the endoplasmic reticulum 11.…”

Section: Discussionmentioning

confidence: 99%

Antiviral actions of flavanoid-derived compounds on dengue virus type-2

Muhamad¹,

Kee²,

Rahman³

et al. 2010

Int. J. Biol. Sci.

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Dengue viruses, mosquito-borne members of the Flaviviridae family, are the causative agents of dengue fever and its associated complications, dengue haemorrhagic fever and dengue shock syndrome. To date, more than 2.5 billion people in over 100 countries are at risk of infection, and approximately 20 million infections were reported annually. There is currently no treatment or vaccine available for dengue infection. This study employed a whole-cell organism model or in vitro methods to study the inhibitory property of the flavanoid-derived compounds against DENV2 activity. Results showed that at concentration not exceeding the maximum non-toxic dose (MNTD), these compounds completely prevented DENV2 infection in HepG2 cells as indicated by the absence of cytophatic effects. The in vitro antiviral activity assessed in HepG2 cells employing virus inhibition assay showed high inhibitory activity in a dose dependent manner. At concentration below MNTD, compounds exhibited inhibitory activity against DENV2 with a range of potency strengths of 72% to 100%. The plaque forming unit per ml (pfu/ml) was reduced prominently with a maximum reduction of 98% when the infected HepG2 cells were treated with the highest non-toxic dose of compounds. The highly potent activity of the compounds against DENV2 infection strongly suggests their potential as a lead antiviral agent for dengue.

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Internalization of the dengue virus is cell cycle modulated in HepG2, but not vero cells

Cited by 22 publications

References 45 publications

High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells

High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells

Reduced Newcastle disease virus-induced oncolysis in a subpopulation of cisplatin-resistant MCF7 cells is associated with survivin stabilization

Antiviral actions of flavanoid-derived compounds on dengue virus type-2

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