Human Gyrovirus-Apoptin Interferes with the Cell Cycle and Induces G2/M Arrest Prior to Apoptosis

Chaabane, Wiem; Ghavami, Saeid; Małecki, Andrzej; Łos, Marek

doi:10.1007/s00005-017-0464-8

Cited by 19 publications

(14 citation statements)

References 36 publications

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“…These homologs are distantly related each other, as they show a mean nucleotide diversity of 39.2% and a mean amino acid diversity of 47.7% for VP2 and of 61.3% for apoptin. Despite the diversity, the apoptin of Gyrovirus Tu789 is able to trigger apoptosis in cancer cell lines at levels comparable to the CAV apoptin (Bullenkamp et al, 2012;Chaabane et al, 2017).…”

Section: Computational Design Of New Variants Of the Apoptin From Chimentioning

confidence: 99%

New insights into the evolutionary features of viral overlapping genes by discriminant analysis

Pavesi

2020

Virology

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Please cite this article as: Pavesi, A., New insights into the evolutionary features of viral overlapping genes by discriminant analysis, Virology, https://doi. AbstractOverlapping genes originate by a mechanism of overprinting, in which nucleotide substitutions in a pre-existing frame induce the expression of a de novo protein from an alternative frame. In this study, I assembled a dataset of 319 viral overlapping genes, which included 82 overlaps whose expression is experimentally known and the respective 237 homologs. Principal component analysis revealed that overlapping genes have a common pattern of nucleotide and amino acid composition.Discriminant analysis separated overlapping from non-overlapping genes with an accuracy of 97%.When applied to overlapping genes with known genealogy, it separated ancestral from de novo frames with an accuracy close to 100%. This high discriminant power was crucial to computationally design variants of de novo viral proteins known to possess selective anticancer toxicity (apoptin) or protection against neurodegeneration (X protein), as well as to detect two new potential overlapping genes in the genome of the new coronavirus SARS-CoV-2.

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Section: Computational Design Of New Variants Of the Apoptin From Chimentioning

confidence: 99%

New insights into the evolutionary features of viral overlapping genes by discriminant analysis

Pavesi

2020

Virology

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“…9,12,[25][26][27] Recent studies indicated that CAV-Apoptin and HGV-Apoptin have similar mechanisms and they induce apoptosis in human tumor cells without the involvement of p53 via the intrinsic mitochondrial pathway. 19,20 It has been shown that the subcellular distribution pattern of HGV-Apoptin is the same as that observed in CAV-Apoptin, which localizes in the nuclei of cancer cells where it shows a granular distribution that later clusters to form aggregates, while it remains in the cytoplasm of normal human cells. 18 CAV-Apoptin is phosphorylated in threonine 108 mainly in tumor cells, but not in normal cells, which seems to be important in tumor-selective activation process.…”

Section: Figure 2 Transfection Efficiency Gfp Expression and In A549mentioning

confidence: 83%

“…To date, the apoptotic effects of HGV-apoptin are shown only on a few cell lines (HCT116 colon carcinoma, Saos-2 osteosarcoma, MCF-7 breast cancer cell lines). [18][19][20] In this study, we evaluated the apoptotic effects of this protein on A549 and HEK-293 cell lines and compared it with CAV-Apoptin, in order to provide further evidence regarding the cytotoxicity of HGV-apoptin in cancerous and normal cell lines.…”

Section: Figure 1 (A)mentioning

confidence: 99%

Human Gyrovirus Apoptin as a Potential Selective Anticancer Agent: An In Vitro Study

et al. 2019

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Background: Selective therapy has always been the main challenge in cancer treatments. Recently, it has been shown that Human Gyrovirus-derived protein apoptin (HGV-Apoptin) has selective cytotoxic effects on cancer cells similar to its homologue, Chicken Anemia Virus-derived Apoptin (CAV-Apoptin). However, apoptotic effects of Human Gyrovirus apoptin have been only evaluated on a few cancerous cell lines and need to be further investigated. In this study, we have evaluated the apoptotic effects of HGV-Apoptin and CAV-Apoptin expression on lung cancer (A549) and normal (HEK-293) cell lines, in order to provide more information about the specificity of these proteins on cancerous cells. Methods: Target cells were transfected by the calcium-phosphate precipitation method with constructed plasmids expressing HGV-Apoptin and CAV-Apoptin proteins as well as the control plasmid. Transfection efficiency was followed and imaged by fluorescence microscopy. Quantification of apoptosis was performed by flow cytometry. Measurements were compared by paired Student t-test. Results: Cells were successfully transfected with control and constructed plasmids. Flowcytometry analysis showed that A549 cells transfected with HGV-Apoptin and CAV-Apoptin expressing plasmids, undergone the apoptosis compared to A549 cells transfected with control plasmid (P<0.001). None of the plasmids could induce apoptosis in HEK-293 cells. Conclusion: Human Gyrovirus-derived apoptin (HGV-Apoptin) similar to its homologue, chicken anemia virus derived Apoptin (CAV-Apoptin) can induce apoptosis in Non-small-cell lung carcinoma cell line A549, but not in normal human embryonic kidney cell line HEK-293, which can be introduced as a promising novel specific antitumor agent.

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“…Manipulation of the cell cycle may induce or prevent apoptosis depending on the cellular context, but typically extended mitotic arrest ultimately results in cellular death [120,121]. Some of the viral proteins have been shown to induce cell cycle arrest at the G2/M phase including CAV and HGV-Apoptin, E4orf4 and NS1 in cancer cells [122][123][124][125]. Likewise, cells treated with apoptin display clear abnormal mitotic figures, which may explain the pause in this stage of the cell cycle [126].…”

Section: Perturbations Of the Cell Cyclementioning

confidence: 99%

“…One interesting theory for the mechanism of action of these viral proteins is the existence of a direct interaction with the APC/C and thus disturbing cell cycle progression and ultimately driving apoptosis. E4orf4 and Apoptin from both CAV and HGV has been shown to interact directly with subunits of the APC/C [122][123][124]. Although APC/C has not been studied in the context of E1A cancer cell toxicity, it has been shown that E1A interacts with APC components such as CBP/P300 in the context of viral transformation and likely has similar effects in tumour cells, so this link needs to be further explored [128,129].…”

Section: Perturbations Of the Cell Cyclementioning

confidence: 99%

Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death

Wyatt

Müller

Tavassoli

2019

Cancers

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Cell death is a tightly regulated process which can be exploited in cancer treatment to drive the killing of the tumour. Several conventional cancer therapies including chemotherapeutic agents target pathways involved in cell death, yet they often fail due to the lack of selectivity they have for tumour cells over healthy cells. Over the past decade, research has demonstrated the existence of numerous proteins which have an intrinsic tumour-specific toxicity, several of which originate from viruses. These tumour-selective viral proteins, although from distinct backgrounds, have several similar and interesting properties. Though the mechanism(s) of action of these proteins are not fully understood, it is possible that they can manipulate several cell death modes in cancer exemplifying the intricate interplay between these pathways. This review will discuss our current knowledge on the topic and outstanding questions, as well as deliberate the potential for viral proteins to progress into the clinic as successful cancer therapeutics.

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Human Gyrovirus-Apoptin Interferes with the Cell Cycle and Induces G2/M Arrest Prior to Apoptosis

Cited by 19 publications

References 36 publications

New insights into the evolutionary features of viral overlapping genes by discriminant analysis

New insights into the evolutionary features of viral overlapping genes by discriminant analysis

Human Gyrovirus Apoptin as a Potential Selective Anticancer Agent: An In Vitro Study

Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death

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