Evaluation and Prediction of the HIV-1 Central Polypurine Tract Influence on Foamy Viral Vectors to Transduce Dividing and Growth-Arrested Cells
Retroviral vectors are potent tools for gene delivery and various biomedical applications. To accomplish a gene transfer task successfully, retroviral vectors must effectively transduce diverse cell cultures at different phases of a cell cycle. However, very promising retroviral vectors based on the...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2014/487969 |
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| author | Sergey Shityakov Carola Förster Axel Rethwilm Thomas Dandekar |
| author_facet | Sergey Shityakov Carola Förster Axel Rethwilm Thomas Dandekar |
| author_sort | Sergey Shityakov |
| collection | DOAJ |
| description | Retroviral vectors are potent tools for gene delivery and various biomedical applications. To accomplish a gene transfer task successfully, retroviral vectors must effectively transduce diverse cell cultures at different phases of a cell cycle. However, very promising retroviral vectors based on the foamy viral (FV) backbone lack the capacity to efficiently transduce quiescent cells. It is hypothesized that this phenomenon might be explained as the inability of foamy viruses to form a pre-integration complex (PIC) with nuclear import activity in growth-arrested cells, which is the characteristic for lentiviruses (HIV-1). In this process, the HIV-1 central polypurine tract (cPPT) serves as a primer for plus-strand synthesis to produce a “flap” element and is believed to be crucial for the subsequent double-stranded cDNA formation of all retroviral RNA genomes. In this study, the effects of the lentiviral cPPT element on the FV transduction potential in dividing and growth-arrested (G1/S phase) adenocarcinomic human alveolar basal epithelial (A549) cells are investigated by experimental and theoretical methods. The results indicated that the HIV-1 cPPT element in a foamy viral vector background will lead to a significant reduction of the FV transduction and viral titre in growth-arrested cells due to the absence of PICs with nuclear import activity. |
| format | Article |
| id | doaj-art-3a9a380ce27444ed992820c053d940b0 |
| institution | Kabale University |
| issn | 2356-6140 1537-744X |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-3a9a380ce27444ed992820c053d940b02025-02-03T01:10:22ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/487969487969Evaluation and Prediction of the HIV-1 Central Polypurine Tract Influence on Foamy Viral Vectors to Transduce Dividing and Growth-Arrested CellsSergey Shityakov0Carola Förster1Axel Rethwilm2Thomas Dandekar3Department of Anesthesia and Critical Care, University of Würzburg, 97080 Würzburg, GermanyDepartment of Anesthesia and Critical Care, University of Würzburg, 97080 Würzburg, GermanyDepartment of Virology, University of Würzburg, 97074 Würzburg, GermanyDepartment of Bioinformatics, University of Würzburg, 97074 Würzburg, GermanyRetroviral vectors are potent tools for gene delivery and various biomedical applications. To accomplish a gene transfer task successfully, retroviral vectors must effectively transduce diverse cell cultures at different phases of a cell cycle. However, very promising retroviral vectors based on the foamy viral (FV) backbone lack the capacity to efficiently transduce quiescent cells. It is hypothesized that this phenomenon might be explained as the inability of foamy viruses to form a pre-integration complex (PIC) with nuclear import activity in growth-arrested cells, which is the characteristic for lentiviruses (HIV-1). In this process, the HIV-1 central polypurine tract (cPPT) serves as a primer for plus-strand synthesis to produce a “flap” element and is believed to be crucial for the subsequent double-stranded cDNA formation of all retroviral RNA genomes. In this study, the effects of the lentiviral cPPT element on the FV transduction potential in dividing and growth-arrested (G1/S phase) adenocarcinomic human alveolar basal epithelial (A549) cells are investigated by experimental and theoretical methods. The results indicated that the HIV-1 cPPT element in a foamy viral vector background will lead to a significant reduction of the FV transduction and viral titre in growth-arrested cells due to the absence of PICs with nuclear import activity.http://dx.doi.org/10.1155/2014/487969 |
| spellingShingle | Sergey Shityakov Carola Förster Axel Rethwilm Thomas Dandekar Evaluation and Prediction of the HIV-1 Central Polypurine Tract Influence on Foamy Viral Vectors to Transduce Dividing and Growth-Arrested Cells The Scientific World Journal |
| title | Evaluation and Prediction of the HIV-1 Central Polypurine Tract Influence on Foamy Viral Vectors to Transduce Dividing and Growth-Arrested Cells |
| title_full | Evaluation and Prediction of the HIV-1 Central Polypurine Tract Influence on Foamy Viral Vectors to Transduce Dividing and Growth-Arrested Cells |
| title_fullStr | Evaluation and Prediction of the HIV-1 Central Polypurine Tract Influence on Foamy Viral Vectors to Transduce Dividing and Growth-Arrested Cells |
| title_full_unstemmed | Evaluation and Prediction of the HIV-1 Central Polypurine Tract Influence on Foamy Viral Vectors to Transduce Dividing and Growth-Arrested Cells |
| title_short | Evaluation and Prediction of the HIV-1 Central Polypurine Tract Influence on Foamy Viral Vectors to Transduce Dividing and Growth-Arrested Cells |
| title_sort | evaluation and prediction of the hiv 1 central polypurine tract influence on foamy viral vectors to transduce dividing and growth arrested cells |
| url | http://dx.doi.org/10.1155/2014/487969 |
| work_keys_str_mv | AT sergeyshityakov evaluationandpredictionofthehiv1centralpolypurinetractinfluenceonfoamyviralvectorstotransducedividingandgrowtharrestedcells AT carolaforster evaluationandpredictionofthehiv1centralpolypurinetractinfluenceonfoamyviralvectorstotransducedividingandgrowtharrestedcells AT axelrethwilm evaluationandpredictionofthehiv1centralpolypurinetractinfluenceonfoamyviralvectorstotransducedividingandgrowtharrestedcells AT thomasdandekar evaluationandpredictionofthehiv1centralpolypurinetractinfluenceonfoamyviralvectorstotransducedividingandgrowtharrestedcells |