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Evaluation and Prediction of the HIV-1 Central Polypurine Tract Influence on Foamy Viral Vectors to Transduce Dividing and Growth-Arrested Cells

Please always quote using this URN: urn:nbn:de:bvb:20-opus-112763
  • 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 activityRetroviral 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.show moreshow less

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Metadaten
Author: Sergey Shityakov, Carola Förster, Axel Rethwilm, Thomas Dandekar
URN:urn:nbn:de:bvb:20-opus-112763
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Virologie und Immunbiologie
Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004)
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Year of Completion:2014
Source:The Scientific World Journal Vol. 2014 (2014), Article ID 487969, 11 p., http://dx.doi.org/10.1155/2014/487969
DOI:https://doi.org/10.1155/2014/487969
Sonstige beteiligte Institutionen:Interdisziplinäres Zentrum für Klinische Forschung (ZIKF), Würzburg
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Evaluation; Prognose; HIV; Spumaviren; Einfluss
Release Date:2015/05/12
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2014
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung