title: Evaluation and prediction of the HIV-1 central polypurine tract influence on foamy viral vectors to transduce dividing and growth-arrested cells.
abstract: 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.
authors.affiliation: Department of Anesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany.
authors.forename: Sergey
authors.initials: S
authors.lastname: Shityakov
authors.affiliation: Department of Anesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Förster
authors.affiliation: Department of Virology, University of Würzburg, 97074 Würzburg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Rethwilm
authors.affiliation: Department of Bioinformatics, University of Würzburg, 97074 Würzburg, Germany.
authors.forename: Thomas
authors.identifier: 0000-0003-1886-7625
authors.initials: T
authors.lastname: Dandekar
mesh_terms: D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D005544:Forecasting; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics*; D006131:Growth Inhibitors / Q000008:administration & dosage*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D053150:Simian foamy virus / Q000235:genetics*
chemical_list: D006131:Growth Inhibitors