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

Author:

Shityakov Sergey1,Förster Carola1,Rethwilm Axel2,Dandekar Thomas3ORCID

Affiliation:

1. Department of Anesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany

2. Department of Virology, University of Würzburg, 97074 Würzburg, Germany

3. Department of Bioinformatics, University of Würzburg, 97074 Würzburg, Germany

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.

Funder

Deutsche Forschungsgemeinschaft

Publisher

Hindawi Limited

Subject

General Environmental Science,General Biochemistry, Genetics and Molecular Biology,General Medicine

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