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

Overview

Journal ScientificWorldJournal

Publisher Wiley

Specialty Biology

Date 2014 Jul 11

PMID 25009830

Citations 1

Authors

Sergey Shityakov

Carola Forster

Axel Rethwilm

Thomas Dandekar

Affiliations

Soon will be listed here.

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.

Citing Articles

The fourth central polypurine tract guides the synthesis of prototype foamy virus plus-strand DNA.

Chen D, Song J, Sun Y, Li Z, Wen D, Liu Q Virus Genes. 2017; 53(2):259-265.

PMID: 28185138 DOI: 10.1007/s11262-016-1425-8.

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