HIV-1-based defective lentiviral vectors efficiently transduce human monocytes-derived macrophages and suppress replication of wild-type HIV-1

Zeng, Lingbing; Planelles, Vicente; Sui, Ziye; Gartner, Suzanne; Maggirwar, Sanjay B.; Dewhurst, Stephen; Ye, Linbai; Nerurkar, Vivek R.; Yanagihara, Richard; Lu, Yuanan

doi:10.1002/jgm.825

Cited by 21 publications

(22 citation statements)

References 55 publications

(61 reference statements)

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“…Overall, these data suggest that the efficiency of DLV-mediated gene transduction in mouse monocytes may be influenced by the extent of cellular differentiation and/or by other changes associated with prolonged in vitro culture. This is consistent with similar observations using primary human monocytes/macrophage cell cultures (Neil et al, 2001;Zeng et al, 2005).…”

Section: Prolonged Time In Culture Results In More Efficient Gene Trasupporting

confidence: 93%

“…It has recently been demonstrated that primary monocyte cultures isolated from human blood can be efficiently transduced in vitro with HIV-based viral vector pseudotyped with VSV-G envelope and transduced cells maintained an active and long-term reporter gene expression (Zeng et al, 2005). To further investigate the use of the genetically modified monocytes/ macrophages in gene therapy for the central nervous system, it is of importance to establish an experimental model system to test the efficacy of monocyte trafficking into the brain and the efficiency of target gene expression in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…All vector viruses were pseudotyped with the vesicular stomatitis virus (VSV) G protein. The HIV-based vector used in this study is a recently constructed vector containing no structural genes (gag/pol/ env) and accessory genes (Zeng et al, 2005). The FIV-based Felix vector plasmids were generously provided by Dr. G.P.…”

Section: Vector Productionmentioning

confidence: 99%

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Effective transduction of primary mouse blood- and bone marrow-derived monocytes/macrophages by HIV-based defective lentiviral vectors

Zeng

Yang

et al. 2006

Journal of Virological Methods

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Human immunodeficiency virus type 1-based defective lentiviral vectors (HIV-based vector) efficiently transduce a wide range of mammalian cell types, but little is known with respect to their utility for gene transfer applications involving primary mouse monocytes/macrophages. This may be important for preclinical development of a range of potential gene therapeutic modalities. Present study described the development of an optimized method for viral vector-mediated gene transfer into primary mouse monocytes/macrophages and the establishment of reproducible protocols for cell isolation/cultivation. It has been determined that bone marrow-derived monocytes/macrophages were consistently more susceptible to viral vector-mediated gene transduction, as compared to bloodderived cells. It has also been documented that the efficiency of transduction increased when cells were maintained in vitro, prior to exposure to vector virus. Finally, experiments were conducted to compare the efficiency of gene transfer mediated by HIV-based vectors to that achieved by other lentivirus or retrovirus vector systems. These studies showed that HIV-based vector system was consistently superior. Overall, these results establish a new and efficient method for gene transfer into primary mouse monocytes/macrophages. This may be of utility in the preclinical development of gene therapies that target this important cell type.

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Section: Prolonged Time In Culture Results In More Efficient Gene Trasupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Effective transduction of primary mouse blood- and bone marrow-derived monocytes/macrophages by HIV-based defective lentiviral vectors

Zeng

Yang

et al. 2006

Journal of Virological Methods

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“…HIV-based lentivirus stocks were generated by transient plasmid transfection into 293T cells as described previously 19). PRx1 cDNA was amplified using 5'-CGCGAATTCATGTCTTCAGGAAATGCA-3' and 5'-CGCCTCGAGTCACTTCTGCTTAGAGAA-3' using Taq polymerase.…”

Section: Methodsmentioning

confidence: 99%

Protective Effects of Peroxiredoxin on Hydrogen Peroxide Induced Oxidative Stress and Apoptosis in Cardiomyocytes

Park

Kim

et al. 2012

Korean Circ J

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Background and ObjectivesThe redox system is an important anti-oxidative system composed of thioredoxin, thioredoxin reductase, and peroxiredoxin (PRx). The fine details of PRx expression and its protective effects in various cells in cardiovascular tissue under oxidative stress created by hydrogen peroxide have not been fully elucidated.Subjects and MethodsOxidative stress was induced by adding hydrogen peroxide at 0.25 mM for 2 hours to rat neonatal cardiomyocytes (rCMCs), rat vascular smooth muscle cells (rVSMCs), and human umbilical vein endothelial cells (HUVECs). Apoptosis was quantified by flow cytometry and the expression patterns of the six PRx isoforms were evaluated by western blotting in the three cell lines after hydrogen peroxide stimulation. Apoptosis and the cell survival signal pathway were evaluated by PRx1 gene delivery using lentiviral vector in hydrogen peroxide stimulated rCMCs versus green fluorescence protein gene delivery.ResultsHydrogen peroxide induced 25% apoptosis in rCMCs. Furthermore, the PRx1 and 5 isoforms were found to be overexpressed in hydrogen peroxide treated rCMCs, and PRx1 overexpression by gene delivery was found to reduce hydrogen peroxide induced rCMCs apoptosis significantly. In addition, this effect was found to originate from cell survival pathway modification.ConclusionHydrogen peroxide induced significant oxidative stress in rCMCs, rVSMCs, and HUVECs, and PRx1 overexpression using a lentiviral vector system significantly reduced hydrogen peroxide induced rCMCs apoptosis by upregulation of cell survival signals and downregulation of apoptotic signals. These findings suggest that PRx1 could be used as a treatment strategy for myocardial salvage in conditions of oxidative stress.

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“…Scientists are already overcoming the problems of insufficient gene transduction by using novel constructs [49] or by switching to lentiviral-mediated transduction [50,51]. The first clinical trial using lentiviral vectors in HIV-positive patients began in 2001, and results will be forthcoming [52].…”

Section: Resultsmentioning

confidence: 99%

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Marathe

Wooley

2007

Genet Vaccines Ther

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Despite advances and options available in gene therapy for HIV-1 infection, its application in the clinical setting has been challenging. Although published data from HIV-1 clinical trials show safety and proof of principle for gene therapy, positive clinical outcomes for infected patients have yet to be demonstrated. The cause for this slow progress may arise from the fact that HIV is a complex multi-organ system infection. There is uncertainty regarding the types of cells to target by gene therapy and there are issues regarding insufficient transduction of cells and long-term expression. This paper discusses state-of-the-art molecular approaches against HIV-1 and the application of these treatments in current and ongoing clinical trials.

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HIV-1-based defective lentiviral vectors efficiently transduce human monocytes-derived macrophages and suppress replication of wild-type HIV-1

Cited by 21 publications

References 55 publications

Effective transduction of primary mouse blood- and bone marrow-derived monocytes/macrophages by HIV-based defective lentiviral vectors

Effective transduction of primary mouse blood- and bone marrow-derived monocytes/macrophages by HIV-based defective lentiviral vectors

Protective Effects of Peroxiredoxin on Hydrogen Peroxide Induced Oxidative Stress and Apoptosis in Cardiomyocytes

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