期刊
JOURNAL OF VIROLOGY
卷 83, 期 16, 页码 8153-8162出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00220-09
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资金
- NIH [R01 AI058862-06, R01 AI058862-04S1]
Current gene transfer protocols for resting CD4(+) T cells include an activation step to enhance transduction efficiency. This step is performed because it is thought that resting cells are resistant to transduction by lentiviral-based gene therapy vectors. However, activating resting cells prior to transduction alters their physiology, with foreseeable and unforeseeable negative consequences. Thus, it would be desirable to transduce resting CD4(+) T cells without activation. We recently demonstrated, contrary to the prevailing belief, that wild-type human immunodeficiency virus (HIV) integrates into resting CD4(+) T cells. Based on that finding, we investigated whether a commonly used, vesicular stomatitis virus glycoprotein G (VSV-G)-pseudotyped lentiviral gene therapy vector could also integrate into resting CD4(+) T cells. To investigate this, we inoculated resting CD4(+) T cells with lentiviral particles that were pseudotyped with VSV-G or CXCR4-tropic HIV Env and assayed binding, fusion, reverse transcription, and integration. We found that the VSV-G-pseudotyped lentiviral vector failed to fuse to resting CD4(+) T cells while HIV Env-pseudotyped lentiviral vectors fused, reverse transcribed, and integrated in resting cells. Our findings suggest that HIV Env could be used effectively for the delivery of therapeutic genes to resting CD4(+) T cells and suggest that fusion may be the critical step restricting transduction of resting CD4(+) T cells by lentiviral gene therapy vectors.
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