期刊
JOURNAL OF VIROLOGY
卷 83, 期 19, 页码 9854-9862出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00357-09
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资金
- National Institute of Diabetes, Digestive, and Kidney Diseases
- National Heart, Lung, and Blood Institute of the National Institutes of Health
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZICHL002338, Z01HL006010, Z01HL006008, ZIAHL006008, ZIAHL006010] Funding Source: NIH RePORTER
Human immunodeficiency virus type 1 (HIV-1) vectors transduce rhesus blood cells poorly due to a species-specific block by TRIM5 alpha and APOBEC3G, which target HIV-1 capsid and viral infectivity factor (Vif), respectively. We sought to develop a lentiviral vector capable of transducing both human and rhesus blood cells by combining components of both HIV-1 and simian immunodeficiency virus (SIV), including SIV capsid (sCA) and SIV Vif. A chimeric HIV-1 vector including sCA (chi HIV) was superior to the conventional SIV in transducing a human blood cell line and superior to the conventional HIV-1 vector in transducing a rhesus blood cell line. Among human CD34(+) hematopoietic stem cells (HSCs), the chi HIV and HIV-1 vectors showed similar transduction efficiencies; in rhesus CD34(+) HSCs, the chi HIV vector yielded superior transduction rates. In in vivo competitive repopulation experiments with two rhesus macaques, the chi HIV vector demonstrated superior marking levels over the conventional HIV-1 vector in all blood lineages (first rhesus, 15 to 30% versus 1 to 5%; second rhesus, 7 to 15% versus 0.5 to 2%, respectively) 3 to 7 months postinfusion. In summary, we have developed an HIV-1-based lentiviral vector system that should allow comprehensive preclinical testing of HIV-1-based therapeutic vectors in the rhesus macaque model with eventual clinical application.
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