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Inhibition of HIV-1 by a lentiviral vector with a novel tat-inducible expression system and a specific tropism to the target cells

Farazmandfar, T. and Haghshenas, M.R. and Shahbazi, M. (2015) Inhibition of HIV-1 by a lentiviral vector with a novel tat-inducible expression system and a specific tropism to the target cells. Human Gene Therapy, 26 (10). pp. 680-687.

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Abstract

Today, lentiviral vectors are favorable vectors for RNA interference delivery in anti-HIV therapeutic approaches. Nevertheless, problems such as the specific recognition of target cells and uncontrolled expression of the transgene can restrict their use in vivo. Herein we present a new HIV-inducible promoter to express anti-HIV short hairpin RNA (shRNA) by RNA Pol II in mammalian cells. We likewise showed a novel third-generation lentiviral vector system with more safety and a specific tropism to the target cells. The new promoter, CkRhsp, was constructed from the chicken β-actin core promoter with the R region of HIV-1 long terminal repeat fused upstream of minimal hsp70 promoter. This system was induced by HIV-1 Tat, and activates transcription of two shRNAs against two conserved regions of HIV-1 transcripts produced in two steps of the virus life cycle. We also mimicked HIV-1 cell tropism by using the HIV-1 envelope in structure of third-generation lentiviral vector. The new fusion promoter efficiently expressed shRNA in a Tat-inducible manner. HIV-1 replication was inhibited in transient transfection and stable transduction assays. The new viral vector infected only CD4+cells. CkRhsp promoter may be safer than other inducible promoters for shRNA-mediated gene therapies against HIV. The use of the wild envelope in the vector packaging system may provide the specific targeting T lymphocytes and hematopoietic stem cells for anti-HIV-1 therapeutic approaches in vivo. © Mary Ann Liebert, Inc. 2015.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: CkRhsp short hairpin RNA; Gag protein; heat shock protein 70; lentivirus vector; short hairpin RNA; transactivator protein; unclassified drug, antiviral activity; Article; cell viability; controlled study; gene expression; gene expression system; human; human cell; Human immunodeficiency virus 1; in vitro study; long terminal repeat; nonhuman; promoter region; transcription initiation site; transient expression; transient transfection; tropism; viral gene delivery system; viral tropism; virus inhibition; virus replication
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 10 Sep 2016 05:46
Last Modified: 16 Jan 2017 05:11
URI: http://eprints.goums.ac.ir/id/eprint/4720

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