Selective killing of human immunodeficiency virus-infected cells by targeted gene transfer and inducible gene expression using a recombinant human immunodeficiency virus vector

Citation
K. Miyake et al., Selective killing of human immunodeficiency virus-infected cells by targeted gene transfer and inducible gene expression using a recombinant human immunodeficiency virus vector, HUM GENE TH, 12(3), 2001, pp. 227-233
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN GENE THERAPY
ISSN journal
1043-0342 → ACNP
Volume
12
Issue
3
Year of publication
2001
Pages
227 - 233
Database
ISI
SICI code
1043-0342(20010210)12:3<227:SKOHIV>2.0.ZU;2-L
Abstract
A human immunodeficiency virus type I (HIV-1)-based retroviral vector pseud otyped with HIV envelope containing the herpes simplex virus-thymidine kina se (HSV-TK) gene under the control of the HIV LTR promoter (pHXTKN) was con structed and stably transferred into human CD4(+) H9, CEM, and U937 cells. RNase protection assays did not initially detect expression of the HSV-TK g ene in HXTKN-transduced CD4(+) cells (HXTKN/CD4), but expression was then e fficiently induced by infection with HIV-1, MTT assays showed that after HI V-1 infection, the susceptibility of HXTKN/CD4 cells to ganciclovir (GCV) w as 1000-fold higher than prior to infection, This enabled HIV-1-infected ce lls to be selectively killed by transduction with HXTKN followed by exposur e to GCV, Because the HSV-TK gene is specifically transferred into HIV-1-pe rmissive cells and expressed only after HIV-1 infection, the frequency of u nwanted cell death should be low. Elimination of the HIV-1-infected cells e ffectively inhibited further spread of infectious virus. In addition, the i ntegrated HIV vector sequences were repackaged on infection with HIV-1 and transferred to surrounding untransduced cells. These results are indicative of the potential benefits of using HIV vectors in gene therapies for the t reatment of HIV-1 infection.