Resistance to human immunodeficiency virus type 1 (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme.
Toward gene therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in AIDS, Moloney murine leukemia virus-derived retroviral vectors were engineered to allow constitutive and tat-inducible expression of an HIV-1 5' leader sequence-specific ribozyme (Rz1). These vectors were used to infect the human CD4+ lymphocyte-derived MT4 cell line. The stable MT4 transformants expressing an HIV-1 RNA-specific ribozyme, under the control of the herpes simplex virus thymidine kinase (tk) promoter, were found to be somewhat resistant to HIV-1 infection as virus production was delayed. In cells allowing ribozyme expression under control of the simian virus 40 or cytomegalovirus promoter, the rate of HIV-1 multiplication was slightly decreased, and virus production was delayed by about 14 days. The highest level of resistance to HIV-1 infection was observed in MT4 cells transformed with a vector containing a fusion tk-TAR (trans activation-responsive) promoter to allow ribozyme expression in a constitutive and tat-inducible manner; no HIV-1 production was observed 22 days after infection of these cells. These results indicate that retroviral vectors expressing HIV-1 RNA-specific ribozymes can be used to confer resistance to HIV-1 infection.
Weerasinghe
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M
Department of Microbiology, University of Toronto, Ontario, Canada.
Liem
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Asad
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Read
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Joshi
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D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D002472:Cell Transformation, Viral; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000276:immunology; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics*; D016337:RNA, Catalytic / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D013997:Time Factors
D015704:CD4 Antigens; D016337:RNA, Catalytic; D012367:RNA, Viral