The development and testing of retroviral vectors expressing trans-dominant mutants of HIV-1 proteins to confer anti-HIV-1 resistance.
Trans-dominant mutants of human immunodeficiency virus type 1 (HIV-1) Tat and Rev are attractive candidates for use in gene therapy in the treatment of HIV-1 infections because both are essential for viral replication. Retroviral vectors were constructed to allow either Tat-inducible or Tat- and Rev-inducible expression of trans-dominant mutants of Tat and Rev. These vectors were used to infect a human CD4+ lymphocyte-derived cell line, MT4. To determine the efficacy of various Tat and Rev mutants in inhibiting HIV-1 multiplication, MT4 cells containing mutant-expressing constructs were infected with HIV-1, and the amount of HIV-1 released in the culture medium was measured for up to 30 days. A high level of resistance was observed in cells expressing the double tat/rev mutant in a Tat-inducible manner.
Liem
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University of Toronto, Department of Microbiology, Ontario, Canada.
Ramezani
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A
Li
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Joshi
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015694:Gene Products, rev / Q000235:genetics*; D015696:Gene Products, tat / Q000235:genetics*; D005799:Genes, Dominant; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D015658:HIV Infections / Q000628:therapy; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D013601:T-Lymphocytes / Q000382:microbiology; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D015696:Gene Products, tat; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus