Residual expression of reporter genes in constructs mimicking HIV genome organization.
Plasmids were constructed whereby the expression of a reporter gene, either the cDNA corresponding to the secreted form of human alkaline phosphatase (SEAP) or the herpes simplex virus type 1 (HSV1) thymidine kinase (tk) gene, was rendered dependent upon the expression of the human immunodeficiency virus type 1 (HIV1) tat and rev proteins. The SEAP or tk genes were placed between HIV1 splice donor and acceptor sites. One SEAP construct carried a series of alternating splice donor and acceptor sites. In all cases, the rev response element mapped within an intron. Despite such mimicry of the HIV1 genome, residual expression of the reporter gene in the absence of tat and rev was observed. These results, as well as non-specific T-cell recruitment, suggest limits to the specificity of using HIV-activated toxic gene expression to kill HIV-infected cells.
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy / Q000821:virology; D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000235:genetics; D015696:Gene Products, tat / Q000235:genetics; D017930:Genes, Reporter; D015316:Genetic Therapy; D005822:Genetic Vectors; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger; D013601:T-Lymphocytes / Q000821:virology; D013937:Thymidine Kinase / Q000235:genetics; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D015694:Gene Products, rev; D015696:Gene Products, tat; D012333:RNA, Messenger; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D013937:Thymidine Kinase; D000469:Alkaline Phosphatase