Inhibition of human immunodeficiency virus type 1 multiplication by antisense and sense RNA expression.
Human immunodeficiency virus type 1 (HIV-1) primarily infects CD4+ lymphocytes and macrophages and causes AIDS in humans. Retroviral vectors allowing neomycin phosphotransferase (npt) gene expression were engineered to express 5' sequences of HIV-1 RNA in the antisense or sense orientation and used to transform the human CD4+ lymphocyte-derived MT4 cell line. Cells expressing antisense or sense RNA to the HIV-1 tat mRNA leader sequence, as part of the 3' untranslated region of the npt mRNA, remained sensitive to HIV-1 infection. In contrast, resistance to HIV-1 infection was observed in cells expressing antisense RNA to the HIV-1 primer-binding site or to the region 5' to the primer-binding site as part of the 3' region of the npt mRNA. Cells expressing the tat mRNA leader sequence in the sense orientation as a precise replacement of the 5' untranslated region of npt mRNA were also resistant to HIV-1. These results indicate that sense and antisense approaches can be used to interfere with HIV-1 multiplication.
Joshi
S
S
Department of Microbiology, University of Toronto, Ontario, Canada.
Van Brunschot
A
A
Asad
S
S
van der Elst
I
I
Read
S E
SE
Bernstein
A
A
D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002472:Cell Transformation, Viral; D015870:Gene Expression; D005814:Genes, Viral; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids; D016372:RNA, Antisense / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D015183:Restriction Mapping; D014779:Virus Replication / Q000235:genetics*
D015345:Oligonucleotide Probes; D016372:RNA, Antisense; D012367:RNA, Viral