Exploring the potential of group II introns to inactivate human immunodeficiency virus type 1.
This study examined whether insertion of a mobile group II intron into infectious human immunodeficiency virus type 1 (HIV-1) provirus DNA could inhibit virus replication. Introns targeted against two sites within the integrase-coding region were used. The intron-inserted HIV-1 provirus DNA clones were isolated and tested for virus replication. Similar amounts of HIV-1 RNA, Gag protein and progeny virus were produced from HIV-1 provirus DNA and intron-inserted HIV-1 provirus DNA. However, when the progeny virus was tested for its infectivity, although the group II intron-inserted HIV-1 RNA was packaged and reverse-transcribed, the dsDNA failed to integrate, as expected in the absence of a functional integrase, and virus replication was aborted. These results demonstrate that group II introns can confer 'complete' inhibition of HIV-1 replication at the intended step and should be further exploited for HIV-1 gene therapy and other targeted genetic repairs.
Nazari
Reza
R
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3E2, Canada.
Joshi
Sadhna
S
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E2, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3E2, Canada.
D002460:Cell Line; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007438:Introns / Q000235:genetics*; D011533:Proviruses / Q000235:genetics; D014162:Transfection; D038301:Virus Inactivation; D014779:Virus Replication
D004279:DNA, Viral