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Exploring the potential of group II introns to inactivate human immunodeficiency virus type 1

¹ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3E2, Canada
² Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E2, Canada

Correspondence
Sadhna Joshi
sadhna.joshi.sukhwal{at}utoronto.ca

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.