1887

Abstract

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.

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2008-10-01
2020-01-28
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References

  1. Adachi, A., Gendelman, H. E., Koenig, S., Folks, T., Willey, R., Rabson, A. & Martin, M. A. ( 1986; ). Production of acquired immunodeficiency virus-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol 59, 284–291.
    [Google Scholar]
  2. Guo, H., Karberg, M., Long, M., Jones, J. P., III, Sullenger, B. & Lambowitz, A. M. ( 2000; ). Group II introns designed to insert into therapeutically relevant DNA target sites in human cells. Science 289, 452–457.[CrossRef]
    [Google Scholar]
  3. Jones, J. P., III, Kierlin, M. N., Coon, R. G., Perutka, J., Lambowitz, A. M. & Sullenger, B. A. ( 2005; ). Retargeting mobile group II introns to repair mutant genes. Mol Ther 11, 687–694.[CrossRef]
    [Google Scholar]
  4. Joshi, S., Van Brunschot, A., Robson, I. & Bernstein, A. ( 1990; ). Efficient replication, integration, and packaging of retroviral vectors with modified LTRs containing the packaging signal. Nucleic Acids Res 18, 4223–4226.[CrossRef]
    [Google Scholar]
  5. Liem, S. E., Ramezani, A., Li, X. & Joshi, S. ( 1993; ). The development and testing of retroviral vectors expressing trans-dominant mutants of HIV-1 proteins to confer anti-HIV-1 resistance. Hum Gene Ther 4, 625–634.[CrossRef]
    [Google Scholar]
  6. Magli, M. C., Dick, J. E., Huszar, D., Bernstein, A. & Phillips, R. A. ( 1987; ). Modulation of gene expression in multiple hematopoietic cell lineages following retroviral vector gene transfer. Proc Natl Acad Sci U S A 84, 789–793.[CrossRef]
    [Google Scholar]
  7. Menendez-Arias, L. ( 2002; ). Molecular basis of fidelity of DNA synthesis and nucleotide specificity of retroviral reverse transcriptases. Prog Nucleic Acid Res Mol Biol 71, 91–147.
    [Google Scholar]
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