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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/content/journal/jgv/10.1099/vir.0.2008/004333-0
2008-10-01
2021-01-27
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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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