Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration

  • Amy F. Weil
    Departments of aPharmacology and Molecular Sciences and
  • Devlina Ghosh
    Departments of aPharmacology and Molecular Sciences and
  • Yan Zhou
    Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Lauren Seiple
    Departments of aPharmacology and Molecular Sciences and
  • Moira A. McMahon
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093; and
  • Adam M. Spivak
    Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132
  • Robert F. Siliciano
    Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • James T. Stivers
    Departments of aPharmacology and Molecular Sciences and

書誌事項

公開日
2013-01-22
DOI
  • 10.1073/pnas.1219702110
公開者
Proceedings of the National Academy of Sciences

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説明

<jats:title>Significance</jats:title> <jats:p>Misincorporation of dUTP into DNA is detrimental to eukaryotes, prokaryotes, and viruses. This study reveals the fate of uracilated HIV-1 DNA in human cells. Early stages of the viral life cycle are unaffected, but integration of uracilated viral DNA into the host genome is prevented. This effect is wholly dependent on the presence of UNG2, a nuclear enzyme that excises uracil from DNA. This study establishes that UNG2 is a restriction factor for uracilated HIV-1 DNA and explains why this pathway is not fully engaged in CD4+ T cells and macrophages.</jats:p>

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