The base excision repair pathway is required for efficient lentivirus integration

Kristine E. Yoder, Amy Espeseth, Xiao hong Wang, Qingming Fang, Maria Teresa Russo, R. Stephen Lloyd, Daria Hazuda, Robert W. Sobol, Richard Fishel

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

An siRNA screen has identified several proteins throughout the base excision repair (BER) pathway of oxidative DNA damage as important for efficient HIV infection. The proteins identified included early repair factors such as the base damage recognition glycosylases OGG1 and MYH and the late repair factor POLß, implicating the entire BER pathway. Murine cells with deletions of the genes Ogg1, Myh, Neil1 and Polß recapitulate the defect of HIV infection in the absence of BER. Defective infection in the absence of BER proteins was also seen with the lentivirus FIV, but not the gammaretrovirus MMLV. BER proteins do not affect HIV infection through its accessory genes nor the central polypurine tract. HIV reverse transcription and nuclear entry appear unaffected by the absence of BER proteins. However, HIV integration to the host chromosome is reduced in the absence of BER proteins. Pre-integration complexes from BER deficient cell lines show reduced integration activity in vitro. Integration activity is restored by addition of recombinant BER protein POLß. Lentiviral infection and integration efficiency appears to depend on the presence of BER proteins.

Original languageEnglish (US)
Article numbere17862
JournalPloS one
Volume6
Issue number3
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yoder, K. E., Espeseth, A., Wang, X. H., Fang, Q., Russo, M. T., Lloyd, R. S., Hazuda, D., Sobol, R. W., & Fishel, R. (2011). The base excision repair pathway is required for efficient lentivirus integration. PloS one, 6(3), [e17862]. https://doi.org/10.1371/journal.pone.0017862