Combining mutations in HIV-1 reverse transcriptase with mutations in the HIV-1 polypurine tract affects RNase H cleavages involved in PPT utilization

Mary Jane McWilliams, John G. Julias, Stefan G. Sarafianos, W. Gregory Alvord, Eddy Arnold, Stephen H. Hughes

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The RNase H cleavages that generate and remove the polypurine tract (PPT) primer during retroviral reverse transcription must be specific to generate linear viral DNAs that are suitable substrates for the viral integrase. To determine if specific contacts between reverse transcriptase (RT) and the PPT are a critical factor in determining the cleavage specificity of RNase H, we made HIV-1 viruses containing mutations in RT and the PPT at the locations of critical contacts between the protein and the nucleic acid. The effects on titer and RNase H cleavage suggest that combining mutations in RT with mutations in the PPT affect the structure of the protein of the RT/nucleic acid complex in ways that affect the specificity and the rate of PPT cleavage. In contrast, the mutations in the PPT (alone) and RT (alone) affect the specificity of PPT cleavage but have much less effect on the overall rate of cleavage.

Original languageEnglish (US)
Pages (from-to)378-388
Number of pages11
JournalVirology
Volume348
Issue number2
DOIs
StatePublished - May 10 2006

All Science Journal Classification (ASJC) codes

  • Virology

Keywords

  • HIV-1 reverse transcriptase
  • Polypurine tract
  • RNase H cleavage specificity

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