Inhibition of the integrases of human immunodeficiency viruses type 1 and type 2 by reverse transcriptases

Iris Oz, Orna Avidan, Amnon Hizi

Research output: Contribution to journalArticlepeer-review

Abstract

We present evidence that the integrases (INs) of HIV types 1 and 2 are inhibited in vitro by the reverse transcriptases (RTs) of HIV-1, HIV-2 and murine leukaemia virus. Both 3′-end processing and 3′-end joining (strand transfer) activities of IN were affected by the RTs. Full inhibitions were accomplished with most RT and IN combinations tested at around equimolar RT/IN ratios. The disintegration activity of IN was also inhibited by RTs. Neither DNA synthesis nor the ribonuclease H (RNase H) domain of RT were involved in IN inhibition, since specific DNA polymerase inhibitors did not affect the level of IN inhibition, and the p51 isoform of HIV-1 RT (which lacks the RNase H domain) is as effective in inhibiting IN as the heterodimeric p66/p51 isoform. On the other hand, the catalytic activities of HIV RTs were not affected by the INs, showing that RTs can inhibit IN activities, whereas INs do not inhibit RTs. We postulate that sequences and/or three-dimensional protein structures common to RTs interact with INs and inhibit their activities. We show evidence for this hypothesis and discuss the possible sites of IN involved in this interaction.

Original languageEnglish
Pages (from-to)557-566
Number of pages10
JournalBiochemical Journal
Volume361
Issue number3
DOIs
StatePublished - 1 Feb 2002

Keywords

  • HIV
  • Integration
  • Retrovirus
  • Reverse transcription

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