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Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
13:07

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells

Published on: January 30, 2019

Topoisomerase I dissociates human immunodeficiency virus type 1 reverse transcriptase from genomic RNAs

Hidehiro Takahashi1, Hirofumi Sawa, Hideki Hasegawa

  • 1Department of Pathology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. htakahas@nih.go.jp

Biochemical and Biophysical Research Communications
|January 7, 2004
PubMed

Insights

Human topoisomerase I specifically releases HIV-1 reverse transcriptase from RNA, unlike other proteins. This suggests a key role for topoisomerase I in regulating HIV-1 replication and reverse transcriptase binding.

Area of Science:

  • Molecular Biology
  • Virology
  • Biochemistry

Background:

  • Human topoisomerase I and HIV-1 reverse transcriptase (RT) both bind to structural RNAs.
  • These molecules cooperate in synthesizing complementary DNA (cDNA) during HIV-1 replication.

Purpose of the Study:

  • To investigate the specific interaction between human topoisomerase I and HIV-1 RT binding to RNA.
  • To determine if topoisomerase I can dissociate other RNA-binding proteins or viral RTs.

Main Methods:

  • In vitro binding assays were used to assess the dissociation of HIV-1 RT from RNA by human topoisomerase I.
  • The effect of topoisomerase I on the binding of HIV-1 nucleocapsid proteins and murine leukemia virus RT to RNA was also examined.

Main Results:

  • Human topoisomerase I selectively dissociated HIV-1 RT, which exhibits strong binding to structural RNAs.
  • Topoisomerase I did not dissociate HIV-1 nucleocapsid proteins or murine leukemia virus RT from RNA.
  • This indicates a specific interaction between human topoisomerase I and HIV-1 RT.

Conclusions:

  • Human topoisomerase I plays a specific role in regulating the binding of HIV-1 RT to structural RNAs.
  • Topoisomerase I may be a critical factor in the HIV-1 replication cycle.
  • Targeting this interaction could offer new therapeutic strategies for HIV-1 infection.

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