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Human Immunodeficiency Virus Reverse Transcriptase

A Bench-to-Bedside Success

  • Stuart LeGrice
  • Matthias Gotte

Table of contents

  1. Front Matter
    Pages i-x
  2. Robert Yarchoan, Hiroaki Mitsuya
    Pages 1-20
  3. Structure and Function of HIV RT

    1. Front Matter
      Pages 21-21
    2. Dorota Piekna-Przybylska, Robert A. Bambara
      Pages 23-51
    3. Marcin Nowotny, Małgorzata Figiel
      Pages 53-75
    4. Stuart F. J. LeGrice
      Pages 77-95
  4. Mechanism of Action of Approved RT Inhibitors

    1. Front Matter
      Pages 97-97
    2. Gaofei Lu, Antonio J. Acosta-Hoyos, Walter A. Scott
      Pages 99-122
    3. Kalyan Das, Eddy Arnold, Stephen H. Hughes
      Pages 123-139
  5. Alternative Strategies to Interfere with the Function of HIV RT

    1. Front Matter
      Pages 141-141
    2. Daouda Abba Moussa, Audrey Agopian, Gilles Divita
      Pages 173-189
    3. Gregory L. Beilhartz, Brian J. Scarth, Matthias Götte
      Pages 191-204
    4. Christopher P. Jones, Karin Musier-Forsyth
      Pages 205-221
  6. HIV Genetic Variability and the Problem of Drug Resistance

    1. Front Matter
      Pages 223-223
    2. John S. Albin, Reuben S. Harris
      Pages 253-280
    3. Gilda Tachedjian, Nicolas Sluis-Cremer
      Pages 281-303
    4. Mary Kearney, John Coffin
      Pages 305-325
  7. Prevention and Future Approaches

    1. Front Matter
      Pages 327-327
    2. Jan Balzarini
      Pages 329-347
  8. Back Matter
    Pages 349-361

About this book

Introduction

The Reverse Transcriptase (RT) of Human Immunodeficiency Virus Type 1 (HIV-1) arguably ranks amongst one of the most extensively studied retroviral enzymes. Heterologous expression and purification of HIV-1 RT in the early eighties, approval of the first nucleoside analogue RT inhibitor (NRTI) in 1987, discovery of resistance to RT inhibitors, approval of the first non-nucleoside analogue RT inhibitor (NNRTI) in 1996 and the various crystal structures of RT with and without bound substrate(s) and/or inhibitors represent only a few of the important milestones that describe the a bench-to-bedside success in the continuing effort to combat HIV-1 infection and its consequences. Nucleoside and nonnucleoside RT inhibitors remain important components in frequently used drug regimens to treat the infection. RT inhibitors also play important roles in recently validated strategies to prevent transmission of the virus. The relevance of HIV-1 RT as a drug target has simultaneously triggered interest in basic research studies aimed at providing a more detailed understanding of interactions between proteins, nucleic acids, and small molecule ligands in general terms. In light of the ever-growing knowledge on structure and function of HIV-1 RT, this enzyme serves as a valuable “model system” in efforts to develop novel experimental tools and to explain biochemical processes. This monograph is designed to provide an overview of important aspects in past and current HIV-1 RT research, with focus on mechanistic aspects and translation of knowledge into drug discovery and development. The first section includes chapters with emphasis placed on the coordination of the RT-associated DNA polymerase and ribonuclease H (RNase H) activities. The second covers mechanisms of action and future perspectives associated with NRTIs and NNRTIs, while the third section includes chapters focusing on novel strategies to target the RT enzyme. Chapters of the final part are intended to discuss mechanisms involved in HIV variability and the development of drug resistance. We hope that these contributions will stimulate interest, and encourage research aimed at the development of novel RT inhibitors. The lack of bona fide RNase H inhibitors with potent antiviral activity provides an example for challenges and opportunities in the field.

Keywords

DNA Synthesis HIV/AIDS Retroviral Therapy Reverse Transcriptase

Editors and affiliations

  • Stuart LeGrice
    • 1
  • Matthias Gotte
    • 2
  1. 1., HIV Drug Resistance ProgramNational Cancer InstituteFrederickUSA
  2. 2.McGill UniversityMontrealCanada

Bibliographic information