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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.

HIV (Viruses) --- Reverse transcriptase --- RNA-Directed DNA Polymerase --- DNA-Directed DNA Polymerase --- DNA Nucleotidyltransferases --- Nucleotidyltransferases --- Phosphotransferases --- Transferases --- Enzymes --- Enzymes and Coenzymes --- Chemicals and Drugs --- HIV Reverse Transcriptase --- Biology --- Health & Biological Sciences --- Microbiology & Immunology --- Immunology. --- HIV infections --- Research --- Methodology. --- HIV (Viruses) infections --- HTLV-III infections --- HTLV-III-LAV infections --- Human T-lymphotropic virus III infections --- Immunobiology --- Medicine. --- Virology. --- Infectious diseases. --- Biomedicine. --- Infectious Diseases. --- Life sciences --- Serology --- Lentivirus infections --- Sexually transmitted diseases --- Medical virology. --- Emerging infectious diseases. --- Medical microbiology --- Virology --- Virus diseases --- Emerging infections --- New infectious diseases --- Re-emerging infectious diseases --- Reemerging infectious diseases --- Communicable diseases --- Microbiology

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Currently, there is no single source that permits comparison of the factors, elements, enzymes and/or mechanisms employed by different classes of viruses for genome replication. As a result, we (and our students) often restrict our focus to our particular system, missing out on the opportunity to define unifying themes in viral genome replication or benefit from the advances in other systems. For example, extraordinary biological and experimental paradigms that have been established over the past five years for the DNA replication systems of bacteriophage T4 and T7 will likely be of great value to anyone interested in studying a replisome from any virus. These studies could easily go unnoticed by animal RNA and DNA virologists. It is our hope that this monograph will cross-fertilize and invigorate the field, as well as encourage students into this area of research.

Viral genomes. --- Viruses --Reproduction. --- Viral genomes --- Viruses --- Virus Replication --- Genetics --- Genome, Viral --- Virus Physiological Processes --- Biology --- Genome --- Microbiological Processes --- Virus Physiological Phenomena --- Biological Science Disciplines --- Genetic Structures --- Microbiological Phenomena --- Genetic Phenomena --- Natural Science Disciplines --- Disciplines and Occupations --- Phenomena and Processes --- Microbiology & Immunology --- Health & Biological Sciences --- Reproduction --- Reproduction. --- Replication of viruses --- Viral replication --- Viral genome --- Virus genomes --- Medicine. --- Human genetics. --- Immunology. --- Virology. --- Biochemistry. --- Cell biology. --- Microbiology. --- Biomedicine. --- Cell Biology. --- Biochemistry, general. --- Human Genetics. --- Microbial genomes --- Medical virology. --- Cytology. --- Heredity, Human --- Human biology --- Physical anthropology --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Chemistry --- Medical sciences --- Cell biology --- Cellular biology --- Cells --- Cytologists --- Immunobiology --- Life sciences --- Serology --- Microbial biology --- Microorganisms --- Medical microbiology --- Virology --- Virus diseases --- Composition --- Microbiology

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This is a comprehensive tool covering all manifestations of antimicrobial resistance, with viral, bacterial, parasitical and fungal resistance each given a dedicated section. The underlining molecular mechanisms, which depend not only on the microbe, but on the specific drug (target), are highly diverse, and are covered in great detail. This work also discusses and compares the biological, biochemical and structural aspects of resistance and its evolution.

Immunology. Immunopathology --- Pharmacology. Therapy --- Medical microbiology, virology, parasitology --- immunologie --- medische microbiologie --- resistentie (farmacologie) --- geneesmiddelentolerantie --- virologie

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This is a comprehensive tool covering all manifestations of antimicrobial resistance, with viral, bacterial, parasitical and fungal resistance each given a dedicated section. The underlining molecular mechanisms, which depend not only on the microbe, but on the specific drug (target), are highly diverse, and are covered in great detail. This work also discusses and compares the biological, biochemical and structural aspects of resistance and its evolution.

Drug resistance. --- Medical microbiology. --- Immunology. --- Virology. --- Drug Resistance. --- Medical Microbiology. --- Anti-infective agents --- Drug resistance in microorganisms