Download or read book The Role of Lysyl tRNA Synthetase in Selective Packaging of TRNAlys3 Into HIV 1 written by Mohammad Hassan Javanbakht Rezai and published by . This book was released on 2003 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: "LysRS is carried into the viruses by its interaction with Gag. We have mapped the sites of interaction between HIV-1 Gag and LysRS using in vivo and in vitro techniques. We find that Gag sequences within the C-terminal domain of CA which contains the CA dimerization site, interact with LysRS sequences which include motif 1, which contains the LysRS dimerization site." --
Download or read book The Role of Lysyl tRNA Synthetase in Selective Packaging of TRNALys3 Into HIV 1 microform written by Mohammad Hassan Javanbakht Rezai and published by Library and Archives Canada = Bibliothèque et Archives Canada. This book was released on 2003 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Critical Role of Phosphorylated Human Lysyl tRNA Synthetase in the HIV 1 Lifecycle written by Yingke Tang (Ph. D. in chemistry) and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Host cell tRNALys3 is selectively incorporated into HIV-1 particles and acts as the primer to initiate reverse transcription of the viral genome. Lysyl-tRNA synthetase (LysRS), the only cellular factor that specifically interacts with all tRNALys isoacceptors, is also incorporated into HIV-1 particles through interaction with HIV-1 Gag. LysRS facilitates selective incorporation of tRNALys into viral particles, a process that is important for progeny virion infectivity. A recent study reported the unexpected finding that LysRS is partially re-localized from its normal cytoplasmic location in the multi-synthetase complex (MSC) to the nucleus during HIV-1 infection. Here, we investigated the nuclear function of LysRS in HIV-1 replication. Both nuclear localization and packaging of LysRS into HIV-1 particles depend on phosphorylation of S207(pS207). This modification results in a LysRS conformational change, loss of aminoacylation activity, and release from the MSC. Using a pS207-specific antibody, we detected endogenous pS207-LysRS during single-cycle HIV-1 infection in HEK 293T, Jurkat, SupT-1 and THP-1 cell lines. Previous work showed that pS207-LysRS regulates transcription in mast cells via increased synthesis of diadenosine tetraphosphate, Ap4A, which leads to USF-2 and MITF transcription factor activation. We now show that LysRS phosphorylation also regulates HIV-1 transcription in CD4+ T cell lines. Overexpression of wild-type LysRS, but not the phosphoablative S207A mutant, activated HIV-1 LTR promoter-driven luciferase expression. We also generated a homozygous LysRS-S207A knock-in Jurkat cell line (JurkatS207A) using CRISPR-cas9. HIV-1NL4-3 replication is severely reduced in JurkatS207A, an effect that is rescued by S207D-LysRS expression, supporting a critical role for LysRS phosphorylation in the HIV-1 lifecycle. In the MSC, LysRS interacts with the N-terminal domain (N36) of the aminoacyl-tRNA synthetase–interacting multifunctional protein 2 (AIMP2). This interaction locks LysRS into an aminoacylation-competent conformation. We now show that overexpressing the AIMP2-N36 peptide blocks the nuclear relocalization of LysRS and inhibits HIV-1 replication, presumably by binding and sequestering pS207-LysRS in the cytoplasm. Transcription of HIV-1 gRNA and other USF-2 target genes was also lower in JurkatS207A cells as well as in the AIMP2-N36-expressing cells, supporting a regulatory role for LysRS in the nucleus. We showed that transfection of exogenous Ap4A promotes transcription and reactivation of HIV-1 in Jurkat cells. Thus, we propose that nuclear pS207-LysRS generates Ap4A to activate HIV-1 transcription, suggesting possible roles for LysRS in maintaining HIV-1 latency and exposing new potential targets for antiviral intervention. To investigate the effect of LysRS phosphorylation on selective packaging of non-aminoacylated tRNALys3, total viral RNA was analyzed by acidic northern blotting and RT-qPCR. Whereas over 95% of tRNAs in cells are charged, all tRNALys3 incorporated into viral particles, as well as other minor packaged tRNA species, are uncharged. tRNALys3 packaging levels are significantly decreased in LysRS knockdown cells, JurkatS207A cells and AIMP2-N36 expressing cells, supporting a key role for pS207-LysRS in tRNALys3 packaging. In summary, these studies address unanswered questions regarding the critical roles of pS207-LysRS in the HIV-1 lifecycle and provide insights into novel anti-viral strategies. In an ongoing microscopy study, we are employing several imaging methods to investigate the cellular location of tRNALys3 primer annealing. A DNA probe was designed and confirmed to specifically detect annealed tRNALys3 using fluorescence in situ hybridization (FISH). In addition, HIV-1 Gag and gRNA were visualized by immunofluorescence staining and the MS2-GFP coat protein system, respectively. Taken together, this study will reveal the cellular location of tRNALys3 annealing to the HIV-1 PBS during assembly. Recent in vitro studies identified a high-affinity DNA aptamer that bound HIV-1 reverse transcriptase (RT) with low picomolar affinity. This 38-mer aptamer folds into a hairpin and binds to RT, adopting a pre-bent conformation that mimics the structure of the template-primer complex. To investigate the anti-HIV effect of this aptamer in cells, we used a novel cell penetrating cyclic peptide (Cpp) as the vehicle to deliver the DNA aptamer into HIV-1 producer cells or infected cells. Progeny viral production and viral infectivity were significantly impaired when the producer cells were treated with low nM concentrations of the Cpp/aptamer complex. However, the Cpp/aptamer treatment only resulted in moderate inhibition of incoming HIV-1 infection, consistent with recent reports that capsid uncoating occurs in the nucleus. This study suggests an RT-targeting aptamer delivered using the Cpp approach may be a promising new anti-HIV-1 strategy.
Download or read book The Packaging and Annealing of Primer TRNALys3 in HIV 1 written by Jenan Saadatmand and published by . This book was released on 2008 with total page 436 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of the Interaction Between HIV 1 Gag and Human Lysyl tRNA Synthetase written by Brandie J. Kovaleski and published by . This book was released on 2007 with total page 292 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Progress in Nucleic Acid Research and Molecular Biology written by Kivie Moldave and published by Gulf Professional Publishing. This book was released on 2005-09-20 with total page 414 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nucleic acids are the fundamental building blocks of DNA and RNA and are found in virtually every living cell. Molecular biology is a branch of science that studies the physicochemical properties of molecules in a cell, including nucleic acids, proteins, and enzymes. Increased understanding of nucleic acids and their role in molecular biology will further many of the biological sciences including genetics, biochemistry, and cell biology. Progress in Nucleic Acid Research and Molecular Biology is intended to bring to light the most recent advances in these overlapping disciplines with a timely compilation of reviews comprising each volume.
Download or read book Aminoacyl tRNA Synthetases in Biology and Medicine written by Sunghoon Kim and published by Springer. This book was released on 2014-04-28 with total page 355 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will focus on new molecular interactions and novel activities and the associated diseases that have been recently discovered from the studies of eukaryotic and mammalian aminoacyl-tRNA synthetases. In addition, the potential applications of ARS researches in biotechnology and medicine will be addressed.
Download or read book Viral Genome Replication written by Craig E. Cameron and published by Springer Science & Business Media. This book was released on 2009-05-28 with total page 636 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides the first comprehensive review of viral genome replication strategies, emphasizing not only pathways and regulation but also the structure-function, mechanism, and inhibition of proteins and enzymes required for this process.
Download or read book HIV 1 Molecular Biology and Pathogenesis Viral Mechanisms written by and published by Elsevier. This book was released on 2007-06-13 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume covers the latest advances in the mechanisms of pathogenesis of the HIV-1 virus on target cells. Its companion volume, Advances in Pharmacology 56, shows how new developments in understanding the virus translate to the clinical setting.
Download or read book Human Immunodeficiency Virus Reverse Transcriptase written by Stuart LeGrice and published by Springer Science & Business Media. This book was released on 2013-07-23 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Dissertation Abstracts International written by and published by . This book was released on 2006 with total page 848 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Investigating Nucleic Acid protein and Protein protein Interactions that Govern HIV 1 Replication Using Fluorescence Techniques written by Minh Kim Hong and published by . This book was released on 2004 with total page 356 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Autoimmune Myositis From Immunological to Rheumatological Aspects written by Zhiyong Chen and published by Frontiers Media SA. This book was released on 2022-11-30 with total page 341 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Retrovirus Cell Interactions written by Leslie Parent and published by Academic Press. This book was released on 2018-08-09 with total page 622 pages. Available in PDF, EPUB and Kindle. Book excerpt: Retrovirus-Cell Interactions provides an up-to-date review of the interactions between retroviruses and the cells they infect, offering a comprehensive understanding of how retroviruses hijack cellular factors to facilitate virus replication. Drugs targeting viral enzymes have been developed to treat HIV; the next challenge is to inhibit virus-cell interactions as next generation treatment strategies. Organized according to the retrovirus' replication cycle, this book does not focus exclusively on HIV, but rather includes important findings in other retroviral systems, including animal retroviruses, retrotransposons, and endogenous retroelements to allow broad comparisons on important commonalities and differences. - Provides a valuable starting point for people who want to develop a detailed understanding of retroviral replication - Includes future-thinking strategies, such as next-generation treatment and anti-retroviral therapeutics - Features important commonalities and differences among retroviral systems
Download or read book Encyclopedia of Cell Biology written by and published by Academic Press. This book was released on 2015-08-07 with total page 2972 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Encyclopedia of Cell Biology, Four Volume Set offers a broad overview of cell biology, offering reputable, foundational content for researchers and students across the biological and medical sciences. This important work includes 285 articles from domain experts covering every aspect of cell biology, with fully annotated figures, abundant illustrations, videos, and references for further reading. Each entry is built with a layered approach to the content, providing basic information for those new to the area and more detailed material for the more experienced researcher. With authored contributions by experts in the field, the Encyclopedia of Cell Biology provides a fully cross-referenced, one-stop resource for students, researchers, and teaching faculty across the biological and medical sciences. Fully annotated color images and videos for full comprehension of concepts, with layered content for readers from different levels of experience Includes information on cytokinesis, cell biology, cell mechanics, cytoskeleton dynamics, stem cells, prokaryotic cell biology, RNA biology, aging, cell growth, cell Injury, and more In-depth linking to Academic Press/Elsevier content and additional links to outside websites and resources for further reading A one-stop resource for students, researchers, and teaching faculty across the biological and medical sciences
Download or read book Principles of Virology written by Jane Flint and published by John Wiley & Sons. This book was released on 2020-08-07 with total page 1136 pages. Available in PDF, EPUB and Kindle. Book excerpt: Principles of Virology, the leading virology textbook in use, is an extremely valuable and highly informative presentation of virology at the interface of modern cell biology and immunology. This text utilizes a uniquely rational approach by highlighting common principles and processes across all viruses. Using a set of representative viruses to illustrate the breadth of viral complexity, students are able to understand viral reproduction and pathogenesis and are equipped with the necessary tools for future encounters with new or understudied viruses. This fifth edition was updated to keep pace with the ever-changing field of virology. In addition to the beloved full-color illustrations, video interviews with leading scientists, movies, and links to exciting blogposts on relevant topics, this edition includes study questions and active learning puzzles in each chapter, as well as short descriptions regarding the key messages of references of special interest. Volume I: Molecular Biology focuses on the molecular processes of viral reproduction, from entry through release. Volume II: Pathogenesis and Control addresses the interplay between viruses and their host organisms, on both the micro- and macroscale, including chapters on public health, the immune response, vaccines and other antiviral strategies, viral evolution, and a brand new chapter on the therapeutic uses of viruses. These two volumes can be used for separate courses or together in a single course. Each includes a unique appendix, glossary, and links to internet resources. Principles of Virology, Fifth Edition, is ideal for teaching the strategies by which all viruses reproduce, spread within a host, and are maintained within populations. This edition carefully reflects the results of extensive vetting and feedback received from course instructors and students, making this renowned textbook even more appropriate for undergraduate and graduate courses in virology, microbiology, and infectious diseases.
Download or read book Principles of Virology Volume 1 written by Jane Flint and published by John Wiley & Sons. This book was released on 2020-11-03 with total page 610 pages. Available in PDF, EPUB and Kindle. Book excerpt: Principles of Virology, the leading virology textbook in use, is an extremely valuable and highly informative presentation of virology at the interface of modern cell biology and immunology. This text utilizes a uniquely rational approach by highlighting common principles and processes across all viruses. Using a set of representative viruses to illustrate the breadth of viral complexity, students are able to under-stand viral reproduction and pathogenesis and are equipped with the necessary tools for future encounters with new or understudied viruses. This fifth edition was updated to keep pace with the ever-changing field of virology. In addition to the beloved full-color illustrations, video interviews with leading scientists, movies, and links to exciting blogposts on relevant topics, this edition includes study questions and active learning puzzles in each chapter, as well as short descriptions regarding the key messages of references of special interest. Volume I: Molecular Biology focuses on the molecular processes of viral reproduction, from entry through release. Volume II: Pathogenesis and Control addresses the interplay between viruses and their host organisms, on both the micro- and macroscale, including chapters on public health, the immune response, vaccines and other antiviral strategies, viral evolution, and a brand new chapter on the therapeutic uses of viruses. These two volumes can be used for separate courses or together in a single course. Each includes a unique appendix, glossary, and links to internet resources. Principles of Virology, Fifth Edition, is ideal for teaching the strategies by which all viruses reproduce, spread within a host, and are maintained within populations. This edition carefully reflects the results of extensive vetting and feedback received from course instructors and students, making this renowned textbook even more appropriate for undergraduate and graduate courses in virology, microbiology, and infectious diseases.
