Download or read book Targeting the CD4 and Coreceptor Binding Sites of the HIV 1 Envelope Glycoprotein written by Matthew Ryan Gardner and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The HIV-1 envelope glycoprotein, Env, facilitates the translocation of the viral capsid across the cellular membrane. Env is a trimer of hetero-dimers composed of a gp120 subunit and gp41 transmembrane protein. The gp120 subunit binds the primary receptor, CD4, leading to conformational changes of Env that then promote binding to the coreceptor, principally CCR5 or CXCR4. As the sole protein on the surface of the virion, Env is under continuous pressure from the host's antibody response. Two classes of antibodies target the highly conserved receptor-binding sites of gp120: CD4-binding site (CD4bs) and CD4-induced (CD4i) antibodies.
Download or read book The HIV 1 Envelope Glycoproteins written by Rogier Willem Sanders and published by Amsterdam University Press. This book was released on 2003-12-01 with total page 342 pages. Available in PDF, EPUB and Kindle. Book excerpt: The need for a vaccine against HIV is obvious, but the development of an effective vaccine has met with frustrations. The HIV envelope glycoproteins, residing in the viral membrane, are the sole viral proteins exposed on the outside of virus particles and.
Download or read book Encyclopedia of AIDS written by Thomas J. Hope and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Diverse Specificity and Effector Function Among Human Antibodies to HIV 1 Envelope Glycoprotein Epitopes Exposed by CD4 Binding written by and published by . This book was released on 2012 with total page 10 pages. Available in PDF, EPUB and Kindle. Book excerpt: The HIV-1 envelope glycoprotein (Env) undergoes conformational transitions consequent to CD4 binding and coreceptor engagement during viral entry. The physical steps in this process are becoming defined, but less is known about their significance as targets of antibodies potentially protective against HIV-1 infection. Here we probe the functional significance of transitional epitope exposure by characterizing 41 human mAbs specific for epitopes exposed on trimeric Env after CD4 engagement. These mAbs recognize three epitope clusters: cluster A, the gp120 face occluded by gp41 in trimeric Env; cluster B, a region proximal to the coreceptor-binding site (CoRBS) and involving the V1/V2 domain; and cluster C, the coreceptor-binding site. The mAbs were evaluated functionally by antibody-dependent, cell-mediated cytotoxicity (ADCC) and for neutralization of Tiers 1 and 2 pseudoviruses. All three clusters included mAbs mediating ADCC. However, there was a strong potency bias for cluster A, which harbors at least three potent ADCC epitopes whose cognate mAbs have electropositive paratopes. Cluster A epitopes are functional ADCC targets during viral entry in an assay format using virion-sensitized target cells. In contrast, only cluster C contained epitopes that were recognized by neutralizing mAbs. There was significant diversity in breadth and potency that correlated with epitope fine specificity. In contrast, ADCC potency had no relationship with neutralization potency or breadth for any epitope cluster. In conclusion, Fc-mediated effector function and neutralization coselect with specificity in anti-Env antibody responses, but the nature of selection is distinct for these two antiviral activities.
Download or read book NMR of Proteins and Nucleic Acids written by Kurt Wüthrich and published by Wiley-Interscience. This book was released on 1986 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lists of tables. The foundations: structure and NMR of biopolymers. Resonance assignments and structure determination in proteins. Resonance assignments and structure determiantion in nucleic acids. With NMR to biopolymer conformation and beyond.
Download or read book Lipid Domains written by and published by Academic Press. This book was released on 2015-06-08 with total page 393 pages. Available in PDF, EPUB and Kindle. Book excerpt: Current Topics in Membranes is targeted toward scientists and researchers in biochemistry and molecular and cellular biology, providing the necessary membrane research to assist them in discovering the current state of a particular field and in learning where that field is heading. This volume offers an up to date presentation of current knowledge in the field of Lipid Domains. Written by leading experts Contains original material, both textual and illustrative, that should become a very relevant reference material The material is presented in a very comprehensive manner Both researchers in the field and general readers should find relevant and up-to-date information
Download or read book Dissecting the Complex Mechanisms Behind the Combinatorial Activities of HIV 1 Entry Inhibitors written by Koree Wee Ahn and published by . This book was released on 2017 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: For HIV-1 surface glycoprotein Envelope (Env) to mediate the viral entry process, it must interact with two receptors on the target cell, CD4 and coreceptor (CoR). These receptors trigger a series of conformational changes that result in the fusion of viral and target cell membranes. How receptor binding triggers these conformational changes is not fully understood. While there are three binding sites for each receptor in an Env trimer, neither the minimal receptor binding requirement for entry, nor the role of multivalent binding is known. To address these gaps in knowledge, we examined the combinatorial activity of three classes of HIV-1 entry inhibitors. The first two classes are CD4 (CD4A) and CoR antagonists (CoRA). These antagonists bind the cellular receptors and occlude them from Env. The third class, fusion inhibitors (FI), binds an intermediate conformation of Env during entry and stops membrane fusion. As FI bind a transient intermediate conformation, potency is dependent on the kinetics of entry. In our first project we examined CoRA and FI combinations. Previous studies have shown that these inhibitors are synergistic with one another and attributed synergy to CoRAs slowing the kinetics of entry. However, other studies have reported only additivity. By dissecting the synergistic process using a variety of FIs and mutant Env, we were able to determine that synergy can be lost through two factors, the affinity of FI, and the stoichiometry of CoR binding. These results explain the discrepancies observed in the literature, provide new understanding of the role of CoR binding stoichiometry in entry, and have implications for the combinatorial use of these inhibitors in the clinic. In a second study, we probed the coupling of CD4 and CoR binding by investigating the combinatorial activity of CD4A and CoRA. Unexpectedly, we observed that these two inhibitors were antagonistic with another. However, the combinatorial activity was highly HIV-1 strain dependent. by comparing the combinatorial activity of these inhibitors across multiple HIV-1 strains and dissecting the mechanism of antagonism, we determined that CD4 and CoR binding can drive competing processes in during HIV-1 entry.
Download or read book Advances in Molecular Retrovirology written by Shailendra K. Saxena and published by . This book was released on 2016 with total page 202 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book gives a comprehensive overview of recent advances in Retrovirology, as well as general concepts of molecular biology of retroviral infections, immunopathology, diagnosis, and prevention, to current clinical recommendations in management of retroviruses, including endogenous retroviruses, highlighting the ongoing issues, recent advances, with future directions in diagnostic approaches and therapeutic strategies.
Download or read book Viral Fusion Mechanisms written by Joseph Bentz and published by CRC Press. This book was released on 1992-11-30 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Fusion Mechanisms presents the first comprehensive review on this exciting topic. The book focuses on molecular mechanisms rather than phenomonology and examines a wide range of viruses, including influenza, HIV, Sendai, SFV, Vaccinia, VSV, and RSV. Recent theoretical work on dissecting protein-mediated membrane fusion is discussed, and the most promising new technologies for elucidating mechanisms are highlighted. Viral Fusion Mechanisms is an essential reference for biophysicists, cell biologists, colloid chemists, immunologists, microbiologists, molecular biologists, and virologists.
Download or read book Microbiology in Clinical Practice written by D. C. Shanson and published by Butterworth-Heinemann. This book was released on 2014-06-28 with total page 680 pages. Available in PDF, EPUB and Kindle. Book excerpt: Microbiology in Clinical Practice presents the infections and syndromes caused by micro-organisms. It discusses the management of infective diseases and aetiological agents. It addresses the latex agglutination, immunofluorescent, monoclonal antibody, and nucleic acid probe investigations. Some of the topics covered in the book are the classification and pathogenicity of microbes; classification of bacteria; classification of viruses; classification of fungi; general principles of antimicrobial chemotherapy; antibiotic sensitivity tests; procedures in the laboratory for microbiological diagnosis; and the mode of action of antimicrobial drugs. The resistance to antimicrobial drugs are covered. The microbiological investigations of septicaemia are discussed. The text describes the human immunodeficiency virus infection and AIDS in infants. A study of the congenital immunodeficiency and impaired resistance to infection is presented. A chapter is devoted to the predisposing factors for anaerobic infections. Another section focuses on the infections of the central nervous system. The book can provide useful information to doctors, pathologists, neurologists, students, and researchers.
Download or read book HIV 1 Latency written by Guido Silvestri and published by Springer. This book was released on 2018-10-11 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume summarizes recent advances in understanding the mechanisms of HIV-1 latency, in characterizing residual viral reservoirs, and in developing targeted interventions to reduce HIV-1 persistence during antiretroviral therapy. Specific chapters address the molecular mechanisms that govern and regulate HIV-1 transcription and latency; assays and technical approaches to quantify viral reservoirs in humans and animal models; the complex interchange between viral reservoirs and the host immune system; computational strategies to model viral reservoir dynamics; and the development of therapeutic approaches that target viral reservoir cells. With contributions from an interdisciplinary group of investigators that cover a broad spectrum of subjects, from molecular virology to proof-of-principle clinical trials, this book is a valuable resource for basic scientists, translational investigators, infectious-disease physicians, individuals living with HIV/AIDS and the general public.
Download or read book Mast Cells and Basophils written by Gianni Marone and published by Academic Press. This book was released on 2000-05-25 with total page 738 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mast Cells and Basophils will be essential reading for immunologists, biochemists and medical researchers. Detailed chapters cover all aspects of mast cell and basophil research, from cell development, proteases, histamine, cysteinyl leukotrienes, physiology and pathology to the role of these cells in health and disease. Chapters also discuss the clinical implications of histamine receptor antagonists.
Download or read book Current Perspectives in HIV Infection written by Shailendra K. Saxena and published by BoD – Books on Demand. This book was released on 2013-04-10 with total page 484 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book gives a comprehensive overview of HIV and AIDS including NeuroAIDS, as well as general concepts of pathology, immunity and immunopathology, diagnosis, treatment, epidemiology and etiology to current clinical recommendations in management of HIV/AIDS including NeuroAIDS, highlighting the ongoing issues, recent advances and future directions in diagnostic approaches and therapeutic strategies.
Download or read book The Mapping and Characterization of a Novel Binding Site on HIV 1 Gp120 for the Broadly Neutralizing Monoclonal Antibody IgG1 B12 written by Jillian Waruk and published by . This book was released on 2011 with total page 578 pages. Available in PDF, EPUB and Kindle. Book excerpt: HIV infects target cells via fusion events following surface envelope glycoprotein binding to the CD4 receptor and a chemokine co-receptor. Despite the high sequence variability of envelope across and within HIV-1 subtypes, this process requires conserved sequences and structures on gp120, which also represent good targets for HIV-1 neutralizing antibodies. Few examples of HIV-1 broadly neutralizing antibodies exist, but these antibodies may hold the key to a protective HIV-1 vaccine. One such antibody, IgG1 b12 (b12), binds the CD4 binding site on the HIV-1 envelope glycoprotein gp120. To date, no vaccine preparations have been able to elicit a b12-like response. A complete understanding of the mechanism of b12 binding to gp120 is essential to successful design of an b12-like immune response. Until now, strategies to map the b12 binding site on gp120 have utilized indirect techniques and/or core gp120 and have shown that b12 binds to a site on gp120 that overlaps the CD4 binding site. To more directly map the b12 epitope on intact gp120, epitope excision mass spectrometry mapping was carried out in the MALDI QqTOF platform. The putative epitope sequence was confirmed by tandem mass spectrometry sequencing. Epitope mapping revealed a novel binding site for IgG1 b12 at the gp120 amino terminus called Nterm. b12 bound a synthesized peptide of the epitope and the nature of the epitope was explored by ELISA. Although the Nterm epitope is involved in b12-gp120 interactions, ELISAs also show that the epitope does not make up the entire binding site on gp120. Rabbits immunized with a peptide version of the Nterm epitope do express antibodies that bind monomeric gp120, but these antibody responses do not neutralize HIV-1 in vitro. These data indicate that the b12 binding site on gp120 is much more complex than previously thought. The b12 binds the Nterm sequence of gp120, perhaps in conjunction with the CD4 binding site. It has been shown that another HIV-1-neutralizing antibody, 4E10, also binds this novel Nterm epitope, and this may indicate a similar mechanism of action utilized by these two different antibodies. Though not able to elicit neutralizing antibodies on its own, this epitope may be an important element of the neutralizing b12 epitope and an important component of HIV-1 neutralizing antibody responses.
Download or read book Privileged Scaffolds in Medicinal Chemistry written by Stefan Bräse and published by Royal Society of Chemistry. This book was released on 2015-11-20 with total page 486 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book addresses the various classes of privileged scaffolds and covers the history of their discovery and use.
Download or read book X PLOR written by Axel T. Brünger and published by Yale University Press. This book was released on 1992-01-01 with total page 404 pages. Available in PDF, EPUB and Kindle. Book excerpt: X-PLOR is a highly sophisticated computer program that provides an interface between theoretical foundations and experimental data in structural biology, with specific emphasis on X-ray crystallography and nuclear magnetic resonance spectroscopy in solution of large biological macro-molecules. This manual to X-PLOR Version 3.1 presents the theoretical background, syntax, and function of the program and also provides a comprehensive list of references and sample input files with comments. It is intended primarily for researchers and students in the fields of computational chemistry, structural biology, and computational molecular biology.
Download or read book Human Virology written by John Sidney Oxford and published by Oxford University Press. This book was released on 2016 with total page 365 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by leading authors in the field with both clinical and molecular expertise, Human Virology provides an accessible introduction to this fascinating and important field, making the text ideal for students encountering virology for the first time.
