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 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 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 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 Perspectives in Structural Biology written by M. Vijayan and published by Universities Press. This book was released on 1999 with total page 828 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prof. G.N. Ramachandran Has Been Among The Foremost Biophysicists And Structural Biologists Of Our Times, And The Most Outstanding Scientist To Have Worked In Independent India. His Contributions Pertaining To Collagen, Methods Of Structural Analysis, Computer Modelling And Conformational Analysis, And Three-Dimensional Image Reconstruction Have Had A High Global Impact. This Volume In Honour Of Gnr Consists Of Articles At The Cutting Edge Of Structural Biology Contributed By Leading Scientists, Including Two Noble Laureates. It Is Intended To Be A Window To Modern Structural Biology And A Showcase Of The Indian Effort In This Area.
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 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 A Novel Gene Therapy Approach Based on Secreted Antiviral Proteins for the Control of HIV Replication written by Alexander Falkenhagen and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: HIV entry into target cells requires the interaction of the HIV envelope glycoprotein (Env) with a primary receptor (CD4) and a co-receptor (most commonly CCR5 or CXCR4). Protein-based HIV entry inhibitors are highly effective in protecting cells from infection. However, their clinical application is limited because their use requires the frequent injection of highly purified proteins. This study focuses on the development of a gene therapy strategy for the delivery of protein-based HIV entry inhibitors. In Chapter 2 we show that an antibody fragment targeting CCR5 (sscFvPRO140) is secreted from gene-modified human cells and can protect unmodified cells from infection. Chapter 3 describes the secretion and antiviral effect of entry inhibitors targeting HIV Env. A soluble receptor (sCD4), sCD4 covalently linked to a fusion inhibitor (sCD4-FIT45) and sCD4 linked to an antibody fragment targeting the co-receptor-binding site (sCD4-scFv17b) were secreted in significant quantities and protected primary HIV target cells from infection. In Chapter 4 we examine the secretion of sCD4 in a mouse model of HIV infection. sCD4 was present in the blood (~100 ng/ml) of mice engrafted with gene-modified hematopoietic stem cells, reduced viral load over time and protected CD4+ T cells from depletion. Chapter 5 describes the use of gene-modified cell lines for the production of secreted human proteins and their small-scale purification from the culture media. In Chapter 6 we further investigate the antiviral potency of sCD4-FIT45. The bifunctional protein inhibited HIV Env-mediated cell fusion and HIV entry of several primary isolates more potently than VRC01, sCD4, or sCD4-scFv17b. Taken together, we have shown that human cells can be engineered to secrete HIV inhibitors. Furthermore, our results highlight the benefit of combining inhibitors that target receptor-binding and membrane fusion.
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 HIV 1 Immune Escape and Neutralizing Antibodies written by and published by . This book was released on 2002 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The HIV-1 envelope glycoproteins gp120 and gp41 mediate binding and fusion of the virus to target cells. The envelope glycoproteins are exposed on the surface of the virus as trimeric spikes and are the major targets for neutralizing antibodies. The design of envelope glycoprotein-based subunit vaccines has been frustrated by many viral immune escape mechanisms. Trimeric envelope glycoprotein formulations hold promise to overcome limitations of monomeric envelope glycoproteins as immunogens. The generation of native, trimeric envelope glycoprotein complexes, however, remains a major challenge. Here, solid-phase proteoliposomes containing native, trimeric HIV-1 envelope glycoprotein complexes that mimic the trimeric complex as it is found on the viral surface have been designed. In a comparative immunogenicity study, these proteoliposomes were shown to better elicit broadly neutralizing antibodies than gp120. A second trimeric envelope glycoprotein formulation, soluble YU2 gp140-GCN4 constructs, were also shown to better elicit broadly neutralizing antibodies in rabbits, extending a previous study in mice. These data support the hypothesis that trimeric envelope glycoprotein formulations are an advance over gp120-based immunogens. To date, only four broadly neutralizing antibodies against the HIV-1 envelope glycoproteins have been identified. Here, three novel Fab antibody fragments binding to the CD4 binding site of gp120 have been identified from phage-displayed antibody libraries with proteoliposomes. These Fab antibodies display some breadth and potency in neutralizing HIV-1. Comparison of the neutralizing activity of Fab antibodies and whole antibodies directed to the CD4 binding site suggests that these Fab antibodies may significantly gain neutralizing potency as whole antibodies. Many HIV-1 immune escape mechanisms complicate the elicitation of broadly neutralizing antibodies. Core gp120 envelope glycoproteins derived from primary isolate viruses were found t.
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 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 Fluorescence Correlation Spectroscopy written by R. Rigler and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 503 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the first book-length treatment of both the theoretical background to fluorescence correlation spectroscopy (FCS) and a variety of applications in various fields of science. The high spatial and temporal resolution of FCS has made it a powerful tool for the analysis of molecular interactions and kinetics, transport properties due to thermal motion, and flow. It contains an essential contribution from Nobel Prize winner M. Eigen, who is credited with inventing FCS.
Download or read book Current Protocols in Immunology written by John E. Coligan and published by Current Protocols. This book was released on 1991 with total page 846 pages. Available in PDF, EPUB and Kindle. Book excerpt: Current Protocols in Immunology is a three-volume looseleaf manual that provides comprehensive coverage of immunological methods from classic to the most cutting edge, including antibody detection and preparation, assays for functional activities of mouse and human cells involved in immune responses, assays for cytokines and their receptors, isolation and analysis of proteins and peptides, biochemistry of cell activation, molecular immunology, and animal models of autoimmune and inflammatory diseases. Carefully edited, step-by-step protocols replete with material lists, expert commentaries, and safety and troubleshooting tips ensure that you can duplicate the experimental results in your own laboratory. Bimonthly updates, which are filed into the looseleaf, keep the set current with the latest developments in immunology methods. The initial purchase includes one year of updates and then subscribers may renew their annual subscriptions. Current Protocols publishes a family of laboratory manuals for bioscientists, including Molecular Biology, Human Genetics, Protein Science, Cytometry, Cell Biology, Neuroscience, Pharmacology, and Toxicology.
Download or read book Viral Molecular Machines written by Michael G. Rossmann and published by Springer Science & Business Media. This book was released on 2012-02-02 with total page 685 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will contain a series of solicited chapters that concern with the molecular machines required by viruses to perform various essential functions of virus life cycle. The first three chapters (Introduction, Molecular Machines and Virus Architecture) introduce the reader to the best known molecular machines and to the structure of viruses. The remainder of the book will examine in detail various stages of the viral life cycle. Beginning with the viral entry into a host cell, the book takes the reader through replication of the genome, synthesis and assembly of viral structural components, genome packaging and maturation into an infectious virion. Each chapter will describe the components of the respective machine in molecular or atomic detail, genetic and biochemical analyses, and mechanism. Topics are carefully selected so that the reader is exposed to systems where there is a substantial infusion of new knowledge in recent years, which greatly elevated the fundamental mechanistic understanding of the respective molecular machine. The authors will be encouraged to simplify the detailed knowledge to basic concepts, include provocative new ideas, as well as design colorful graphics, thus making the cutting-edge information accessible to broad audience.
Download or read book Disease Control Priorities Third Edition Volume 6 written by King K. Holmes and published by World Bank Publications. This book was released on 2017-11-06 with total page 1027 pages. Available in PDF, EPUB and Kindle. Book excerpt: Infectious diseases are the leading cause of death globally, particularly among children and young adults. The spread of new pathogens and the threat of antimicrobial resistance pose particular challenges in combating these diseases. Major Infectious Diseases identifies feasible, cost-effective packages of interventions and strategies across delivery platforms to prevent and treat HIV/AIDS, other sexually transmitted infections, tuberculosis, malaria, adult febrile illness, viral hepatitis, and neglected tropical diseases. The volume emphasizes the need to effectively address emerging antimicrobial resistance, strengthen health systems, and increase access to care. The attainable goals are to reduce incidence, develop innovative approaches, and optimize existing tools in resource-constrained settings.
