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https://www.readbyqxmd.com/read/27908641/free-energy-perturbation-calculation-of-relative-binding-free-energy-between-broadly-neutralizing-antibodies-and-the-gp120-glycoprotein-of-hiv-1
#1
Anthony J Clark, Tatyana Gindin, Baoshan Zhang, Lingle Wang, Robert Abel, Colleen S Murret, Fang Xu, Amy Bao, Nina J Lu, Tongqing Zhou, Peter D Kwong, Lawrence Shapiro, Barry Honig, Richard A Friesner
Direct calculation of relative binding affinities between antibodies and antigens is a long-sought goal. However, despite substantial efforts, no generally applicable computational method has been described. Here we describe a systematic free energy perturbation (FEP) protocol and calculate the binding affinities between the gp120 envelope glycoprotein of HIV-1 and three broadly neutralizing antibodies (bNAbs) of the VRC01 class. The protocol has been adapted from successful studies of small molecules to address the challenges associated with modeling protein-protein interactions...
November 28, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27893822/deciphering-multiplicity-of-hiv-1c-infection-transmission-of-closely-related-multiple-viral-lineages
#2
Vlad Novitsky, Sikhulile Moyo, Rui Wang, Simani Gaseitsiwe, M Essex
BACKGROUND: A single viral variant is transmitted in the majority of HIV infections. However, about 20% of heterosexually transmitted HIV infections are caused by multiple viral variants. Detection of transmitted HIV variants is not trivial, as it involves analysis of multiple viral sequences representing intra-host HIV-1 quasispecies. METHODOLOGY: We distinguish two types of multiple virus transmission in HIV infection: (1) HIV transmission from the same source, and (2) transmission from different sources...
2016: PloS One
https://www.readbyqxmd.com/read/27888531/fate-of-microglia-during-hiv-1-infection-from-activation-to-senescence
#3
REVIEW
Natalie C Chen, Andrea T Partridge, Christian Sell, Claudio Torres, Julio Martín-García
Microglia support productive human immunodeficiency virus type 1 (HIV-1) infection and disturbed microglial function could contribute to the development of HIV-associated neurocognitive disorders (HAND). Better understanding of how HIV-1 infection and viral protein exposure modulate microglial function during the course of infection could lead to the identification of novel therapeutic targets for both the eradication of HIV-1 reservoir and treatment of neurocognitive deficits. This review first describes microglial origins and function in the normal central nervous system (CNS), and the changes that occur during aging...
November 26, 2016: Glia
https://www.readbyqxmd.com/read/27888114/limonene-reduces-hyperalgesia-induced-by-gp120-and-cytokines-by-modulation-of-il-1-%C3%AE-and-protein-expression-in-spinal-cord-of-mice
#4
Ana Claudia Piccinelli, Priscila Neder Morato, Marcelo Dos Santos Barbosa, Julio Croda, Jared Sampson, Xiangpeng Kong, Elisabete Castelon Konkiewitza, Edward B Ziff, Jaime Amaya-Farfan, Cândida Aparecida Leite Kassuya
AIMS: We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. MAIN METHODS: Male Swiss mice received gp120, IL-1β or TNF-α intrathecally or sterile saline as a control. A mechanicalsensitivity test was performed at 2 and 3h after the injection. Spinal cord and blood samples were isolated for protein quantification. KEY FINDINGS: Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3h after the injections...
November 22, 2016: Life Sciences
https://www.readbyqxmd.com/read/27881646/activation-and-inactivation-of-primary-human-immunodeficiency-virus-hiv-1-envelope-glycoprotein-trimers-by-cd4-mimetic-compounds
#5
Navid Madani, Amy M Princiotto, Connie Zhao, Fatemeh Jahanbakhshsefidi, Max Mertens, Alon Herschhorn, Bruno Melillo, Amos B Smith, Joseph Sodroski
: Human immunodeficiency virus (HIV-1) entry into cells is mediated by the viral envelope glycoproteins (Env), a trimer of three gp120 exterior glycoproteins and three gp41 transmembrane glycoproteins. The metastable Env is triggered to undergo entry-related conformational changes when gp120 binds sequentially to the receptors, CD4 and CCR5, on the target cell. Small-molecule CD4-mimetic compounds (CD4mc) bind gp120 and act as competitive inhibitors of gp120-CD4 engagement. Some CD4mc have been shown to trigger Env prematurely, initially activating Env function, followed by rapid and irreversible inactivation...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27879316/structure-based-design-of-cyclically-permuted-hiv-1-gp120-trimers-that-elicit-neutralizing-antibodies
#6
Sannula Kesavardhana, Raksha Das, Michael Citron, Rohini Datta, Linda Ecto, Nonavinakere Seetharam Srilatha, Daniel DiStefano, Ryan Swoyer, Joseph G Joyce, Somnath Dutta, Celia C LaBranche, David C Montefiori, Jessica A Flynn, Raghavan Varadarajan
A major goal for HIV-1 vaccine development is an ability to elicit strong and durable broadly neutralizing antibody (bNAb) responses. The trimeric envelope glycoprotein (Env) spikes on HIV-1 are known to contain multiple epitopes that are susceptible to bNAbs isolated from infected individuals. Nonetheless, all trimeric and monomeric Env immunogens designed to date have failed to elicit such antibodies. We report the structure guided design of HIV-1 cyclically permuted gp120 that forms homogeneous, stable trimers and displays enhanced binding to multiple bNAbs, including VRC01, VRC03, VRC-PG04, PGT128 and the quaternary epitope-specific bNAbs PGT145 and PGDM1400...
November 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27872270/hiv-glycoprotein-gp120-impairs-fast-axonal-transport-by-activating-tak1-signaling-pathways
#7
Sarah H Berth, Nichole Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria Sapar, Gerardo Morfini, Scott T Brady
Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment...
December 2016: ASN Neuro
https://www.readbyqxmd.com/read/27871328/membrane-bound-modified-form-of-clade-b-env-jrcsf-is-suitable-for-immunogen-design-as-it-is-efficiently-cleaved-and-displays-all-the-broadly-neutralizing-epitopes-including-v2-and-c2-domain-dependent-conformational-epitopes
#8
Supratik Das, Saikat Boliar, Nivedita Mitra, Sweety Samal, Manish Bansal, Wayne C Koff, Bimal K Chakrabarti
BACKGROUND: Antigenicity of HIV-1 envelope proteins (Envs) of both lab-adapted and primary isolates expressed on the cell surface rarely match with in vitro neutralization of viruses, pseudo-typed with corresponding Envs. Often, both neutralizing and non-neutralizing antibodies bind to Envs expressed on the cell membrane. This could be due to the lack of efficient cleavage of Env expressed on the cell surface. Naturally occurring, efficiently cleaved Envs with appropriate antigenic properties are relatively rare...
November 21, 2016: Retrovirology
https://www.readbyqxmd.com/read/27869200/classification-of-tandem-mass-spectra-for-identification-of-n-and-o-linked-glycopeptides
#9
Shadi Toghi Eshghi, Weiming Yang, Yingwei Hu, Punit Shah, Shisheng Sun, Xingde Li, Hui Zhang
Analysis of intact glycopeptides by mass spectrometry is essential to determining the microheterogeneity of protein glycosylation. Higher-energy collisional dissociation (HCD) fragmentation of glycopeptides generates mono- or disaccharide ions called oxonium ions that carry information about the structure of the fragmented glycans. Here, we investigated the link between glycan structures and the intensity of oxonium ions in the spectra of glycopeptides and utilized this information to improve the identification of glycopeptides in biological samples...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27863502/annexin-a2-antibodies-but-not-inhibitors-of-the-annexin-a2-heterotetramer-impair-productive-hiv-1-infection-of-macrophages-in-vitro
#10
Andrew W Woodham, Adriana M Sanna, Julia R Taylor, Joseph G Skeate, Diane M Da Silva, Lodewijk V Dekker, W Martin Kast
During sexual transmission of human immunodeficiency virus (HIV), macrophages are initial targets for HIV infection. Secretory leukocyte protease inhibitor (SLPI) has been shown to protect against HIV infection of macrophages through interactions with annexin A2 (A2), which is found on the macrophage cell surface as a heterotetramer (A2t) consisting of A2 and S100A10. Therefore, we investigated potential protein-protein interactions between A2 and HIV-1 gp120 through a series of co-immunoprecipitation assays and a single molecule pulldown (SiMPull) technique...
November 18, 2016: Virology Journal
https://www.readbyqxmd.com/read/27853317/high-mannose-specific-lectin-msl-mediates-key-interactions-of-the-vaginal-lactobacillus-plantarum-isolate-cmpg5300
#11
Shweta Malik, Mariya I Petrova, Nicole C E Imholz, Tine L A Verhoeven, Sam Noppen, Els J M Van Damme, Sandra Liekens, Jan Balzarini, Dominique Schols, Jos Vanderleyden, Sarah Lebeer
To characterize the interaction potential of the human vaginal isolate Lactobacillus plantarum CMPG5300, its genome was mined for genes encoding lectin-like proteins. cmpg5300.05_29 was identified as the gene encoding a putative mannose-binding lectin. Phenotypic analysis of a gene knock-out mutant of cmpg5300.05_29 showed that expression of this gene is important for auto-aggregation, adhesion to the vaginal epithelial cells, biofilm formation and binding to mannosylated glycans. Purification of the predicted lectin domain of Cmpg5300...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27851829/diversification-in-the-hiv-1-envelope-hyper-variable-domains-v2-v4-and-v5-and-higher-probability-of-transmitted-founder-envelope-glycosylation-favor-the-development-of-heterologous-neutralization-breadth
#12
S Abigail Smith, Samantha L Burton, William Kilembe, Shabir Lakhi, Etienne Karita, Matt Price, Susan Allen, Eric Hunter, Cynthia A Derdeyn
A recent study of plasma neutralization breadth in HIV-1 infected individuals at nine International AIDS Vaccine Initiative (IAVI) sites reported that viral load, HLA-A*03 genotype, and subtype C infection were strongly associated with the development of neutralization breadth. Here, we refine the findings of that study by analyzing the impact of the transmitted/founder (T/F) envelope (Env), early Env diversification, and autologous neutralization on the development of plasma neutralization breadth in 21 participants identified during recent infection at two of those sites: Kigali, Rwanda (n = 9) and Lusaka, Zambia (n = 12)...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27843002/comparison-of-the-patterns-of-antibody-recall-responses-to-hiv-1-gp120-and-hepatitis-b-surface-antigen-in-immunized-mice
#13
Hao-Tong Yu, Jia-Ye Wang, Dan Tian, Ming-Xia Wang, Yan Li, Li Yuan, Wen-Jiang Chen, Di Li, Min Zhuang, Hong Ling
To date, we still lack an ideal strategy for designing envelope glycoprotein (Env) vaccines to elicit potent protective antibodies against HIV-1 infection. Since the human hepatitis B virus surface antigen (HBsAg) is representative of effective vaccines that can induce ideal humoral immune responses, knowledge of how it elicits antibody responses and T helper cells would be an useful reference for HIV vaccine development. We compared the characteristics of the HIV-1 Env gp120 trimer and HBsAg in antibody elicitation and induction of T follicular helper (Tfh) and memory B cells in immunized Balb/c mice...
December 7, 2016: Vaccine
https://www.readbyqxmd.com/read/27835615/modulation-of-innate-and-adaptive-cellular-immunity-relevant-to-hiv-1-vaccine-design-by-seminal-plasma
#14
Kevin J Selva, Stephen J Kent, Matthew S Parsons
OBJECTIVES: Mucosal exposure to HIV-1 infection generally occurs in the presence of semen. Immunomodulation by seminal plasma (SP) is well described in the reproductive biology literature. Little is known, however, about the impact of SP on innate and adaptive anti-HIV-1 cellular immunity. DESIGN: This study investigated the effects of SP on immune responses considered important for prophylactic HIV-1 vaccine development, namely innate and adaptive cellular immunity mediated by NK cells and T-cells, respectively...
November 9, 2016: AIDS
https://www.readbyqxmd.com/read/27822141/hiv-1-nef-promotes-migration-and-chemokine-synthesis-of-human-basophils-and-mast-cells-through-the-interaction-with-cxcr4
#15
Francesca Wanda Rossi, Nella Prevete, Felice Rivellese, Antonio Lobasso, Filomena Napolitano, Francescopaolo Granata, Carmine Selleri, Amato de Paulis
BACKGROUND: The Nef protein can be detected in plasma of HIV-1-infected patients and plays a role in the pathogenesis of HIV-1. Nef produced during the early stages of infection is fundamental in creating the ideal environment for viral replication, e.g. by reducing the ability of infected cells to induce an immune response. AIM: Based on previous experience showing that both Tat and gp41 of HIV-1 are potent chemotactic factors for basophils and mast cells, and gp120 is a powerful stimulus for the release of histamine and cytokines (IL-4 and IL-13) from basophils, in this study we aimed to verify if the HIV Nef protein can exert some effects on basophils and mast cells purified from healthy volunteers through the interaction with the CXCL12 receptor, CXCR4...
2016: Clinical and Molecular Allergy: CMA
https://www.readbyqxmd.com/read/27815444/an-hiv-1-env-antibody-complex-focuses-antibody-responses-to-conserved-neutralizing-epitopes
#16
Yajing Chen, Richard Wilson, Sijy O'Dell, Javier Guenaga, Yu Feng, Karen Tran, Chi-I Chiang, Heather E Arendt, Joanne DeStefano, John R Mascola, Richard T Wyatt, Yuxing Li
Elicitation of broadly neutralizing Ab (bNAb) responses to the conserved elements of the HIV-1 envelope glycoproteins (Env), including the primary receptor CD4 binding site (CD4bs), is a major focus of vaccine development yet to be accomplished. However, a large number of CD4bs-directed bNAbs have been isolated from HIV-1-infected individuals. Comparison of the routes of binding used by the CD4bs-directed bNAbs from patients and the vaccine-elicited CD4bs-directed mAbs indicates that the latter fail to neutralize primary virus isolates because they approach the Env spike with a vertical angle and contact the specific surface residues occluded in the native spike, including the bridging sheet on gp120...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27809912/frequency-and-env-determinants-of-hiv-1-subtype-c-strains-from-antiretroviral-therapy-naive-subjects-that-display-incomplete-inhibition-by-maraviroc
#17
Katharina Borm, Martin R Jakobsen, Kieran Cashin, Jacqueline K Flynn, Paula Ellenberg, Lars Ostergaard, Benhur Lee, Melissa J Churchill, Michael Roche, Paul R Gorry
BACKGROUND: Entry of human immunodeficiency virus type 1 (HIV-1) into cells involves the interaction of the viral gp120 envelope glycoproteins (Env) with cellular CD4 and a secondary coreceptor, which is typically one of the chemokine receptors CCR5 or CXCR4. CCR5-using (R5) HIV-1 strains that display reduced sensitivity to CCR5 antagonists can use antagonist-bound CCR5 for entry. In this study, we investigated whether naturally occurring gp120 alterations in HIV-1 subtype C (C-HIV) variants exist in antiretroviral therapy (ART)-naïve subjects that may influence their sensitivity to the CCR5 antagonist maraviroc (MVC)...
November 3, 2016: Retrovirology
https://www.readbyqxmd.com/read/27808126/recombinant-production-of-influenza-hemagglutinin-and-hiv-1-gp120-antigenic-peptides-using-a-cleavable-self-aggregating-tag
#18
Wanghui Xu, Qing Zhao, Lei Xing, Zhanglin Lin
The increasing demand for antigenic peptides in the development of novel serologic diagnostics and epitope-based vaccines requires rapid and reliable peptide synthesis techniques. Here we investigated a method for efficient recombinant expression and purification of medium- to large-sized antigenic peptides in E. coli. Previously we devised a streamlined protein expression and purification scheme based on a cleavable self-aggregating tag (cSAT), which comprised an intein molecule and a self-aggregating peptide ELK16...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807235/molecular-architecture-of-the-cleavage-dependent-mannose-patch-on-a-soluble-hiv-1-envelope-glycoprotein-trimer
#19
Anna-Janina Behrens, David J Harvey, Emilia Milne, Albert Cupo, Abhinav Kumar, Nicole Zitzmann, Weston B Struwe, John P Moore, Max Crispin
: The formation of a correctly folded and natively glycosylated HIV-1 viral spike is dependent on protease cleavage of the gp160 precursor protein in the Golgi apparatus. Cleavage induces a compact structure, which not only renders the spike capable of fusion but also limits further maturation of its extensive glycosylation. The redirection of the glycosylation pathway to preserve underprocessed oligomannose-type glycans is an important feature in immunogen design as glycans contribute to or influence the epitopes of numerous broadly neutralizing antibodies...
November 2, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27799557/cryo-em-structure-of-a-cd4-bound-open-hiv-1-envelope-trimer-reveals-structural-rearrangements-of-the-gp120-v1v2-loop
#20
Haoqing Wang, Alexander A Cohen, Rachel P Galimidi, Harry B Gristick, Grant J Jensen, Pamela J Bjorkman
The HIV-1 envelope (Env) glycoprotein, a trimer of gp120-gp41 heterodimers, relies on conformational flexibility to function in fusing the viral and host membranes. Fusion is achieved after gp120 binds to CD4, the HIV-1 receptor, and a coreceptor, capturing an open conformational state in which the fusion machinery on gp41 gains access to the target cell membrane. In the well-characterized closed Env conformation, the gp120 V1V2 loops interact at the apex of the Env trimer. Less is known about the structure of the open CD4-bound state, in which the V1V2 loops must rearrange and separate to allow access to the coreceptor binding site...
October 31, 2016: Proceedings of the National Academy of Sciences of the United States of America
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