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https://www.readbyqxmd.com/read/28446609/glycosylation-of-the-core-of-the-hiv-1-envelope-subunit-protein-gp120-is-not-required-for-native-trimer-formation-or-viral-infectivity
#1
Ujjwal Rathore, Piyali Saha, Sannula Kesavardhana, Aditya Arun Kumar, Rohini Datta, Sivasankar Devanarayanan, Raksha Das, John R Mascola, Raghavan Varadarajan
The gp120 subunit of HIV-1 envelope (Env) protein is heavily glycosylated at approximately 25 glycosylation sites, of which ~7-8 are located in the V1/V2 and V3 variable loops and the others in the remaining core gp120 region. Glycans partially shield Env from recognition by the host immune system and also are believed to be indispensable for proper folding of gp120 and for viral infectivity. Previous attempts to alter glycosylation sites in Env typically involved mutating the glycosylated asparagine residues to structurally similar glutamines or to alanines...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28429756/a-non-canonical-binding-interface-in-the-crystal-structure-of-hiv-1-gp120-core-in-complex-with-cd4
#2
Liang-Wei Duan, Hui Zhang, Meng-Ting Zhao, Ji-Xue Sun, Wen-Li Chen, Jian-Ping Lin, Xin-Qi Liu
Numerous crystal structures of HIV gp120 have been reported, alone or with receptor CD4 and cognate antibodies; however, no sole gp120/CD4 complex without stabilization by an antibody is available. Here, we report a crystal structure of the gp120/CD4 complex without the aid of an antibody from HIV-1 CRF07_BC, a strain circulating in China. Interestingly, in addition to the canonical binding surface, a second interacting interface was identified. A mutagenesis study on critical residues revealed that the stability of this interface is important for the efficiency of Env-mediated membrane fusion...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28425451/ifn%C3%AE-protects-neurons-from-damage-in-a-murine-model-of-hiv-1-associated-brain-injury
#3
Victoria E Thaney, Alan M O'Neill, Melanie M Hoefer, Ricky Maung, Ana B Sanchez, Marcus Kaul
Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28422786/antibody-mediated-immune-exclusion-of-hiv
#4
Ruth M Ruprecht, Samir K Lakhashe
PURPOSE OF REVIEW: Although approximately 90% of all HIV transmissions in humans occur through mucosal contact, the induction of mucosal anti-HIV immune responses has remained understudied. Here we summarize data demonstrating the powerful protection that is achievable at mucosal frontlines through virus-specific mucosal IgA alone or combined with IgG. RECENT FINDINGS: Passive immunization with different monoclonal antibody subclasses but identical epitope specificity (the conserved V3-loop crown of HIV gp120) has revealed that the dimeric IgA1 (dIgA1) form with its open hinge can prevent simian-human immunodeficiency virus (SHIV) acquisition in rhesus macaques at a higher rate than dIgA2...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28404572/an-hiv-envelope-gp120-fc-fusion-protein-elicits-effector-antibody-responses-in-rhesus-macaques
#5
Zhanna Shubin, Weizhong Li, Bhawna Poonia, Guido Ferrari, Celia LaBranche, David Montefiori, Xiaoping Zhu, C David Pauza
A goal for HIV prevention programs is to develop safe and effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 portion of HIV envelope glycoprotein (Env) and seek to improve the quality and quantity of antibodies by altering the sequence, conformation, oligomerization or glycosylation of gp120 to activate appropriate germline B cells and mimic the subsequent maturation pathways seen in infected individuals...
April 12, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28396421/antigenicity-defined-conformations-of-an-extremely-neutralization-resistant-hiv-1-envelope-spike
#6
Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S Seaman, Stephen C Harrison, Andrea Carfi, Bing Chen
The extraordinary genetic diversity of the HIV-1 envelope spike [Env; trimeric (gp160)3, cleaved to (gp120/gp41)3] poses challenges for vaccine development. Envs of different clinical isolates exhibit different sensitivities to antibody-mediated neutralization. Envs of difficult-to-neutralize viruses are thought to be more stable and conformationally homogeneous trimers than those of easy-to-neutralize viruses, thereby providing more effective concealment of conserved, functionally critical sites. In this study we have characterized the antigenic properties of an Env derived from one of the most neutralization-resistant HIV-1 isolates, CH120...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28395728/-preparation-and-characterization-of-monoclonal-antibody-against-gp120-v1-v2-domain-of-hiv-1-subtype-crf01_ae
#7
Ying Chu, Xiangdan Gong, Jianwei Gao, Airong Su, Deyan Chen, Hongyong Song, Xilin Wu, Zhiwei Wu
Objective To express the V1/V2 domain of HIV-1 subtype CRF01_AE gp120 in eukaryotic cells, and then prepare its monoclonal antibody (mAb) and identify its antigen reactivity. Methods Eukaryotic expression vector of pTriEx-3-V1/V2CNE55 was constructed and transiently transfected into HEK293F cell line. The V1/V2-His chimera protein was purified and injected into BALB/c mice. After the fusion between spleen cells of immunized BALB/c mice and myeloma cells SP 2/0, ELISA was used for screening the positive hybridoma cell clones against the V1/V2 recombinant protein...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28392757/aspp2-plays-a-dual-role-in-gp120-induced-autophagy-and-apoptosis-of-neuroblastoma-cells
#8
Zhiying Liu, Luxin Qiao, Yulin Zhang, Yunjing Zang, Ying Shi, Kai Liu, Xin Zhang, Xiaofan Lu, Lin Yuan, Bin Su, Tong Zhang, Hao Wu, Dexi Chen
HIV invasion of the central nervous system (CNS) in the majority of patients infected with HIV-1, leads to dysfunction and injury within the CNS, showing a variety of neurological symptoms which was broadly termed HIV-associated neurocognitive disorder (HAND). But the molecular mechanisms are not completely understood. It has been suggested that apoptosis and autophagic dysfunction in neurons may play an important role in the development of HAND. Previous studies have indicated that p53 may be involved in the onset of neurological disorder in AIDS...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28390972/targeting-cell-surface-hiv-1-env-protein-to-suppress-infectious-virus-formation
#9
Arangassery Rosemary Bastian, Charles G Ang, Kantharaju Kamanna, Farida Shaheen, Yu-Hung Huang, Karyn McFadden, Caitlin Duffy, Lauren D Bailey, Ramalingam Venkat Kalyana Sundaram, Irwin Chaiken
HIV-1 Env protein is essential for host cell entry, and targeting Env remains an important antiretroviral strategy. We previously found that a peptide triazole thiol KR13 and its gold nanoparticle conjugate AuNP-KR13 directly and irreversibly inactivate the virus by targeting the Env protein, leading to virus gp120 shedding, membrane disruption and p24 capsid protein release. Here, we examined the consequences of targeting cell-surface Env with the virus inactivators. We found that both agents led to formation of non-infectious virus from transiently transfected HEK293T cells...
April 6, 2017: Virus Research
https://www.readbyqxmd.com/read/28386256/host-immune-responses-in-hiv-1-infection-the-emerging-pathogenic-role-of-siglecs-and-their-clinical-correlates
#10
REVIEW
Joanna Mikulak, Clara Di Vito, Elisa Zaghi, Domenico Mavilio
A better understanding of the mechanisms employed by HIV-1 to escape immune responses still represents one of the major tasks required for the development of novel therapeutic approaches targeting a disease still lacking a definitive cure. Host innate immune responses against HIV-1 are key in the early phases of the infection as they could prevent the development and the establishment of two hallmarks of the infection: chronic inflammation and viral reservoirs. Sialic acid-binding immunoglobulin-like lectins (Siglecs) belong to a family of transmembrane proteins able to dampen host immune responses and set appropriate immune activation thresholds upon ligation with their natural ligands, the sialylated carbohydrates...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28381572/improving-the-expression-and-purification-of-soluble-recombinant-native-like-hiv-1-envelope-glycoprotein-trimers-by-targeted-sequence-changes
#11
Rajesh P Ringe, Gabriel Ozorowski, Anila Yasmeen, Albert Cupo, Victor M Cruz Portillo, Pavel Pugach, Michael Golabek, Kimmo Rantalainen, Lauren G Holden, Christopher A Cottrell, Ian A Wilson, Rogier W Sanders, Andrew B Ward, P J Klasse, John P Moore
Soluble, recombinant native-like envelope glycoprotein (Env) trimers of various human immunodeficiency virus type 1 (HIV-1) genotypes are being developed for structural studies and as vaccine candidates aimed at the induction of broadly neutralizing antibodies (bNAbs). The prototypic design is designated SOSIP.664, but many HIV-1 env genes do not yield fully native-like trimers efficiently. One such env gene is CZA97.012 from a neutralization-resistant (Tier-2) clade C virus. As appropriately purified, native-like CZA97...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28366604/single-n277a-substitution-in-c2-of-simian-immunodeficiency-virus-envelope-influences-vaccine-elicited-cd4i-neutralizing-and-anti-v2-antibody-responses
#12
Xian Tang, Jia Guo, Lin Cheng, Caijun Sun, Li Liu, Teng Zuo, Hui Wang, Ling Chen, Linqi Zhang, Zhiwei Chen
An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified. Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells. Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals. We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain...
May 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28349243/endocytic-trafficking-of-hiv-gp120-is-mediated-by-dynamin-and-plays-a-role-in-gp120-neurotoxicity
#13
Erin D Wenzel, Alessia Bachis, Valeria Avdoshina, Francesca Taraballi, Ennio Tasciotti, Italo Mocchetti
Neurons that endocytose the human immunodeficiency virus-1 (HIV) protein gp120 exhibit neurite retraction and activation of caspase-3, suggesting that the endocytic process may be crucial for gp120-mediated neuronal injury. The goal of this study is to demonstrate that internalization and accumulation of gp120 play a role in its neurotoxic effects. In mammalian cells, endocytosis is primarily a dynamin-dependent process. To establish whether gp120 is endocytosed in a dynamin-dependent manner, we used fibroblasts in which deletion of dynamins was induced by tamoxifen...
March 27, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28348557/dendritic-cell-response-to-hiv-1-is-controlled-by-differentiation-programs-in-the-cells-and-strain-specific-properties-of-the-virus
#14
Aikaterini Nasi, Sylvie Amu, Mårten Göthlin, Marianne Jansson, Noemi Nagy, Francesca Chiodi, Bence Réthi
Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28346521/hiv-1-gp120-envelope-glycoprotein-determinants-for-cytokine-burst-in-human-monocytes
#15
Benoît Levast, Lucie Barblu, Mathieu Coutu, Jérémie Prévost, Nathalie Brassard, Adam Peres, Camille Stegen, Joaquín Madrenas, Daniel E Kaufmann, Andrés Finzi
The first step of HIV infection involves the interaction of the gp120 envelope glycoprotein to its receptor CD4, mainly expressed on CD4+ T cells. Besides its role on HIV-1 entry, the gp120 has been shown to be involved in the production of IL-1, IL-6, CCL20 and other innate response cytokines by bystander, uninfected CD4+ T cells and monocytes. However, the gp120 determinants involved in these functions are not completely understood. Whether signalling leading to cytokine production is due to CD4 or other receptors is still unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28340570/the-therapeutic-hiv-env-c5-gp41-vaccine-candidate-vacc-c5-induces-specific-t-cell-regulation-in-a-phase-i-ii-clinical-study
#16
Kristin Brekke, Maja Sommerfelt, Mats Ökvist, Anne Margarita Dyrhol-Riise, Dag Kvale
BACKGROUND: Levels of non-neutralising antibodies (AB) to the C5 domain of HIV Env gp120 are inversely related to progression of HIV infection. In this phase I/II clinical study we investigated safety of Vacc-C5, a peptide-based therapeutic vaccine candidate corresponding to C5/gp41(732-744) as well as the effects on pre-existing AB levels to C5/gp41(732-744), immune activation and T cell responses including exploratory assessments of Vacc-C5-induced T cell regulation. Our hypothesis was that exposure of the C5 peptide motif may have detrimental effects due to several of its HLA-like features and that enhancement of non-neutralising anti-C5 AB by vaccination could reduce C5 exposure and thereby chronic immune activation...
March 24, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28322598/screening-and-functional-profiling-of-small-molecule-hiv-1-entry-and-fusion-inhibitors
#17
Charline Giroud, Yuhong Du, Mariana Marin, Qui Min, Nathan T Jui, Haian Fu, Gregory B Melikyan
HIV-1 entry and fusion with target cells is an important target for antiviral therapy. However, a few currently approved treatments are not effective as monotherapy due to the emergence of drug resistance. This consideration has fueled efforts to develop new bioavailable inhibitors targeting different steps of the HIV-1 entry process. Here, a high-throughput screen was performed of a large library of 100,000 small molecules for HIV-1 entry/fusion inhibitors, using a direct virus-cell fusion assay in a 384 half-well format...
February 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28318765/in-vivo-electroporation-in-dna-vlp-prime-boost-preferentially-enhances-hiv-1-envelope-specific-igg2a-neutralizing-antibody-and-cd8-t-cell-responses
#18
Xun Huang, Qianqian Zhu, Xiaoxing Huang, Lifei Yang, Yufeng Song, Ping Zhu, Paul Zhou
Although in vivo electroporation (EP) has been utilized to improve immunogenicity in DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectors, no studies on in vivo EP in DNA-VLP prime-boost regimens against HIV-1 have been reported. Previously we developed stably transfected Drosophila S2 clones to produce HIV-1 virus-like particles (VLP) and demonstrated that priming mice twice with DNA plasmids encoding HIV-1 gp120 and gag and boosting twice with HIV-1 VLP (i.e. DDVV immunization) elicited both envelope-specific antibody and envelope and gag-specific CD8 T cell responses...
March 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28314374/hiv-1-consensus-envelope-induced-broadly-binding-antibodies
#19
R Ryan Meyerhoff, Richard M Scearce, Damon F Ogburn, Brad Lockwood, Joy Pickeral, Masa Kuraoka, Kara Anasti, Joshua Eudailey, Amanda Eaton, Melissa Cooper, Kevin Wiehe, David C Montefiori, Georgia D Tomaras, Guido Ferrari, S Munir Alam, Hua-Xin Liao, Bette Korber, Feng Gao, Barton F Haynes
Antibodies that cross-react with multiple HIV-1 envelopes (Envs) are useful reagents for characterizing Env proteins and for soluble Env capture and purification assays. We previously reported ten murine monoclonal antibodies induced by group M consensus Env, CON-6 immunization. Each demonstrated broad cross-reactivity to recombinant Envs. Here we characterized the Env epitopes to which they bind. Seven mapped to linear epitopes in gp120, five at the Env N-terminus and two at the Env C-terminus. One antibody, 13D7, bound at the gp120 N-terminus (aa 30-42), reacted with HIV-1-infected CD4+ T cells, and when expressed in a human IgG1 backbone, mediated ADCC...
March 17, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28295345/the-viral-protein-gp120-decreases-the-acetylation-of-neuronal-tubulin-potential-mechanism-of-neurotoxicity
#20
Valeria Avdoshina, Seamus P Caragher, Erin D Wenzel, Francesca Taraballi, Italo Mocchetti, G Jean Harry
The human immunodeficiency virus (HIV) envelope protein gp120 promotes axonal damage and neurite pruning, similar to that observed in HIV positive subjects with neurocognitive disorders. Thus, gp120 has been used to examine molecular and cellular pathways underlying HIV-mediated neuronal dysfunction. Gp120 binds to tubulin beta III, a component of neuronal microtubules. Microtubule function, which modulates the homeostasis of neurons, is regulated by polymerization and post-translational modifications. Based on these considerations, we tested the hypothesis that gp120 induces dynamic instability of neuronal microtubules...
March 10, 2017: Journal of Neurochemistry
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