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https://www.readbyqxmd.com/read/29118121/hiv-1-r5-macrophage-tropic-envelope-glycoprotein-trimers-bind-cd4-with-high-affinity-while-the-cd4-binding-site-on-non-macrophage-tropic-t-tropic-r5-envelopes-is-occluded
#1
Briana Quitadamo, Paul J Peters, Alexander Repik, Olivia O'Connell, Zhongming Mou, Matthew Koch, Mohan Somasundaran, Robin Brody, Katherine Luzuriaga, Aaron Wallace, Shixia Wang, Shan Lu, Sean McCauley, Jeremy Luban, Maria Duenas-Decamp, Maria Paz Gonzalez-Perez, Paul Clapham
HIV-1 R5 viruses exploit CCR5 as a coreceptor to infect both T-cells and macrophages. R5 viruses that are transmitted or derived from immune tissue and peripheral blood are mainly inefficient at mediating infection of macrophages. In contrast, highly macrophage-tropic R5 viruses predominate in brain tissue and can be detected in cerebral spinal fluid, but are infrequent in immune tissue or blood even in late disease. These mac-tropic R5 variants carry envelope glycoproteins (Envs) adapted to exploit low levels of CD4 on macrophages to induce infection...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29093095/combination-adenovirus-and-protein-vaccines-prevent-infection-or-reduce-viral-burden-after-heterologous-clade-c-shiv-mucosal-challenge
#2
Delphine C Malherbe, Jason Mendy, Lo Vang, Philip T Barnette, Jason Reed, Samir K Lakhashe, Joshua Owuor, Johannes S Gach, Alfred W Legasse, Michael K Axthelm, Celia C LaBranche, David Montefiori, Donald N Forthal, Byung Park, James M Wilson, James H McLinden, Jinhua Xiang, Jack T Stapleton, Jonah B Sacha, Barton F Haynes, Hua-Xin Liao, Ruth M Ruprecht, Jonathan Smith, Marc Gurwith, Nancy L Haigwood, Jeff Alexander
HIV vaccine development is focused on designing immunogens and delivery methods that elicit protective immunity. We evaluated a combination of Ad vectors expressing HIV 1086.C (Clade C) Envelope glycoprotein, SIV Gag p55, and human pegivirus GBV-C E2 glycoprotein. We compared replicating simian (SAd7) with non-replicating human (Ad4) adenovirus-vectored vaccines paired with recombinant proteins in a novel prime-boost regimen in rhesus macaques, with the goal of eliciting protective immunity against SHIV challenge...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29093081/analysis-of-select-hsv-1-proteins-for-restriction-of-human-immunodeficiency-virus-type-1-the-hsv-1-gm-protein-potently-restricts-hiv-1-by-preventing-the-intracellular-transport-and-processing-of-env-gp160
#3
Sachith Polpitiya Arachchige, Wyatt Henke, Ankita Pramanik, Maria Kalamvoki, Edward B Stephens
Proteins encoded by viruses that impair or shutdown specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus type 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M (gM), US3 and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference of the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29068488/human-endogenous-retroviruses-in-the-aetiology-of-ms
#4
REVIEW
T Christensen
Several lines of investigation have provided strong indications for an association between the immune-mediated, neurologic disease multiple sclerosis (MS) and human endogenous retroviruses (HERVs). Whether the relationship is causal is yet to be established. Endogenous retroviruses are pathogenic-in other species than the human. Several aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been documented, both for cells in the periphery and in the central nervous system...
November 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/29056482/solution-structure-and-membrane-interaction-of-the-cytoplasmic-tail-of-hiv-1-gp41-protein
#5
R Elliot Murphy, Alexandra B Samal, Jiri Vlach, Jamil S Saad
The cytoplasmic tail of gp41 (gp41CT) remains the last HIV-1 domain with an unknown structure. It plays important roles in HIV-1 replication such as mediating envelope (Env) intracellular trafficking and incorporation into assembling virions, mechanisms of which are poorly understood. Here, we present the solution structure of gp41CT in a micellar environment and characterize its interaction with the membrane. We show that the N-terminal 45 residues are unstructured and not associated with the membrane. However, the C-terminal 105 residues form three membrane-bound amphipathic α helices with distinctive structural features such as variable degree of membrane penetration, hydrophobic and basic surfaces, clusters of aromatic residues, and a network of cation-π interactions...
November 7, 2017: Structure
https://www.readbyqxmd.com/read/29028477/modulation-of-the-nf-%C3%AE%C2%BAb-signaling-pathway-by-the-hiv-2-envelope-glycoprotein-and-its-incomplete-bst-2-antagonism
#6
François E Dufrasne, Mara Lucchetti, Anandi Martin, Emmanuel André, Géraldine Dessilly, Benoit Kabamba, Patrick Goubau, Jean Ruelle
The HIVs have evolved by selecting means to hijack numerous host cellular factors. HIVs exploit the transcription factor NF-κB to ensure efficient LTR-driven gene transcription. However, NF-κB is primarily known to act as a key regulator of the proinflammatory and antiviral responses. Interestingly, retroviruses activate NF-κB during early stages of infection to initiate proviral genome expression while suppressing it at later stages to restrain expression of antiviral genes. During HIV-1 infection, diverse viral proteins such as Env, Nef and Vpr have been proposed to activate NF-κB activity, whereas Vpu has been shown to inhibit NF-κB activation...
October 10, 2017: Virology
https://www.readbyqxmd.com/read/29021394/hiv-1-gp120-protein-and-mvagp140-boost-immunogens-increase-immunogenicity-of-a-dna-mva-hiv-1-vaccine
#7
Xiaoying Shen, Rahul Basu, Sheetal Sawant, David Beaumont, Sue Fen Kwa, Celia LaBranche, Kelly E Seaton, Nicole L Yates, David C Montefiori, Guido Ferrari, Linda S Wyatt, Bernard Moss, S Munir Alam, Barton F Haynes, Georgia D Tomaras, Harriet L Robinson
An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia Ankara (MVA) expressing HIV-1 Env on virus like particles. Here we evaluated whether the addition of a gp120 protein in alum or MVA expressed secreted gp140 (MVAgp140) could improve immunogenicity of a DNA prime - MVA boost vaccine. Five rhesus macaques per group received two DNA primes at weeks 0 and 8 followed by three MVA boosts (with or without additional protein or MVAgp140) at weeks 18, 26 and 40...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29020058/hiv-transmitted-founder-vaccines-elicit-autologous-tier-2-neutralizing-antibodies-for-the-cd4-binding-site
#8
Nathanael P McCurley, Arban Domi, Rahul Basu, Kevin O Saunders, Celia C LaBranche, David C Montefiori, Barton F Haynes, Harriet L Robinson
Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30)...
2017: PloS One
https://www.readbyqxmd.com/read/29019351/hot-news-exosomes-as-new-players-in-hiv-pathogenesis-new-data-from-the-ias-2017
#9
Eva Poveda, Michael L Freeman
Exosomes are nanovesicles that can be released into the extracellular medium by different cell types and are considered an important system of intercellular communication. In some instances, on secretion, exosomes break down and release their content into the extracellular space. Alternatively, intact exosomes can interact with other cells and discharge their content directly into the target cell cytoplasm. Exosomes are rich in endosome-associated proteins (i.e., the tetraspanin family) but also carry different molecules in their lumen including proteins, RNAs (i...
October 11, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28986681/the-construction-and-application-of-a-cell-line-resistant-to-novel-subgroup-avian-leukosis-virus-alv-k-infection
#10
Rao Mingzhang, Zhao Zijun, Yuan Lixia, Chen Jian, Feng Min, Zhang Jie, Liao Ming, Cao Weisheng
A novel avian leukosis viruses (ALV) subgroup named ALV-K was recently isolated from Chinese indigenous chickens which is different from the subgroups (A to E and J) that have previously been reported to infect chickens. More and more ALV-K strains have recently been isolated from local breeds of Chinese chickens. However, there are no more effective diagnostic methods for ALV-K other than virus isolation followed by envelope gene sequencing and comparison. Viral infection can be blocked through expression of the viral receptor-binding protein...
October 6, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28986430/how-entry-inhibitors-synergize-to-fight-hiv
#11
REVIEW
Gregory B Melikyan
HIV fusion with the cell membrane can be inhibited by blocking coreceptor binding or by preventing fusion-inducing conformational changes in the Env protein. Logically, inhibitors that act by these two mechanisms should act synergistically, but previous studies have reported conflicting results. A new study by Ahn and Root reconciles these discordant reports by demonstrating that synergy emerges when Env engages multiple coreceptors prior to inducing fusion and when high-affinity inhibitory peptides are used, a condition that may not be satisfied in vivo...
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28982260/immunization-with-clinical-hiv-1-env-proteins-induces-broad-antibody-dependent-cellular-cytotoxicity-adcc-mediating-antibodies-in-a-rabbit-vaccination-model
#12
Ingrid Karlsson, Marie Borggren, Sanne Skov Jensen, Leo Heyndrickx, Guillaume Stewart-Jones, Gabriella Scarlatti, Anders Fomsgaard
The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, e.g., antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient antibody response, rabbits were immunized with selected antigens using different prime-boost strategies. We immunized 35 different groups of rabbits with Env antigens from clinical HIV-1 subtypes A and B, including immunization with DNA alone, protein alone and DNA prime with protein boost...
October 6, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28982126/natural-and-cross-inducible-anti-siv-antibodies-in-mauritian-cynomolgus-macaques
#13
Hongzhao Li, Mikaela Nykoluk, Lin Li, Lewis R Liu, Robert W Omange, Geoff Soule, Lukas T Schroeder, Nikki Toledo, Mohammad Abul Kashem, Jorge F Correia-Pinto, Binhua Liang, Nancy Schultz-Darken, Maria J Alonso, James B Whitney, Francis A Plummer, Ma Luo
Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline) antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10), respectively (PCS peptides), and three non-PCS Gag or Env peptides...
2017: PloS One
https://www.readbyqxmd.com/read/28978711/functional-stability-of-hiv-1-envelope-trimer-affects-accessibility-to-broadly-neutralizing-antibodies-at-its-apex
#14
Syna Kuriakose Gift, Daniel P Leaman, Lei Zhang, Arthur S Kim, Michael B Zwick
The trimeric envelope glycoprotein spike (Env) of HIV-1 is the target of vaccine development to elicit broadly neutralizing antibodies (bnAbs). Env trimer instability and heterogeneity in principle make subunit interfaces inconsistent targets for the immune response. Here, we investigate how functional stability of Env relates to neutralization sensitivity to V2 bnAbs and V3 crown antibodies that engage subunit interfaces upon binding to unliganded Env. Env heterogeneity was inferred when antibodies neutralized a mutant Env with a plateau of less than 100% percentage neutralization...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28978475/elicitation-of-neutralizing-antibodies-targeting-the-v2-apex-of-the-hiv-envelope-trimer-in-a-wild-type-animal-model
#15
James E Voss, Raiees Andrabi, Laura E McCoy, Natalia de Val, Roberta P Fuller, Terrence Messmer, Ching-Yao Su, Devin Sok, Salar N Khan, Fernando Garces, Laura K Pritchard, Richard T Wyatt, Andrew B Ward, Max Crispin, Ian A Wilson, Dennis R Burton
Recent efforts toward HIV vaccine development include the design of immunogens that can engage B cell receptors with the potential to affinity mature into broadly neutralizing antibodies (bnAbs). V2-apex bnAbs, which bind a protein-glycan region on HIV envelope glycoprotein (Env) trimer, are among the most broad and potent described. We show here that a rare "glycan hole" at the V2 apex is enriched in HIV isolates neutralized by inferred precursors of prototype V2-apex bnAbs. To investigate whether this feature could focus neutralizing responses onto the apex bnAb region, we immunized wild-type rabbits with soluble trimers adapted from these Envs...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28972148/time-course-negative-stain-electron-microscopy-based-analysis-for-investigating-protein-protein-interactions-at-the-single-molecule-level
#16
Bartek Nogal, Charles A Bowman, Andrew B Ward
Several biophysical approaches are available to study protein-protein interactions. Most approaches are conducted in bulk solution, and are therefore limited to an average measurement of the ensemble of molecular interactions. Here, we show how single-particle EM can enrich our understanding of protein-protein interactions at the single-molecule level and potentially capture states that are unobservable with ensemble methods because they are below the limit of detection or not conducted on an appropriate timescale...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28968905/yellow-fever-virus-but-not-zika-or-dengue-virus-inhibits-t-cell-receptor-mediated-t-cell-function-by-an-rna-based-mechanism
#17
James H McLinden, Nirjal Bhattarai, Jack T Stapleton, Qing Chang, Thomas M Kaufman, Suzanne L Cassel, Fayyaz S Sutterwala, Hillel Haim, Jon Houtman, Jinhua Xiang
The Flavivirus genus within the Flaviviridae is comprised of many important human pathogens including Yellow Fever virus (YFV), Dengue virus (DENV) and Zika virus (ZKV), all of which are global public health concerns. Although the related flaviviruses hepatitis C virus and human pegivirus (formerly named GBV-C) interfere with T cell receptor (TCR) signaling by novel RNA and protein based mechanisms, the effect of other flaviviruses on TCR signaling is unknown. Here, we studied the effect of YFV, DENV, and ZKV on TCR signaling...
September 2, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28945790/a-single-gp120-residue-can-affect-hiv-1-tropism-in-macaques
#18
Gregory Q Del Prete, Brandon F Keele, Jeannine Fode, Keyur Thummar, Adrienne E Swanstrom, Anthony Rodriguez, Alice Raymond, Jacob D Estes, Celia C LaBranche, David C Montefiori, Vineet N KewalRamani, Jeffrey D Lifson, Paul D Bieniasz, Theodora Hatziioannou
Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env) glycoproteins, (SHIVs) and simian-tropic HIV-1 (stHIV) strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28933684/screening-of-primary-gp120-immunogens-to-formulate-the-next-generation-polyvalent-dna-prime-protein-boost-hiv-1-vaccines
#19
Shixia Wang, Te-Hui Chou, Anthony Hackett, Veronica Efros, Yan Wang, Dong Han, Aaron Wallace, Yuxin Chen, Guangnan Hu, Shuying Liu, Paul Clapham, James Arthos, David Montefiori, Shan Lu
Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28931091/t-cell-responses-targeting-hiv-nef-uniquely-correlate-with-infected-cell-frequencies-after-long-term-antiretroviral-therapy
#20
Allison S Thomas, Kimberley L Jones, Rajesh T Gandhi, Deborah K McMahon, Joshua C Cyktor, Dora Chan, Szu-Han Huang, Ronald Truong, Alberto Bosque, Amanda B Macedo, Colin Kovacs, Erika Benko, Joseph J Eron, Ronald J Bosch, Christina M Lalama, Samuel Simmens, Bruce D Walker, John W Mellors, R Brad Jones
HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression...
September 2017: PLoS Pathogens
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