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https://www.readbyqxmd.com/read/29142124/truncating-the-gp41-cytoplasmic-tail-of-siv-decreases-sensitivity-to-neutralizing-antibodies-without-increasing-envelope-content-of-virions
#1
Ellen White, Fan Wu, Elena Chertova, Julian Bess, James D Roser, Jeffrey D Lifson, Vanessa M Hirsch
An incomplete understanding of native HIV and SIV envelope glycoprotein (Env) impedes the development of structural models of Env and vaccine design. This shortcoming is due in part to the low number of Env trimers on virus particles. For SIV, this low expression can be counteracted by truncating the cytoplasmic tail (CT) of Env. CT truncation has been shown to increase Env incorporation into the virion and is commonly used in vaccine and imaging studies, but its effects on viral antigenicity have not been fully elucidated...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29098809/gp41-and-gag-amino-acids-linked-to-hiv-1-protease-inhibitor-based-second-line-failure-in-hiv-1-subtype-a-from-western-kenya
#2
Mia Coetzer, Lauren Ledingham, Lameck Diero, Emmanuel Kemboi, Millicent Orido, Rami Kantor
INTRODUCTION: Failure of protease-inhibitor (PI)-based second-line antiretroviral therapy (ART) with medication adherence but no protease drug resistance mutations (DRMs) is not well understood. This study investigated the involvement of gp41 and gag as alternative mechanisms, not captured by conventional resistance testing and particularly relevant in resource-limited settings where third-line ART is limited. METHODS: We evaluated gp41 and gag for unique amino acids in seven subtype A infected Kenyans failing second-line therapy with no PI resistance yet detectable lopinavir (query dataset), compared to seven similar-setting patients with PI resistance or undetectable lopinavir and 69 publically available subtype A Kenyan whole-genomes sequences...
November 2017: Journal of the International AIDS Society
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/29056482/solution-structure-and-membrane-interaction-of-the-cytoplasmic-tail-of-hiv-1-gp41-protein
#4
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/29046462/distinct-roles-of-cellular-escrt-i-and-escrt-iii-proteins-in-efficient-entry-and-egress-of-budded-virions-of-autographa-californica-multiple-nucleopolyhedrovirus
#5
Qi Yue, Qianlong Yu, Qi Yang, Ye Xu, Ya Guo, Gary W Blissard, Zhaofei Li
The endosomal sorting complex required for transport (ESCRT) machinery is necessary for budding by many enveloped viruses. Recently, it was demonstrated that Vps4, the key regulator for recycling of the ESCRT-III complex, is required for efficient infection of the baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV). However, ESCRT assembly, regulation and function are complex and little is known regarding details of participation of specific ESCRT complexes in AcMNPV infection. In this study, the core components of ESCRT-I (Tsg101 and Vps28) and ESCRT-III (Vps2B, Vps20, Vps24, Snf7, Vps46, and Vps60) were cloned from Spodoptera frugiperda Using a viral complementation system and RNAi assays, we found that ESCRT-I and ESCRT-III complexes are required for efficient entry of AcMNPV into insect cells...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29046160/construction-and-production-of-hiv-vlp-harboring-mper-v3-for-potential-vaccine-study
#6
Tohidi Fatemeh, Sadat Seyed Mehdi, Bolhassani Azam, Yaghobi Ramin
Vaccine against HIV-1 is not currently available. In present, Virus like particles (VLPs) as effective strategy was used in several vaccine developing. Two conserved sequences; V3 loop of gp120 and the membrane-proximal external region (MPER) of gp41 are dominant sites for vaccine studies. In this study, we used fusion gene of MPER and V3 to product recombinant VLPs and introduced a novel retroviral VLPs harboring high copy of MPER-V3 for HIV-1 vaccine design. The pEGFP-N1 plasmid harboring MPER-V3 sequence with Vpr linker was constructed...
October 17, 2017: Current HIV Research
https://www.readbyqxmd.com/read/29035947/cross-reactivity-of-hiv-vaccine-responses-and-the-microbiome
#7
Wilton B Williams, Qifeng Han, Barton F Haynes
PURPOSE OF REVIEW: A successful HIV-type 1 (HIV-1) vaccine will require immunogens that induce protective immune responses. However, recent studies suggest that the response to HIV-1 and perhaps other viruses may be altered by immune system exposure to intestinal microbiota-antigens. This review will discuss select aspects of these studies. RECENT FINDINGS: Naïve CD4 T and B cell repertoires can be imprinted by intestinal microbiota-antigens to respond to virus epitopes prior to virus infection...
October 14, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28970835/immunologic-insights-on-the-membrane-proximal-external-region-a-major-human-immunodeficiency-virus-type-1-vaccine-target
#8
REVIEW
Luis M Molinos-Albert, Bonaventura Clotet, Julià Blanco, Jorge Carrillo
Broadly neutralizing antibodies (bNAbs) targeting conserved regions within the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein (Env) can be generated by the human immune system and their elicitation by vaccination will be a key point to protect against the wide range of viral diversity. The membrane proximal external region (MPER) is a highly conserved region within the Env gp41 subunit, plays a major role in membrane fusion and is targeted by naturally induced bNAbs. Therefore, the MPER is considered as an attractive vaccine target...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28966263/creation-of-functional-molecules-based-on-biomolecular-interactions-development-toward-chemical-biology
#9
Wataru Nomura
Interactions between bio-macromolecules such as proteins, DNA, and polysaccharides play pivotal roles in maintaining homeostasis in living systems. For elucidating the function of biomolecules, peptides are powerful tools, compared to native proteins, because of their lower molecular weights, compatibility with chemical modification, and predictability of interaction with the target molecules. These advantages enabled us to develop peptide-based functional molecules. However, for the purposes of controlling or regulating biomolecule functions, designing artificial proteins is also an effective approach...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28912582/evolution-of-gag-and-gp41-in-patients-receiving-ritonavir-boosted-protease-inhibitors
#10
Justen Manasa, Vici Varghese, Sergei L Kosakovsky Pond, Soo-Yon Rhee, Philip L Tzou, W Jeffrey Fessel, Karen S Jang, Elizabeth White, Thorsteinn Rögnvaldsson, David A Katzenstein, Robert W Shafer
Several groups have proposed that genotypic determinants in gag and the gp41 cytoplasmic domain (gp41-CD) reduce protease inhibitor (PI) susceptibility without PI-resistance mutations in protease. However, no gag and gp41-CD mutations definitively responsible for reduced PI susceptibility have been identified in individuals with virological failure (VF) while receiving a boosted PI (PI/r)-containing regimen. To identify gag and gp41 mutations under selective PI pressure, we sequenced gag and/or gp41 in 61 individuals with VF on a PI/r (n = 40) or NNRTI (n = 20) containing regimen...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878072/high-throughput-protein-engineering-improves-the-antigenicity-and-stability-of-soluble-hiv-1-envelope-glycoprotein-sosip-trimers
#11
Jonathan T Sullivan, Chidananda Sulli, Alberto Nilo, Anila Yasmeen, Gabriel Ozorowski, Rogier W Sanders, Andrew B Ward, P J Klasse, John P Moore, Benjamin J Doranz
Soluble envelope glycoprotein (Env) trimers (SOSIP.664 gp140) are attractive HIV-1 vaccine candidates, with structures that mimic the native membrane-bound Env spike (gp160). Since engineering trimers can be limited by the difficulty of rationally predicting beneficial mutations, here we used a more comprehensive mutagenesis approach with the goal of identifying trimer variants with improved antigenic and stability properties. We created 341 cysteine pairs at predicted points of stabilization throughout gp140, 149 proline residue substitutions at every residue of the gp41 ectodomain, and 362 space-filling residue substitutions at every hydrophobic and aromatic residue in gp140...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28845271/a3%C3%A2-genetic-analysis-and-natural-polymorphisms-in-hiv-1-gp41-isolates-from-maputo-mozambique
#12
Nália Ismael, Dulce Bila, Diana Mariani, Adolfo Vubil, Nedio Mabunda, Celina Abreu, Ilesh Jani, Amilcar Tanuri
No abstract text is available yet for this article.
March 2017: Virus Evolution
https://www.readbyqxmd.com/read/28834745/improving-the-immunogenicity-of-native-like-hiv-1-envelope-trimers-by-hyperstabilization
#13
Alba Torrents de la Peña, Jean-Philippe Julien, Steven W de Taeye, Fernando Garces, Miklos Guttman, Gabriel Ozorowski, Laura K Pritchard, Anna-Janina Behrens, Eden P Go, Judith A Burger, Edith E Schermer, Kwinten Sliepen, Thomas J Ketas, Pavel Pugach, Anila Yasmeen, Christopher A Cottrell, Jonathan L Torres, Charlotte D Vavourakis, Marit J van Gils, Celia LaBranche, David C Montefiori, Heather Desaire, Max Crispin, Per Johan Klasse, Kelly K Lee, John P Moore, Andrew B Ward, Ian A Wilson, Rogier W Sanders
The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28834275/synthesis-biological-evaluation-and-molecular-docking-studies-of-novel-4-arylpyridin-1-4h-yl-benzoic-acid-derivatives-as-anti-hiv-1-agents
#14
Saghi Sepehri, Sepehr Soleymani, Rezvan Zabihollahi, Mohammad R Aghasadeghi, Mehdi Sadat, Lotfollah Saghaie, Afshin Fassihi
The structural similarities between N1 substituted 1,4-dihydropyridines and the known gp41 inhibitors, NB-2 and NB-64, were considered in the current research for the design of some novel anti-HIV-1 agents. A series of novel 4-arylpyridin-1(4H)-yl) benzoic acid derivatives were synthesized and after a comprehensive structural elucidation were screened for in vitro anti-HIV-1 activity. Most of the tested compounds displayed moderate to good inhibitory activity against HIV-1 growth and were evaluated for in vitro cytotoxic activity using XTT assay at the concentration of 100 μM...
August 21, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28832407/prevalence-and-clinical-impacts-of-hiv-1-intersubtype-recombinants-in-uganda-revealed-by-near-full-genome-population-and-deep-sequencing-approaches
#15
Guinevere Q Lee, David R Bangsberg, Theresa Mo, Chris Lachowski, Chanson J Brumme, Wendy Zhang, Viviane D Lima, Yap Boum, Bosco Bwana Mwebesa, Conrad Muzoora, Iren Andia, Yona Mbalibulha, Annet Kembabazi, Ryan Carroll, Mark J Siedner, Jessica E Haberer, A Rain Mocello, Simone H Kigozi, Peter W Hunt, Jeffrey N Martin, P Richard Harrigan
OBJECTIVES: HIV-1 subtypes A1 and D cocirculate in a rural community in Mbarara, Uganda. This study examines HIV-1 intersubtype recombination in this community under a full-genome sequencing context. We aim to estimate prevalence, examine time trends, and test for clinical correlates and outcomes associated with intersubtype recombinants. METHODS: Near-full-genome HIV-1 Sanger sequence data were collected from plasma samples of 504 treatment-naïve individuals, who then received protease inhibitor or nonnucleoside reverse transcriptase inhibitor-containing regimens and were monitored for up to 7...
November 13, 2017: AIDS
https://www.readbyqxmd.com/read/28811070/evaluation-of-sequence-variability-in-hiv-1-gp41-c-peptide-helix-grafted-proteins
#16
Rachel L Tennyson, Susanne N Walker, Terumasa Ikeda, Reuben S Harris, Brian R McNaughton
Many therapeutically-relevant protein-protein interactions (PPIs) have been reported that feature a helix and helix-binding cleft at the interface. Given this, different approaches to disrupting such PPIs have been developed. While short peptides (<15 amino acids) typically do not fold into a stable helix, researchers have reported chemical approaches to constraining helix structure. However, these approaches rely on laborious, and often expensive, chemical synthesis and purification. Our premise is that protein-based solutions that stabilize a therapeutically-relevant helix offer a number of advantages...
August 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28797705/effects-of-hiv-1-gp41-derived-virucidal-peptides-on-virus-like-lipid-membranes
#17
Pablo Carravilla, Antonio Cruz, Itziar Martin-Ugarte, Itziar R Oar-Arteta, Johanna Torralba, Beatriz Apellaniz, Jesús Pérez-Gil, José Requejo-Isidro, Nerea Huarte, José L Nieva
Membrane fusion induced by the envelope glycoprotein enables the intracellular replication of HIV-1; hence, this process constitutes a major target for antiretroviral compounds. It has been proposed that peptides having propensity to interact with membrane interfaces might exert broad antiviral activity against enveloped viruses. To test this hypothesis, in this contribution we have analyzed the antiviral effects of peptides derived from the membrane-proximal external region and the transmembrane domain of the envelope glycoprotein subunit gp41, which display different degrees of interfacial hydrophobicity...
September 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28794027/hiv-dna-adenovirus-multiclade-envelope-vaccine-induces-gp41-antibody-immunodominance-in-rhesus-macaques
#18
Qifeng Han, Wilton B Williams, Kevin O Saunders, Kelly E Seaton, Kevin J Wiehe, Nathan Vandergrift, Tarra A Von Holle, Ashley M Trama, Robert J Parks, Kan Luo, Thaddeus C Gurley, Thomas B Kepler, Dawn J Marshall, David C Montefiori, Laura L Sutherland, Munir S Alam, John F Whitesides, Cindy M Bowman, Sallie R Permar, Barney S Graham, John R Mascola, Patrick C Seed, Koen K A Van Rompay, Georgia D Tomaras, M Anthony Moody, Barton F Haynes
Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28790381/selective-cytotoxicity-of-a-novel-immunotoxin-based-on-pulchellin-a-chain-for-cells-expressing-hiv-envelope
#19
Mohammad Sadraeian, Francisco E G Guimarães, Ana P U Araújo, David K Worthylake, Louis Jr LeCour, Seth H Pincus
Immunotoxins (ITs), which consist of antibodies conjugated to toxins, have been proposed as a treatment for cancer and chronic infections. To develop and improve the ITs, different toxins such as ricin, have been used, aiming for higher efficacy against target cells. The toxin pulchellin, isolated from the Abrus pulchellus plant, has similar structure and function as ricin. Here we have compared two plant toxins, recombinant A chains from ricin (RAC) and pulchellin (PAC) toxins, for their ability to kill HIV Env-expressing cells...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783671/potent-and-broad-hiv-neutralizing-antibodies-in-memory-b-cells-and-plasma
#20
LaTonya D Williams, Gilad Ofek, Sebastian Schätzle, Jonathan R McDaniel, Xiaozhi Lu, Nathan I Nicely, Liming Wu, Caleb S Lougheed, Todd Bradley, Mark K Louder, Krisha McKee, Robert T Bailer, Sijy O'Dell, Ivelin S Georgiev, Michael S Seaman, Robert J Parks, Dawn J Marshall, Kara Anasti, Guang Yang, Xiaoyan Nie, Nancy L Tumba, Kevin Wiehe, Kshitij Wagh, Bette Korber, Thomas B Kepler, S Munir Alam, Lynn Morris, Gift Kamanga, Myron S Cohen, Mattia Bonsignori, Shi-Mao Xia, David C Montefiori, Garnett Kelsoe, Feng Gao, John R Mascola, M Anthony Moody, Kevin O Saunders, Hua-Xin Liao, Georgia D Tomaras, George Georgiou, Barton F Haynes
Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1-specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1-infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage...
January 27, 2017: Science Immunology
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