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https://www.readbyqxmd.com/read/28544005/hiv-1-p55-gag-protein-induces-senescence-of-human-bone-marrow-mesenchymal-stem-cells-and-reduces-their-capacity-to-support-expansion-of-hematopoietic-stem-cells-in-vitro
#1
Ya-Hong Yuan, Shan-Shan Zhao, Xiao-Li Wang, Zhi-Ping Teng, Dong-Sheng Li, Yi Zeng
Patients with human immunodeficiency virus-1 (HIV-1) infection often present with hematopoietic failure. As the important hematopoietic support cells in the bone marrow (BM), the bone marrow mesenchymal stem cells (BMSCs) can be impacted by HIV proteins that are released by infected cells within BM. In this study, we tested whether HIV protein p55-gag could induce senescence of BMSCs and reduce their capacity to support expansion of hematopoietic stem cells in vitro. BMSCs were chronically treated with p55-gag (BMSCgag ) for up to 20 days, and their proliferative activity and senescence makers were compared to nontreated cells (BMSCcon )...
May 25, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28540766/hiv-1-full-genome-phylogenetics-of-generalized-epidemics-in-sub-saharan-africa-impact-of-missing-nucleotide-characters-in-next-generation-sequences
#2
Oliver Ratmann, Chris Wymant, Caroline Colijn, Siva Danaviah, M Essex, Simon D W Frost, Astrid Gall, Simani Gaiseitsiwe, Mary Grabowski, Ronald Gray, Stephane Guindon, Arndt von Haeseler, Pontiano Kaleebu, Michelle Kendall, Alexey Kozlov, Justen Manasa, Bui Quang Minh, Sikhulile Moyo, Vladimir Novitsky, Rebecca Nsubuga, Sureshnee Pillay, Thomas C Quinn, David Serwadda, Deogratius Ssemwanga, Alexandros Stamatakis, Jana Trifinopoulos, Maria Wawer, Andrew Leigh Brown, Tulio de Oliveira, Paul Kellam, Deenan Pillay, Christophe Fraser
To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2,833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai...
May 25, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28539452/interactions-between-hiv-1-gag-and-viral-rna-genome-enhance-virion-assembly
#3
Kari A Dilley, Olga A Nikolaitchik, Andrea Galli, Ryan C Burdick, Louis Levine, Kelvin Li, Alan Rein, Vinay K Pathak, Wei-Shau Hu
Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28536264/exosomes-from-uninfected-cells-activate-transcription-of-latent-hiv-1
#4
Robert A Barclay, Angela Schwab, Catherine DeMarino, Yao Akpamagbo, Benjamin Lepene, Seble Kassaye, Sergey Iordanskiy, Fatah Kashanchi
HIV-1 infection causes AIDS, infecting millions worldwide. The virus can persist in a state of chronic infection due to its ability to become latent. We have previously shown a link between HIV-1 infection and exosome production. Specifically, we have reported that exosomes transport viral proteins and RNA from infected cells to neighboring uninfected cells. These viral products could then elicit an innate immune response, leading to activation of the Toll-like receptor (TLR) and NF-κB pathways. In this study, we asked whether exosomes from uninfected cells could activate latent HIV-1 in infected cells...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28511544/structural-characterization-of-membrane-bound-human-immunodeficiency-virus-1-gag-matrix-with-neutron-reflectometry
#5
Rebecca Eells, Marilia Barros, Kerry M Scott, Ioannis Karageorgos, Frank Heinrich, Mathias Lösche
The structural characterization of peripheral membrane proteins represents a tremendous challenge in structural biology due to their transient interaction with the membrane and the potential multitude of protein conformations during this interaction. Neutron reflectometry is uniquely suited to address this problem because of its ability to structurally characterize biological model systems nondestructively and under biomimetic conditions that retain full protein functionality. Being sensitive to only the membrane-bound fraction of a water-soluble peripheral protein, neutron reflectometry obtains a low-resolution average structure of the protein-membrane complex that is further refined using integrative modeling strategies...
May 16, 2017: Biointerphases
https://www.readbyqxmd.com/read/28509569/hiv-1-crf07_bc-with-a-seven-amino-acid-deletion-in-the-gag-p6-region-dominates-in-hiv-1-infected-men-who-have-sex-with-men-in-china
#6
Yue Wu, Haiying Wang, Xuqi Ren, Zhengwei Wan, Guifang Hu, Shixing Tang
We examined sequence variation in the HIV-1 gag p6 region from 27 individuals infected with HIV-1 CRF07_BC. An additional 269 gag p6 sequences of CRF07_BC from the Los Alamos National Laboratory database were also analyzed. A unique deletion of seven amino acid (aa) (p6Δ7) (aa 30-36, PIDKELY, in the HXB2 genome) was observed to exist exclusively in CRF07_BC. Indeed, 54.1% (160/296) of the CRF07_BC sequences contained the p6Δ7 mutation. The prevalence of the p6Δ7 mutation was 37.2% (29/78) and 92.3% (48/52) in CRF07_BC-infected intravenous drug users and men who have sex with men (MSM), respectively...
May 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28493367/granulocyte-macrophage-colony-stimulating-factor-a-potent-adjuvant-for-polarization-to-th-17-pattern-an-experience-on-hiv-1-vaccine-model
#7
Mehdi Mahdavi, Amir Hossein Tajik, Massoumeh Ebtekar, Roghieh Rahimi, Mohammad Mehdi Adibzadeh, Hamid Reza Moozarmpour, Mohammad Sadegh Beikverdi, Soophie Olfat, Zuhair Mohammad Hassan, Mohammad Choopani, Morteza Kameli, Christine Hartoonian
Cytokines are mediators for polarization of immune response in vaccines. Studies show that co-immunization of DNA vaccines with granulocyte-macrophage colony-stimulating factor (GM-CSF) can increase immune responses. Here, experimental mice were immunized with HIV-1tat/pol/gag/env DNA vaccine with GM-CSF and boosted with recombinant vaccine. Lymphocyte proliferation with Brdu and CTL activity, IL-4, IFN-γ, IL-17 cytokines, total antibody, and IgG1 and IgG2a isotypes were assessed with ELISA. Results show that GM-CSF as adjuvant in DNA immunization significantly increased lymphocyte proliferation and IFN-γ cytokines, but CTL response was tiny increased...
May 11, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28485382/single-cell-profiling-of-lineage-determining-transcription-factors-in-antigen-specific-cd4-t-cells-reveals-unexpected-complexity-in-recall-responses-during-immune-reconstitution
#8
Chansavath Phetsouphanh, Yin Xu, Mee Ling Munier, John J Zaunders, Anthony D Kelleher
Recent studies of protein and gene expression at the single-cell level have revealed that the memory T-cell compartment is more heterogeneous than previously acknowledged. Identifying different T helper subsets involved in memory responses at the single-cell level is thus necessary to understand the level of heterogeneity within this population. Antigen-specific CD4(+) T cells were measured using the CD25/OX40 assay together with a qualitative multiplex single-cell RT-PCR assay. Transcription profiles and subset proportions within the antigen-specific CD4(+) T-cell population were dissected...
May 9, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28483193/expression-of-complete-siv-p27-gag-and-hiv-gp120-engineered-outer-domains-targeted-by-broadly-neutralizing-antibodies-in-live-rubella-vectors
#9
Konstantin Virnik, Edmund Nesti, Cody Dail, Max Hockenbury, Yisheng Ni, Barbara K Felber, William R Schief, Ira Berkower
Infection with HIV or SIV often elicits a potent immune response to viral antigens. This includes T cells and antibodies specific for Gag and Env antigens. In contrast, when given as a vaccine, the same antigens have been weak immunogens, unable to elicit antibodies with comparable titer, durability, or neutralizing activity. We have used the live attenuated rubella vaccine strain RA27/3 as a viral vector to express HIV and SIV antigens. By mimicking an HIV infection, these vectors could elicit stronger and more durable immunity to HIV antigens...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28481902/association-of-hiv-diversity-and-virologic-outcomes-in-early-antiretroviral-treatment-hptn-052
#10
Philip J Palumbo, Ethan A Wilson, Estelle Piwowar-Manning, Marybeth McCauley, Theresa Gamble, Newton Kumwenda, Joseph Makhema, Nagalingeswaran Kumarasamy, Suwat Chariyalertsak, James G Hakim, Mina C Hosseinipour, Marineide G Melo, Sheela V Godbole, Jose H Pilotto, Beatriz Grinsztejn, Ravindre Panchia, Ying Q Chen, Myron S Cohen, Susan H Eshleman, Jessica M Fogel
Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure...
2017: PloS One
https://www.readbyqxmd.com/read/28480237/gag-specific-cd8-t-cell-proliferation-is-associated-with-higher-peripheral-blood-levels-of-transforming-growth-factor-%C3%AE-and-gut-homing-t-cells-in-youths-perinatally-infected-with-human-immunodeficiency-virus-1-the-anrs-ep38-immip-study
#11
Josiane Warszawski, Véronique Avettand-Fenoel, Christine Rouzioux, Daniel Scott-Algara, Thomas Montange, Céline Didier, Jérôme Le Chenadec, Jean-Paul Viard, Catherine Dollfus, Stéphane Blanche, Florence Buseyne
BACKGROUND: Gag-specific T lymphocytes play a key role in the control of human immunodeficiency virus (HIV) replication. Their restoration will be important for future reservoir targeting strategies. In this study, we aimed to identify immune correlates of Gag-specific CD8 T-cell proliferation in youths with perinatally acquired HIV-1 infection. METHODS: The ANRS-EP38-IMMIP study included youths of 15 to 24 years of age. Fifty-three were taking combination anti-retroviral therapy and aviremic at the time of the study and had undergone valid 5-6-carboxyfluorescein diacetate succimidyl ester-based flow cytometry T-cell proliferation assays...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28474788/in-vivo-targeting-of-protein-antigens-to-dendritic-cells-using-anti-dec-205-single-chain-antibody-improves-hiv-gag-specific-cd4-t-cell-responses-protecting-from-airway-challenge-with-recombinant-vaccinia-gag-virus
#12
Loveline N Ngu, Nadesh N Nji, Georgia E Ambada, Bertrand Sagnia, Carol Ngane Sake, Jules Colinc Tchadji, Ghislain Donald Njambe Priso, Abel Lissom, Thibau Flaurant Tchouangueu, Denis Manga Tebit, Alain Bopda Waffo, Chae Gyu Park, Ralph M Steinman, Klaus Überla, Godwin W Nchinda
INTRODUCTION: Targeting antigens to dendritic cells (DCs) in vivo via a DC-restricted endocytic receptor, DEC205, has been validated to enhance immunity in several vaccine platforms. Particularly atttractive is selected delivery of proteins to DCs in vivo because it enables proteins to be more immunogenic and provides a cheaper and effective way for repeated immunizations. METHODS: In this study, we tested the efficacy of a single chain antibody to DEC205 (scDEC) to deliver protein antigens selectively to DCs in vivo and to induce protective immunity...
March 13, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28467046/a-targeted-mass-spectrometry-assay-for-detection-of-hiv-gag-protein-following-induction-of-latent-viral-reservoirs
#13
Daniela Schlatzer, Aiman A Haqqani, Xiaolin Li, Curtis Dobrowolski, Mark R Chance, John C Tilton
During early infection, HIV-1 establishes a reservoir of latently infected cells that persist during antiretroviral therapy. These reservoirs are considered the primary obstacle to eradicating HIV-1 from patients, and multiple strategies are being investigated to eliminate latently infected cells. Measuring the reservoir size using an affordable and scalable assay is critical as these approaches move into clinical trials: the current "gold-standard" viral outgrowth assay is costly, labor-intensive, and requires large numbers of cells...
May 3, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28464042/immune-activation-and-hiv-specific-t-cell-responses-are-modulated-by-a-cyclooxygenase-2-inhibitor-in-untreated-hiv-infected-individuals-an-exploratory-clinical-trial
#14
Christian Prebensen, Marius Trøseid, Thor Ueland, Anders Dahm, Per Morten Sandset, Ingeborg Aaberge, Kristian Waalen, Anne Ma Dyrhol-Riise, Kjetil Taskén, Dag Kvale
Pathologically elevated immune activation and inflammation contribute to HIV disease progression and immunodeficiency, potentially mediated by elevated levels of prostaglandin E2, which suppress HIV-specific T cell responses. We have previously shown that a high dose of the cyclooxygenase-2 inhibitor celecoxib can reduce HIV-associated immune activation and improve IgG responses to T cell-dependent vaccines. In this follow-up study, we included 56 HIV-infected adults, 28 antiretroviral therapy (ART)-naïve and 28 on ART with undetectable plasma viremia but CD4 counts below 500 cells/μL...
2017: PloS One
https://www.readbyqxmd.com/read/28458735/features-of-maternal-hiv-1-associated-with-lack-of-vertical-transmission
#15
REVIEW
Nafees Ahmad, Aamir N Ahmad, Shahid N Ahmad
HIV-1 is transmitted from mother-to-child (vertical transmission) at an estimated rate of approximately 30% without any antiretroviral therapy (ART). However, administration of ART during pregnancy considerably diminishes the rate of mother-to-child transmission of HIV-1, which has become a standard of perinatal care in HIV-infected pregnant females in developed countries. Moreover, a majority of children born to HIV-infected mothers are uninfected without any ART. In addition, characteristics of HIV-1 and/or cellular factors in the mothers may play a role in influencing or preventing vertical transmission...
2017: Open Virology Journal
https://www.readbyqxmd.com/read/28458036/a-heterologous-prime-boosting-strategy-with-replicating-vaccinia-virus-vectors-and-plant-produced-hiv-1-gag-dgp41-virus-like-particles
#16
Lydia R Meador, Sarah A Kessans, Jacquelyn Kilbourne, Karen V Kibler, Giuseppe Pantaleo, Mariano Esteban Roderiguez, Joseph N Blattman, Bertram L Jacobs, Tsafrir S Mor
Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation...
April 27, 2017: Virology
https://www.readbyqxmd.com/read/28454672/discovery-of-a-novel-and-potent-class-of-anti-hiv-1-maturation-inhibitors-with-improved-virology-profile-against-gag-polymorphisms
#17
Jun Tang, Stacey A Jones, Jerry L Jeffrey, Sonia R Miranda, Cristin M Galardi, David M Irlbeck, Kevin W Brown, Charlene B McDanal, Brian A Johns
A new class of betulin-derived α-keto amides was identified as HIV-1 maturation inhibitors. Through lead optimization, GSK8999 was identified with IC50 values of 17nM, 23nM, 25nM, and 8nM for wild type, Q369H, V370A, and T371A respectively. When tested in a panel of 62 HIV-1 isolates covering a diversity of CA-SP1 genotypes including A, AE, B, C, and G using a PBMC based assay, GSK8999 was potent against 57 of 62 isolates demonstrating an improvement over the first generation maturation inhibitor BVM. The data disclosed here also demonstrated that the new α-keto amide GSK8999 has a mechanism of action consistent with inhibition of the proteolytic cleavage of CA-SP1...
April 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28449096/two-ribosome-recruitment-sites-direct-multiple-translation-events-within-hiv1-gag-open-reading-frame
#18
Jules Deforges, Sylvain de Breyne, Melissa Ameur, Nathalie Ulryck, Nathalie Chamond, Afaf Saadi, Yann Ponty, Theophile Ohlmann, Bruno Sargueil
In the late phase of the HIV virus cycle, the unspliced genomic RNA is exported to the cytoplasm for the necessary translation of the Gag and Gag-pol polyproteins. Three distinct translation initiation mechanisms ensuring Gag production have been described with little rationale for their multiplicity. The Gag-IRES has the singularity to be located within Gag ORF and to directly interact with ribosomal 40S. Aiming at elucidating the specificity and the relevance of this interaction, we probed HIV-1 Gag-IRES structure and developed an innovative integrative modelling strategy to take into account all the gathered information...
April 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28446667/disparate-contributions-of-human-retrovirus-capsid-subdomains-to-gag-gag-oligomerization-virus-morphology-and-particle-biogenesis
#19
Jessica L Martin, Luiza Mendonça, Isaac Angert, Joachim D Mueller, Wei Zhang, Louis M Mansky
The capsid domain (CA) of the retroviral Gag protein is a primary determinant of Gag oligomerization, which is a critical step for immature Gag lattice formation and virus particle budding. Although the human immunodeficiency virus type 1 (HIV-1) CA carboxy-terminal domain (CTD) is essential for CA-CA interactions, the CA CTD has been suggested to be largely dispensable for human T-cell leukemia virus type 1 (HTLV-1) particle biogenesis. To more clearly define the roles of the HTLV-1 CA amino-terminal domain (NTD) and CA CTD in particle biogenesis, we generated and analyzed a panel of Gag proteins with chimeric HIV-1/HTLV-1 CA domains...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446240/molecular-mechanisms-by-which-herv-k-gag-interferes-with-hiv-1-gag-assembly-and-particle-infectivity
#20
Kazuaki Monde, Hiromi Terasawa, Yusuke Nakano, Ferri Soheilian, Kunio Nagashima, Yosuke Maeda, Akira Ono
BACKGROUND: Human endogenous retroviruses (HERVs), the remnants of ancient retroviral infections, constitute approximately 8% of human genomic DNA. Since HERV-K Gag expression is induced by HIV-1 Tat in T cells, induced HERV-K proteins could affect HIV-1 replication. Indeed, previously we showed that HERV-K Gag and HIV-1 Gag coassemble and that this appears to correlate with the effect of HERV-K Gag expression on HIV-1 particle release and its infectivity. We further showed that coassembly requires both MA and NC domains, which presumably serve as scaffolding for Gag via their abilities to bind membrane and RNA, respectively...
April 26, 2017: Retrovirology
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