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https://www.readbyqxmd.com/read/28086981/does-antiretroviral-treatment-change-hiv-1-codon-usage-patterns-in-its-genes-a-preliminary-bioinformatics-study
#1
Navaneethan Palanisamy, Nathan Osman, Frédéric Ohnona, Hong-Tao Xu, Bluma Brenner, Thibault Mesplède, Mark A Wainberg
BACKGROUND: Codon usage bias has been described for various organisms and is thought to contribute to the regulation of numerous biological processes including viral infections. HIV-1 codon usage has been previously shown to be different from that of other viruses and man. It is evident that the antiretroviral drugs used to restrict HIV-1 replication also select for resistance variants. We wanted to test whether codon frequencies in HIV-1 sequences from treatment-experienced patients differ from those of treatment-naive individuals due to drug pressure affecting codon usage bias...
January 7, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28077659/hiv-controllers-exhibit-enhanced-frequencies-of-mhc-class-ii-tetramer-gag-specific-cd4-t-cells-in-chronic-clade-c-hiv-1-infection
#2
Faatima Laher, Srinika Ranasinghe, Filippos Porichis, Nikoshia Mewalal, Karyn Pretorius, Nasreen Ismail, Søren Buus, Anette Stryhn, Mary Carrington, Bruce D Walker, Thumbi Ndung'u, Zaza M Ndhlovu
: Immune control of viral infections is heavily dependent on helper CD4(+) T cell function. However, understanding the contribution of HIV-specific CD4(+) T cell responses to immune protection against HIV-1, particularly in clade C infection remains incomplete. Recently, MHC class II tetramers have emerged as a powerful tool for interrogating antigen specific CD4(+) T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4(+) T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to viral load of HIV-specific CD4(+) T cell responses in a cohort of untreated HIV clade C infected persons...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077649/tcr-clonotype-specific-differences-in-inhibitory-activity-of-hiv-1-cytotoxic-t-cell-clones-is-not-mediated-by-tcr-alone
#3
Nina C Flerin, Huabiao Chen, Tynisha D Glover, Pedro A Lamothe, Jian Hua Zheng, Justin W Fang, Zaza M Ndhlovu, Evan W Newell, Mark M Davis, Bruce D Walker, Harris Goldstein
: Functional analysis of T cell responses in HIV-infected individuals has indicated that virus-specific CD8(+) T cells with superior antiviral efficacy are well represented in HIV-1 controllers but are rare or absent in HIV-1 progessors. To define the role of individual TCR clonotypes in differential antiviral CD8(+) T cell function, we performed detailed functional and mass cytometric cluster analysis of multiple CD8(+) T cell clones recognizing the identical HLA-B*2705-restricted HIV-1 epitope KK10 (KRWIILGLNK)...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077644/ultrasensitive-hiv-1-p24-detects-single-infected-cells-and-differences-in-reservoir-induction-by-latency-reversal-agents
#4
Caroline Pereira Bittencourt Passaes, Timothée Bruel, Jérémie Decalf, Annie David, Mathieu Angin, Valerie Monceaux, Michaela Muller-Trutwin, Nicolas Noel, Katia Bourdic, Olivier Lambotte, Matthew L Albert, Darragh Duffy, Olivier Schwartz, Asier Sáez-Cirión
: The existence of HIV reservoirs in infected individuals under cART represents a major obstacle towards cure. Viral reservoirs are assessed by quantification of HIV nucleic acids, which does not discriminate between infectious and defective viruses, or by viral outgrowth assays, which requires large number of cells and long-term cultures. Here, we used an ultrasensitive p24 digital assay, which we report to be 1000 fold more sensitive than classical ELISA in the quantification of HIV-1 Gag p24 production in HIV-infected individuals samples...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077588/first-in-human-evaluation-of-the-safety-and-immunogenicity-of-an-intranasally-administered-replication-competent-sendai-virus-vectored-hiv-type-1-gag-vaccine-induction-of-potent-t-cell-or-antibody-responses-in-prime-boost-regimens
#5
Julien Nyombayire, Omu Anzala, Brian Gazzard, Etienne Karita, Philip Bergin, Peter Hayes, Jakub Kopycinski, Gloria Omosa-Manyonyi, Akil Jackson, Jean Bizimana, Bashir Farah, Eddy Sayeed, Christopher L Parks, Makoto Inoue, Takashi Hironaka, Hiroto Hara, Tsugumine Shu, Tetsuro Matano, Len Dally, Burc Barin, Harriet Park, Jill Gilmour, Angela Lombardo, Jean-Louis Excler, Patricia Fast, Dagna S Laufer, Josephine H Cox
BACKGROUND:  We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. METHODS:  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH)...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28073435/evaluation-of-the-efficacy-of-a-therapeutic-hiv-vaccine-by-in-vitro-stimulation-assay
#6
Xiaozhou He, Wandi Wang, Ke Xu, Xia Feng, Yi Zeng
A novel method for HIV vaccine efficacy evaluation was established and the experimental conditions optimized. This novel method was then applied to determine whether a recombinant adenovirus type 5 HIV therapeutic vaccine expressing Gag antigen (Ad5-HIVgag) could stimulate HIV-specific cellular responses in vitro. The results indicated that HIV-specific IFN-gama production lymphocytes were induced by the Ad5-HIVgag vaccine. Compared with other methods, this in vitro stimulation method is safe and time-efficient, and the result is more intuitive...
January 4, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28068781/complex-subtype-diversity-of-hiv-1-among-drug-users-in-major-kenyan-cities
#7
Kamini Gounder, Micah Oyaro, Nagavelli Padayachi, Thando Mbali Zulu, Tulio de Oliveira, John Wylie, Thumbi Ndung'u
Drug users are increasingly recognized as a key population driving HIV spread in sub-Saharan Africa. To determine HIV-1 subtypes circulating in this population group and explore possible geographic differences, we analyzed HIV-1 sequences among drug users from Nairobi, Mombasa and Kisumu in Kenya. We sequenced gag and env from 55 drug users. Subtype analysis from 220 gag clonal sequences from 54/55 participants (median=4/participant) showed that 44.4% were A, 16.7% were C, 3.7% were D and 35.2% were intersubtype recombinants...
January 9, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28060886/point-of-care-p24-infant-testing-for-hiv-may-increase-patient-identification-despite-low-sensitivity
#8
Bindiya Meggi, Timothy Bollinger, Nédio Mabunda, Adolfo Vubil, Ocean Tobaiwa, Jorge I Quevedo, Osvaldo Loquiha, Lara Vojnov, Trevor F Peter, Ilesh V Jani
The long delay in returning test results during early infant diagnosis of HIV (EID) often causes loss-to-follow-up prior to antiretroviral treatment (ART) initiation in resource-limited settings. A point-of-care (POC) test may help overcome these challenges. We evaluated the performance of the LYNX p24 Antigen POC test in Mozambique. 879 HIV-exposed infants under 18 months of age were enrolled consecutively at three primary healthcare clinics (PHC). Lancet heel-drawn blood was tested on-site by nurses using a prototype POC test for HIV Gag p24 antigen detection...
2017: PloS One
https://www.readbyqxmd.com/read/28053097/subcellular-localization-of-hiv-1-gag-pol-mrnas-regulates-sites-of-virion-assembly
#9
Jordan T Becker, Nathan M Sherer
: HIV-1 full-length, unspliced RNAs serve dual roles in the cytoplasm as mRNAs encoding the Gag and Gag-Pol capsid proteins as well as genomic RNAs (gRNAs) packaged by Gag into virions undergoing assembly at the plasma membrane (PM). Because Gag is sufficient to drive assembly of virus-like particles even in the absence of gRNA binding, whether viral RNA trafficking plays an active role in the native assembly pathway is unknown. In this study we tested the effects of modulating the cytoplasmic abundance or distribution of full-length viral RNAs on Gag trafficking and assembly in the context of single cells...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28034670/assays-for-precise-quantification-of-total-including-short-and-elongated-hiv-1-transcripts
#10
Philipp Kaiser, Sunil K Joshi, Peggy Kim, Peilin Li, Hongbing Liu, Andrew P Rice, Joseph K Wong, Steven A Yukl
Despite intensive study, it is unclear which mechanisms are responsible for latent HIV infection in vivo. One potential mechanism is inhibition of HIV transcriptional elongation, which results in short abortive transcripts containing the trans-activation response (TAR) region. Because the relative levels of total (including short) and processive transcripts provide measures of HIV transcriptional initiation and elongation, there is a compelling need for techniques that accurately measure both. Nonetheless, prior assays for total transcripts have been semi-quantitative and have seen limited application to patient samples...
December 27, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/28034301/mechanistic-differences-between-hiv-1-and-siv-nucleocapsid-proteins-and-cross-species-hiv-1-genomic-rna-recognition
#11
Klara Post, Erik D Olson, M Nabuan Naufer, Robert J Gorelick, Ioulia Rouzina, Mark C Williams, Karin Musier-Forsyth, Judith G Levin
BACKGROUND: The nucleocapsid (NC) domain of HIV-1 Gag is responsible for specific recognition and packaging of genomic RNA (gRNA) into new viral particles. This occurs through specific interactions between the Gag NC domain and the Psi packaging signal in gRNA. In addition to this critical function, NC proteins are also nucleic acid (NA) chaperone proteins that facilitate NA rearrangements during reverse transcription. Although the interaction with Psi and chaperone activity of HIV-1 NC have been well characterized in vitro, little is known about simian immunodeficiency virus (SIV) NC...
December 29, 2016: Retrovirology
https://www.readbyqxmd.com/read/28027665/three-year-durability-of-immune-responses-induced-by-hiv-dna-and-hiv-modified-vaccinia-virus-ankara-and-effect-of-a-late-hiv-mva-boost-in-tanzanian-volunteers
#12
Agricola Joachim, Patricia J Munseri, Charlotta Nilsson, Muhammad Bakari, Said Aboud, Eligius F Lyamuya, Teghesti Tecleab, Valentina Liakina, Gabriella Scarlatti, Merlin Robb, Patricia Earl, Bernard Moss, Britta Wahren, Fred Mhalu, Guido Ferarri, Eric Sandström, Gunnel Biberfeld
We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization three years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100)...
December 27, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28008947/self-assembly-of-hiv-1-gag-protein-on-lipid-membranes-generates-pi-4-5-p2-cholesterol-nanoclusters
#13
Naresh Yandrapalli, Quentin Lubart, Hanumant S Tanwar, Catherine Picart, Johnson Mak, Delphine Muriaux, Cyril Favard
The self-assembly of HIV-1 Gag polyprotein at the inner leaflet of the cell host plasma membrane is the key orchestrator of virus assembly. The binding between Gag and the plasma membrane is mediated by specific interaction of the Gag matrix domain and the PI(4,5)P2 lipid (PIP2). It is unknown whether this interaction could lead to local reorganization of the plasma membrane lipids. In this study, using model membranes, we examined the ability of Gag to segregate specific lipids upon self-assembly. We show for the first time that Gag self-assembly is responsible for the formation of PIP2 lipid nanoclusters, enriched in cholesterol but not in sphingomyelin...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28008945/using-nearly-full-genome-hiv-sequence-data-improves-phylogeny-reconstruction-in-a-simulated-epidemic
#14
Gonzalo Yebra, Emma B Hodcroft, Manon L Ragonnet-Cronin, Deenan Pillay, Andrew J Leigh Brown
HIV molecular epidemiology studies analyse viral pol gene sequences due to their availability, but whole genome sequencing allows to use other genes. We aimed to determine what gene(s) provide(s) the best approximation to the real phylogeny by analysing a simulated epidemic (created as part of the PANGEA_HIV project) with a known transmission tree. We sub-sampled a simulated dataset of 4662 sequences into different combinations of genes (gag-pol-env, gag-pol, gag, pol, env and partial pol) and sampling depths (100%, 60%, 20% and 5%), generating 100 replicates for each case...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28002960/characterization-of-new-cationic-n-n-dimethyl-70-fulleropyrrolidinium-iodide-derivatives-as-potent-hiv-1-maturation-inhibitors
#15
Edison Castro, Zachary S Martinez, Chang-Soo Seong, Andrea Cabrera-Espinoza, Mauro Ruiz, Andrea Hernandez Garcia, Federico Valdez, Manuel Llano, Luis Echegoyen
HIV-1 maturation can be impaired by altering protease (PR) activity, the structure of the Gag-Pol substrate, or the molecular interactions of viral structural proteins. Here we report the synthesis and characterization of new cationic N,N-dimethyl[70]fulleropyrrolidinium iodide derivatives that inhibit more than 99% of HIV-1 infectivity at low micromolar concentrations. Analysis of the HIV-1 life cycle indicated that these compounds inhibit viral maturation by impairing Gag and Gag-Pol processing. Importantly, fullerene derivatives 2a-c did not inhibit in vitro PR activity and strongly interacted with HIV immature capsid protein in pull-down experiments...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27999036/role-of-gag-mutations-in-pi-resistance-in-the-swiss-hiv-cohort-study-bystanders-or-contributors
#16
K Kletenkov, D Hoffmann, J Böni, S Yerly, V Aubert, F Schöni-Affolter, D Struck, J Verheyen, T Klimkait
BACKGROUND: HIV Gag mutations have been reported to confer PI drug resistance. However, clinical implications are still controversial and most current genotyping algorithms consider solely the protease gene for assessing PI resistance. OBJECTIVES: Our goal was to describe for HIV infections in Switzerland the potential role of the C-terminus of Gag (NC-p6) in PI resistance. We aimed to characterize resistance-relevant mutational patterns in Gag and protease and their possible interactions...
December 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27998269/increased-t-cell-breadth-and-antibody-response-elicited-in-prime-boost-regimen-by-viral-vector-encoded-homologous-siv-gag-env-in-outbred-cd1-mice
#17
Anne-Marie Carola Andersson, Peter Johannes Holst
BACKGROUND: A major obstacle for the development of HIV vaccines is the virus' worldwide sequence diversity. Nevertheless, the presence of T cell epitopes within conserved regions of the virus' structural Gag protein and conserved structures in the envelope (env) sequence raises the possibility that cross-reactive responses may be induced by vaccination. In this study, the aim was to investigate the importance of antigenic match on immunodominance and breadth of obtainable T cell responses...
December 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27997339/toll-like-receptor-3-adjuvant-in-combination-with-virus-like-particles-elicit-a-humoral-response-against-hiv
#18
Ethan Poteet, Phoebe Lewis, Changyi Chen, Sam On Ho, Thai Do, SuMing Chiang, Celia Labranche, David Montefiori, Gary Fujii, Qizhi Yao
Human Immunodeficiency Virus (HIV) Virus-Like Particles (VLPs) composed of HIVIIIB Gag and HIVBaL gp120/gp41 envelope are a pseudovirion vaccine capable of presenting antigens in their native conformations. To enhance the immunogenicity of the HIV Env antigen, VLPs were coupled to VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) containing one of four toll-like-receptor (TLR) ligands, each activating a receptor with distinct cellular localization and downstream pathways. C57BL/6 mice were vaccinated by intranasal prime followed by two sub-cheek boosts and their sera immunoglobulin and neutralizing potency were measured over a duration of 3months after vaccination...
November 21, 2016: Vaccine
https://www.readbyqxmd.com/read/27980506/atomistic-modelling-of-scattering-data-in-the-collaborative-computational-project-for-small-angle-scattering-ccp-sas
#19
Stephen J Perkins, David W Wright, Hailiang Zhang, Emre H Brookes, Jianhan Chen, Thomas C Irving, Susan Krueger, David J Barlow, Karen J Edler, David J Scott, Nicholas J Terrill, Stephen M King, Paul D Butler, Joseph E Curtis
The capabilities of current computer simulations provide a unique opportunity to model small-angle scattering (SAS) data at the atomistic level, and to include other structural constraints ranging from molecular and atomistic energetics to crystallography, electron microscopy and NMR. This extends the capabilities of solution scattering and provides deeper insights into the physics and chemistry of the systems studied. Realizing this potential, however, requires integrating the experimental data with a new generation of modelling software...
December 1, 2016: Journal of Applied Crystallography
https://www.readbyqxmd.com/read/27965093/reversible-aggregation-of-hiv-1-gag-proteins-mediated-by-nucleic-acids
#20
Zhilin Chen, Wei Cheng
HIV-1 Gag protein is the major structural protein for the assembly of virion particles. Although studies have been carried out using partially purified Gag proteins to investigate the mechanisms of viral particle assembly, the outcomes of an assembly reaction remain controversial. Here we have developed an improved procedure for purification of several untagged retroviral Gag proteins from E. coli to more than 95% purity and characterized Gag assembly in solution. We found that HIV-1 Gag proteins can undergo nucleic acid-dependent aggregation with several unexpected features: (1) they form spherical particles that are as large as microns in diameter; (2) the size of the aggregates vary with the molar ratio between nucleic acids and proteins, with the average size of these particles reaching maximal at a molar ratio of 1:2 between nucleic acids and proteins; and (3) these particles can be efficiently disassembled simply upon addition of excess nucleic acids into the solution, suggesting the presence of an ordered assembly...
January 22, 2017: Biochemical and Biophysical Research Communications
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