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https://www.readbyqxmd.com/read/27909244/cd4-down-regulation-by-hiv-1-nef-reveals-distinct-roles-for-%C3%AE-1-and-%C3%AE-2-subunits-of-ap-1-complex-in-protein-trafficking
#1
Lucas A Tavares, Eulália M L da Silva, Mara E da Silva-Januário, Yunan C Januário, Julianne V de Cavalho, Érika S Czernisz, Gonzalo A Mardones, Luis L P daSilva
The HIV accessory protein Nef is a major determinant of viral pathogenesis that facilitates viral particle release, prevents viral antigen presentation and increases infectivity of new virus particles. These functions of Nef involve its ability to remove specific host proteins from the surface of infected cells, including the CD4 receptor. Nef binds to the adaptor protein 2 (AP-2) and CD4 in clathrin-coated pits, forcing CD4 internalization and subsequent target to lysosomes. Herein, we report that this lysosomal targeting requires a variant of the AP-1 comprising the isoform 2 of γ-adaptin...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27894306/first-phase-i-human-clinical-trial-of-a-killed-whole-hiv-1-vaccine-demonstration-of-its-safety-and-enhancement-of-anti-hiv-antibody-responses
#2
Eunsil Choi, Chad J Michalski, Seung Ho Choo, Gyoung Nyoun Kim, Elizabeth Banasikowska, Sangkyun Lee, Kunyu Wu, Hwa-Yong An, Anthony Mills, Stefan Schneider, U Fritz Bredeek, Daniel R Coulston, Shilei Ding, Andrés Finzi, Meijuan Tian, Katja Klein, Eric J Arts, Jamie F S Mann, Yong Gao, C Yong Kang
BACKGROUND: Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus...
November 28, 2016: Retrovirology
https://www.readbyqxmd.com/read/27879338/functional-interplay-between-murine-leukemia-virus-glycogag-serinc5-and-surface-glycoprotein-governs-virus-entry-with-opposite-effects-on-gammaretroviral-and-ebolavirus-glycoproteins
#3
Yadvinder S Ahi, Shu Zhang, Yashna Thappeta, Audrey Denman, Amin Feizpour, Suryaram Gummuluru, Bjoern Reinhard, Delphine Muriaux, Matthew J Fivash, Alan Rein
: Gammaretroviruses, such as murine leukemia viruses (MLVs), encode, in addition to the canonical Gag, Pol, and Env proteins that will form progeny virus particles, a protein called "glycogag" (glycosylated Gag). MLV glycogag contains the entire Gag sequence plus an 88-residue N-terminal extension. It has recently been reported that glycogag, like the Nef protein of HIV-1, counteracts the antiviral effects of the cellular protein Serinc5. We have found, in agreement with prior work, that glycogag strongly enhances the infectivity of MLVs with some Env proteins but not those with others...
November 22, 2016: MBio
https://www.readbyqxmd.com/read/27843096/tnf-and-hiv-1-nef-an-intimate-interplay
#4
Georges Herbein
No abstract text is available yet for this article.
November 9, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27822141/hiv-1-nef-promotes-migration-and-chemokine-synthesis-of-human-basophils-and-mast-cells-through-the-interaction-with-cxcr4
#5
Francesca Wanda Rossi, Nella Prevete, Felice Rivellese, Antonio Lobasso, Filomena Napolitano, Francescopaolo Granata, Carmine Selleri, Amato de Paulis
BACKGROUND: The Nef protein can be detected in plasma of HIV-1-infected patients and plays a role in the pathogenesis of HIV-1. Nef produced during the early stages of infection is fundamental in creating the ideal environment for viral replication, e.g. by reducing the ability of infected cells to induce an immune response. AIM: Based on previous experience showing that both Tat and gp41 of HIV-1 are potent chemotactic factors for basophils and mast cells, and gp120 is a powerful stimulus for the release of histamine and cytokines (IL-4 and IL-13) from basophils, in this study we aimed to verify if the HIV Nef protein can exert some effects on basophils and mast cells purified from healthy volunteers through the interaction with the CXCL12 receptor, CXCR4...
2016: Clinical and Molecular Allergy: CMA
https://www.readbyqxmd.com/read/27803322/s2-from-equine-infectious-anemia-virus-is-an-infectivity-factor-which-counteracts-the-retroviral-inhibitors-serinc5-and-serinc3
#6
Ajit Chande, Emilia Cristiana Cuccurullo, Annachiara Rosa, Serena Ziglio, Susan Carpenter, Massimo Pizzato
The lentivirus equine infectious anemia virus (EIAV) encodes the small protein S2, a pathogenic determinant that is important for virus replication and disease progression in horses. No molecular function had been linked to this accessory protein. We report that S2 can replace the activity of Negative factor (Nef) in HIV-1 infectivity, being required to antagonize the inhibitory activity of Serine incorporator (SERINC) proteins on Nef-defective HIV-1. Like Nef, S2 excludes SERINC5 from virus particles and requires an ExxxLL motif predicted to recruit the clathrin adaptor, Adaptor protein 2 (AP2)...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27798165/hiv-1-nef-impairs-the-formation-of-calcium-membrane-territories-controlling-the-signaling-nanoarchitecture-at-the-immunological-synapse
#7
Joana G Silva, Nuno P Martins, Ricardo Henriques, Helena Soares
The ability of HIV-1 to replicate and to establish long-term reservoirs is strongly influenced by T cell activation. Through the use of membrane-tethered, genetically encoded calcium (Ca(2+)) indicators, we were able to detect for the first time, to our knowledge, the formation of Ca(2+) territories and determine their role in coordinating the functional signaling nanostructure of the synaptic membrane. Consequently, we report a previously unknown immune subversion mechanism involving HIV-1 exploitation, through its Nef accessory protein, of the interconnectivity among three evolutionarily conserved cellular processes: vesicle traffic, signaling compartmentalization, and the second messenger Ca(2+) We found that HIV-1 Nef specifically associates with the traffic regulators MAL and Rab11b compelling the vesicular accumulation of Lck...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27795436/naf1-regulates-hiv-1-latency-by-suppressing-viral-promoter-driven-gene-expression-in-primary-cd4-t-cells
#8
Chuan Li, Hai-Bo Wang, Wen-Dong Kuang, Xiao-Xin Ren, Shu-Ting Song, Huan-Zhang Zhu, Qiang Li, Li-Ran Xu, Hui-Jun Guo, Li Wu, Jian-Hua Wang
: HIV-1 latency is characterized by reversible silencing of viral transcription driven by the long terminal repeat (LTR) promoter of HIV-1. Cellular and viral factors regulating the LTR activity contribute to HIV-1 latency and certain repressive cellular factors modulate viral transcription silencing. Nef-associated factor 1 (Naf1) is a host nucleo-cytoplasmic shuttling protein and regulates multiple cellular signal pathways and HIV-1 production. We have recently reported that the nucleus-located Naf1 promoted nuclear export of unspliced HIV-1 gag mRNA, leading to the accumulated Gag production...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27773542/hiv-nef-and-notch1-dependent-endocytosis-of-adam17-induces-vesicular-tnf-secretion-in-chronic-hiv-infection
#9
Christian Ostalecki, Sebastian Wittki, Jung-Hyun Lee, Miriam M Geist, Nadine Tibroni, Thomas Harrer, Gerold Schuler, Oliver T Fackler, Andreas S Baur
Tumor necrosis factor (TNF) is a key cytokine in HIV replication and pathogenesis. For reasons that are not entirely clear, the cytokine remains upregulated despite anti-retroviral therapy (ART). Here we demonstrate that HIV Nef induces an alternative TNF secretion mechanism that remains active in chronic infection. Ingestion of Nef-containing plasma extracellular vesicles (pEV) from ART patients by primary immune cells, but also Nef expression, induced intracellular proTNF cleavage and secretion of vesicular TNF endosomes...
October 19, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27756485/a-study-of-vaccine-induced-immune-pressure-on-breakthrough-infections-in-the-phambili-phase-2b-hiv-1-vaccine-efficacy-trial
#10
T Hertz, M G Logan, M Rolland, C A Magaret, C Rademeyer, A Fiore-Gartland, P T Edlefsen, A DeCamp, H Ahmed, N Ngandu, B B Larsen, N Frahm, J Marais, R Thebus, D Geraghty, J Hural, L Corey, J Kublin, G Gray, M J McElrath, J I Mullins, P B Gilbert, C Williamson
INTRODUCTION: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. MATERIALS AND METHODS: A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients...
October 15, 2016: Vaccine
https://www.readbyqxmd.com/read/27719633/the-efficiency-of-tat-cell-penetrating-peptide-for-intracellular-uptake-of-hiv-1-nef-expressed-in-e-coli-and-mammalian-cell
#11
Somayeh Kadkhodayan, Azam Bolhassani, Seyed Mehdi Sadat, Shiva Irani, Fatemeh Fotouhi
Cell penetrating peptides (CPPs) or protein transduction domains (PTDs) have been known as a new field in cargo delivery. These peptides such as Tat, Pep-1 and Cady-2 are able to deliver genes and biologically active proteins to cytoplasmic compartments via the plasma membrane. In current study, the efficiency of pEGFP-N1 eukaryotic vector for expression of HIV-1 Tat-Nef fusion was evaluated in HEK-293T cells using TurboFect transfection reagent. In addition, the recombinant GST-Tat-Nef protein was generated in E...
October 6, 2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27685447/changes-in-the-plasticity-of-hiv-1-nef-rna-during-the-evolution-of-the-north-american-epidemic
#12
Amirhossein Manzourolajdad, Mileidy Gonzalez, John L Spouge
Because of a high mutation rate, HIV exists as a viral swarm of many sequence variants evolving under various selective pressures from the human immune system. Although the Nef gene codes for the most immunogenic of HIV accessory proteins, which alone makes it of great interest to HIV research, it also encodes an RNA structure, whose contribution to HIV virulence has been largely unexplored. Nef RNA helps HIV escape RNA interference (RNAi) through nucleotide changes and alternative folding. This study examines Historic and Modern Datasets of patient HIV-1 Nef sequences during the evolution of the North American epidemic for local changes in RNA plasticity...
2016: PloS One
https://www.readbyqxmd.com/read/27681140/the-antagonism-of-hiv-1-nef-to-serinc5-particle-infectivity-restriction-involves-the-counteraction-of-virion-associated-pools-of-the-restriction-factor
#13
Birthe Trautz, Virginia Pierini, Rebecka Wombacher, Bettina Stolp, Amanda J Chase, Massimo Pizzato, Oliver T Fackler
: SERINC3 (serine incorporator 3) and SERINC5 are recently identified host cell inhibitors of HIV-1 particle infectivity that are counteracted by the viral pathogenesis factor Nef. Here we confirm that HIV-1 Nef, but not HIV-1 Vpu, antagonizes the particle infectivity restriction of SERINC5. SERINC5 antagonism occurred in parallel with other Nef activities, including cell surface receptor downregulation, trans-Golgi network targeting of Lck, and inhibition of host cell actin dynamics...
December 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27677160/preclinical-evaluation-of-an-mrna-hiv-vaccine-combining-rationally-selected-antigenic-sequences-and-adjuvant-signals-hti-trimix
#14
Alberto C Guardo, Patrick Tjok Joe, L Miralles, M E Bargalló, B Mothe, A Krasniqi, C Heirman, F García, Kris Thielemans, Christian Brander, Joeri L Aerts, Montserrat Plana
BACKGROUND: The development of a prophylactic vaccine against HIV-1 has so far not been successful. Therefore, attention has shifted more and more towards the development of novel therapeutic vaccines. Here, we evaluated a new mRNA based therapeutic vaccine against HIV-1 encoding activation signals (TriMix: CD40L+CD70+caTLRA4) combined with rationally selected antigenic sequences (HTI sequence: comprised of 16 joined fragments from Gag, Pol, Vif and Nef). METHODS: For this purpose, PBMC from HIV-1-infected individuals on cART, lymph node explants from non-infected humans and splenocytes from immunized mice were collected and several immune functions were measured...
September 24, 2016: AIDS
https://www.readbyqxmd.com/read/27649790/accumulation-of-neutral-lipids-in-liver-and-aorta-of-nef-transgenic-mice
#15
Tatiana Pushkarsky, Evgeny Shilov, Natalya Kruglova, Ronald Naumann, Beda Brichacek, Lucas Jennelle, Dmitri Sviridov, Andrey Kruglov, Sergei Nedospasov, Michael I Bukrinsky
HIV-infected individuals are at high risk of developing atherosclerosis and cardiovascular disease, in part due to HIV-induced impairment of cholesterol metabolism. In vitro studies demonstrated that HIV-1 protein Nef inhibits activity of ABCA1, the main cellular cholesterol transporter, leading to cholesterol accumulation in macrophages and conversion of these cells into foam cells, characteristic for atherosclerosis. However, the mechanisms of Nef-mediated effects on cholesterol metabolism in vivo are not well characterized...
September 21, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27631701/the-potency-of-nef-mediated-serinc5-antagonism-correlates-with-the-prevalence-of-primate-lentiviruses-in-the-wild
#16
Anke Heigele, Dorota Kmiec, Kerstin Regensburger, Simon Langer, Lukas Peiffer, Christina M Stürzel, Daniel Sauter, Martine Peeters, Massimo Pizzato, Gerald H Learn, Beatrice H Hahn, Frank Kirchhoff
The cellular factor serine incorporator 5 (SERINC5) impairs HIV-1 infectivity but is antagonized by the viral Nef protein. We analyzed the anti-SERINC5 activity of Nef proteins across primate lentiviruses and examined whether SERINC5 represents a barrier to cross-species transmissions and/or within-species viral spread. HIV-1, HIV-2, and SIV Nefs counteract human, ape, monkey, and murine SERINC5 orthologs with similar potency. However, HIV-1 Nefs are more active against SERINC5 than HIV-2 Nefs, and chimpanzee SIV (SIVcpz) Nefs are more potent than those of their monkey precursors...
September 14, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27620331/the-effect-of-polyethylene-glycol-modified-lipids-on-the-interaction-of-hiv-1-derived-peptide-dendrimer-complexes-with-lipid-membranes
#17
Sophie Melikishvili, Alexandra Poturnayova, Maksim Ionov, Maria Bryszewska, Tomáš Vary, Julius Cirak, María Ángeles Muñoz-Fernández, Rafael Gomez-Ramirez, Francisco Javier de la Mata, Tibor Hianik
In this study, dendrimers have been purposed as an alternative approach for delivery of HIV peptides to dendritic cells. We have investigated the interaction of dendriplexes formed from polyanionic HIV peptide Nef and cationic carbosilane dendrimer (CBD) with model lipid membranes - large unilamellar vesicles (LUVs), Langmuir monolayers and supported lipid membranes (sBLMs) containing various molar ratio of zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG2000)...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27593341/identification-of-a-novel-hiv-type-1-circulating-recombinant-form-crf86_bc-among-heterosexuals-in-yunnan-china
#18
Yanping Li, Jing Miao, Zhijiang Miao, Yindi Song, Min Wen, Ya Zhang, Shimin Guo, Yuan Zhao, Yue Feng, Xueshan Xia
In recent years, multiple circulating recombinant forms (CRFs) and unique recombinant forms of human immunodeficiency virus type 1 (HIV-1) have been described in Yunnan, China. Here, we identified a novel HIV-1 CRF (CRF86_BC) isolated from three heterosexuals with no obvious epidemiologic linkage in western Yunnan (Baoshan prefecture) in China. CRF86_BC had a subtype C backbone with four subtype B fragments inserted into the pol, vpr, vpu, env, and nef gene regions, respectively. Furthermore, subregion tree analysis revealed that subtype C backbone originated from an Indian C lineage and subtype B segment inserted was from a Thai B lineage...
October 18, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27581991/differential-control-of-bst2-restriction-and-plasmacytoid-dendritic-cell-antiviral-response-by-antagonists-encoded-by-hiv-1-group-m-and-o-strains
#19
Mariana G Bego, Lijun Cong, Katharina Mack, Frank Kirchhoff, Éric A Cohen
: BST2/tetherin is a type I interferon (IFN-I)-stimulated host factor that restricts the release of HIV-1 by entrapping budding virions at the cell surface. This membrane-associated protein can also engage and activate the plasmacytoid dendritic cell (pDC)-specific immunoglobulin-like transcript 7 (ILT7) inhibitory receptor to downregulate the IFN-I response by pDCs. Pandemic HIV-1 group M uses Vpu (M-Vpu) to counteract the two BST2 isoforms (long and short) that are expressed in human cells...
November 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27577610/multi-layered-gag-specific-immunodominant-responses-contribute-to-improved-viral-control-in-the-crf01_ae-subtype-of-hiv-1-infected-msm-subjects
#20
Fanming Jiang, Xiaoxu Han, Hui Zhang, Bin Zhao, Minghui An, Junjie Xu, Zhenxing Chu, Tao Dong, Hong Shang
BACKGROUND: The purpose of this study was to characterize specific cytotoxic T-cell (CTL) responses in men who have sex with men (MSM) subjects infected with the human immunodeficiency virus type 1 (HIV-1) CRF01_AE subtype during the first year of infection and impacts on viral control and evolution. RESULTS: Fifteen HIV-1 primary infected cases were recruited from Liaoning MSM prospective cohort. CTL responses to Gag, Pol and Nef proteins at 3 month and 1 year post infection were detected with Gamma interferon enzyme-linked immunospot (ELISPOT) assay using optimized consensus overlapping peptides, as well as the viral quasispecies sequences from the synchronous plasma...
2016: BMC Immunology
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