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HIV nef

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
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
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
Birthe Trautz, Virginia Pierini, Rebecka Wombacher, Bettina Stolp, Amanda J Chase, Massimo Pizzato, Oliver T Fackler
: SERINC 3 and 5 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 to other Nef activities including cell surface receptor downregulation, trans-Golgi-network targeting of Lck and inhibition of host cell actin dynamics. Interaction motifs with host cell endocytic machinery, Nef-associated kinase complex as well as CD4 cytoplasmic tail/HIV-1 protease were identified as essential Nef determinants for SERINC5 antagonism...
September 28, 2016: Journal of Virology
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
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
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
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)...
September 9, 2016: Biochimica et Biophysica Acta
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
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 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. M-Vpu efficiently downregulates surface long BST2, while it displaces short BST2 molecules away from viral assembly sites...
August 31, 2016: Journal of Virology
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
Andrea Imle, Bettina Stolp, Verena Böhmer, Matthias Geyer, Erez Raz, Oliver T Fackler
The HIV-1 pathogenesis factor Nef interacts with numerous ligands to affect cellular vesicular transport, signal transduction and cytoskeletal dynamics. While most Nef functions depend on multivalent protein interaction motifs, disrupting actin dynamics requires a motif that specifically recruits the host kinase PAK2. An adjacent aspartate was recently predicted to mediate Nef-β-catenin interactions. We report here that β-catenin can be co-immunoprecipitated with Nef.GFP from Jurkat T cell lysates. This association is conserved among lentiviral Nef proteins but does not involve classical Nef protein interaction motifs, including the critical aspartate...
November 2016: Virology
Deeksha Pandey, Avijit Podder, Mansi Pandit, Narayanan Latha
The major causative agent for Acquired Immune Deficiency Syndrome (AIDS) is Human Immunodeficiency Virus-1 (HIV-1). HIV-1 is a predominant subtype of Human Immunodeficiency Virus which counts on human cellular mechanism virtually in every aspect of its life cycle. Binding of viral envelope glycoprotein-gp120 with human cell surface CD4 receptor triggers the early infection stage of HIV-1. This study focuses on the interaction interface between these two proteins that play a crucial role for viral infectivity...
August 21, 2016: Journal of Biomolecular Structure & Dynamics
Dorota Kmiec, Shilpa S Iyer, Christina M Stürzel, Daniel Sauter, Beatrice H Hahn, Frank Kirchhoff
UNLABELLED: Human immunodeficiency virus type 1 (HIV-1) groups M, N, O, and P are the result of independent zoonotic transmissions of simian immunodeficiency viruses (SIVs) infecting great apes in Africa. Among these, only Vpu proteins of pandemic HIV-1 group M strains evolved potent activity against the restriction factor tetherin, which inhibits virus release from infected cells. Thus, effective Vpu-mediated tetherin antagonism may have been a prerequisite for the global spread of HIV-1...
2016: MBio
Matthew Pace, James Williams, Ayako Kurioka, Andrew B Gerry, Bent Jakobsen, Paul Klenerman, Nneka Nwokolo, Julie Fox, Sarah Fidler, John Frater
In the search for a cure for HIV-1 infection, histone deacetylase inhibitors (HDACi) are being investigated as activators of latently infected CD4 T cells to promote their targeting by cytotoxic T-lymphocytes (CTL). However, HDACi may also inhibit CTL function, suggesting different immunotherapy approaches may need to be explored. Here, we study the impact of different HDACi on both Natural Killer (NK) and CTL targeting of HIV-1 infected cells. We found HDACi down-regulated HLA class I expression independently of HIV-1 Nef which, without significantly compromising CTL function, led to enhanced targeting by NK cells...
August 2016: PLoS Pathogens
Dürdal Us
Superantigens (SAgs) are microbial proteins produced by various microorganisms that elicit excessive and strong stimulation of T cells via an unconventional mechanism. They cause polyclonal activation of T cells in a non-specific manner, by binding to a particular variable-beta (Vβ) chain of T-cell receptor (TCR) and MHC class II molecule, in unprocessed form and outside of peptide-binding cleft, forming a bridge between the antigen presenting cell and the T cell. SAgs are classified into three groups, namely 1) exogenous (soluble proteins and exotoxins secreted by microorganisms), 2) endogenous (transmembrane proteins encoded by viruses which are integrated into the genome) and 3) B-cell SAgs (proteins which stimulate predominantly B cells)...
July 2016: Mikrobiyoloji Bülteni
Joseph S Murray, Elaina H Murray
Genes of the major histocompatibility complex (MHC; also called HLA in human) are polymorphic elements in the genomes of sharks to humans. Class-I and class-II MHC loci appear responsible for much of the genetic linkage to myriad disease states via the capacity to bind short (~8-15 a.a.) peptides of a given pathogen's proteome, or in some cases, the altered proteomes of cancerous cells, and even (in autoimmunity) certain nominal 'self' peptides (Janeway, 2004).(1) Unfortunately, little is known about how the canonical structure of the MHC-I/-II peptide-presenting gene evolved, particularly since beyond ~500 Mya (sharks) no paralogs exist...
May 2016: Mobile Genetic Elements
Ruth Hunegnaw, Marina Vassylyeva, Larisa Dubrovsky, Tatiana Pushkarsky, Dmitri Sviridov, Anastasia A Anashkina, Aykut Üren, Beda Brichacek, Dmitry G Vassylyev, Alexei A Adzhubei, Michael Bukrinsky
OBJECTIVE: HIV-infected patients are at an increased risk of developing atherosclerosis, in part because of downmodulation and functional impairment of ATP-binding cassette A1 (ABCA1) cholesterol transporter by the HIV-1 protein Nef. The mechanism of this effect involves Nef interacting with an ER chaperone calnexin and disrupting calnexin binding to ABCA1, leading to ABCA1 retention in ER, its degradation and resulting suppression of cholesterol efflux. However, molecular details of Nef-calnexin interaction remained unknown, limiting the translational impact of this finding...
September 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Rebecca Rose, Susanna L Lamers, David J Nolan, Ekaterina Maidji, N R Faria, Oliver G Pybus, James J Dollar, Samuel A Maruniak, Andrew C McAvoy, Marco Salemi, Cheryl A Stoddart, Elyse J Singer, Michael S McGrath
UNLABELLED: While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses...
October 15, 2016: Journal of Virology
Dohun Pyeon, Khalid Amine Timani, Fahad Gulraiz, Johnny J He, In-Woo Park
HIV-1 Nef is necessary and may be sufficient for HIV-1-associated AIDS pathogenicity, in that knockout of Nef alone can protect HIV-infected patients from AIDS. We therefore investigated the feasibility of physical knockout of Nef, using the host ubiquitin proteasome system in HIV-1-infected cells. Our co-immunoprecipitation analysis demonstrated that Nef interacted with ubiquitin specific protease 15 (USP15), and that USP15, which is known to stabilize cellular proteins, degraded Nef. Nef could also cause decay of USP15, although Nef-mediated degradation of USP15 was weaker than USP15-mediated Nef degradation...
September 2, 2016: Virus Research
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