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https://www.readbyqxmd.com/read/28179536/hiv-aids-vaccine-candidates-based-on-replication-competent-recombinant-poxvirus-nyvac-c-kc-expressing-trimeric-gp140-and-gag-derived-vlps-or-lacking-the-viral-molecule-b19-that-inhibits-type-i-interferon-activate-relevant-hiv-1-specific-b-and-t-cell-immune
#1
Juan García-Arriaza, Beatriz Perdiguero, Jonathan L Heeney, Michael S Seaman, David C Montefiori, Nicole L Yates, Georgia D Tomaras, Guido Ferrari, Kathryn E Foulds, Mario Roederer, Steven G Self, Bhavesh Borate, Raphael Gottardo, Sanjay Phogat, Jim Tartaglia, Susan W Barnett, Brian Burke, Anthony D Cristillo, Deborah E Weiss, Carter Lee, Karen V Kibler, Bertram L Jacobs, Ralf Wagner, Song Ding, Giuseppe Pantaleo, Mariano Esteban
The non-replicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120), Gag-Pol-Nef antigens (NYVAC-C) showed in phase I clinical trials limited immunogenicity. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4(+) and CD8(+) T cells, here we compared the HIV-1-specific immunogenicity elicited in non-human primates immunized with two replicating NYVAC vectors that have been modified by the insertion of K1L and C7L vaccinia viral host-range genes and express clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC)...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28179429/serinc5-inhibits-hiv-1-fusion-pore-formation-by-promoting-functional-inactivation-of-envelope-glycoproteins
#2
Chetan Sood, Mariana Marin, Ajit Chande, Massimo Pizzato, Gregory B Melikyan
The host proteins, SERINC3 and SERINC5, have been recently shown to incorporate into HIV-1 particles and compromise their ability to fuse with target cells - an effect that is antagonized by the viral Nef protein. Env glycoproteins from different HIV-1 isolates exhibit a broad range of sensitivity to SERINC-mediated restriction, and the mechanism by which SERINCs interfere with HIV-1 fusion remains unclear. Here, we show that incorporation of SERINC5 into virions in the absence of Nef inhibits the formation of small fusion pores between viruses and cells...
February 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28139864/role-of-autophagy-in-hiv-infection-and-pathogenesis
#3
R Nardacci, F Ciccosanti, C Marsella, G Ippolito, M Piacentini, G M Fimia
The aim of autophagy is to re-establish homeostasis in response to a variety of stress conditions. By forming double-membrane vesicles, autophagy engulfs damaged or superfluous cytoplasmic material and recycles degradation products for new synthesis or energy production. Of note, the same mechanism is used to capture pathogens and has important implications in both innate and adaptive immunity. To establish a chronic infection, pathogens have therefore evolved multiple mechanisms to evade autophagy-mediated degradation...
January 31, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28105557/the-anticancer-drug-sunitinib-promotes-autophagyand-protects-from-neurotoxicity-in-an-hiv-1-tat-model-of-neurodegeneration
#4
Jerel A Fields, Jeff Metcalf, Cassia Overk, Anthony Adame, Brian Spencer, Wolfgang Wrasidlo, Jazmin Florio, Edward Rockenstein, Johnny J He, Eliezer Masliah
Despite the success of antiretroviral therapies to control systemic HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HANDs) has not decreased among aging patients with HIV. Autophagy pathway alterations, triggered by HIV-1 proteins including gp120, Tat, and Nef, might contribute to the neurodegenerative process in aging patients with HAND. Although no treatments are currently available to manage HAND, we have previously shown that sunitinib, an anticancer drug that blocks receptor tyrosine-kinase and cyclin kinase pathways, might be of interest...
January 19, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28099189/productive-infection-of-human-neural-progenitor-cells-by-r5-tropic-hiv-1-opiate-co-exposure-heightens-infectivity-and-functional-vulnerability
#5
Joyce M Balinang, Ruturaj R Masvekar, Kurt F Hauser, Pamela E Knapp
OBJECTIVE: Human immunodeficiency virus type-1 (HIV-1) causes a spectrum of CNS complications; many are worsened by opiate co-exposure. Human neural progenitor cells (hNPCs) give rise to all CNS neurons and macroglia. We tested the hypothesis that hNPC maturation and fate are altered by HIV and opiates, contributing to HIV-1-related neuropathology. Since reports that hNPCs are infectable remain controversial, we rigorously examined hNPC infection and ability to propagate infection, and determined whether HIV effects on hNPC function required infection...
January 17, 2017: AIDS
https://www.readbyqxmd.com/read/28091639/gold-nanoparticles-stabilized-by-cationic-carbosilane-dendrons-synthesis-and-biological-properties
#6
Cornelia E Peña-González, Elzbieta Pedziwiatr-Werbicka, Dzmitry Shcharbin, Carlos Guerrero-Beltrán, Viktar Abashkin, Svetlana Loznikova, José L Jiménez, M Ángeles Muñoz-Fernández, Maria Bryszewska, Rafael Gómez, Javier Sánchez-Nieves, F Javier de la Mata
Gold nanoparticles (AuNPs) and polycationic macromolecules are used as gene carriers. Their behaviour is dependent on several factors, such as the size and type of the framework, charge, etc. We have combined both types of systems and prepared AuNPs covered with cationic carbosilane dendrons with the aim to evaluate their biocompatibility. Water soluble dendronized cationic AuNPs were prepared following a straightforward procedure from dendrons, a gold precursor and a reducing agent in water and were characterized by (1)H NMR, transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), ultraviolet spectroscopy (UV), and zeta potential (ZP)...
January 16, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28079886/hiv-1-nef-is-released-in-extracellular-vesicles-derived-from-astrocytes-evidence-for-nef-mediated-neurotoxicity
#7
A Sami Saribas, Stephanie Cicalese, Taha Mohseni Ahooyi, Kamel Khalili, Shohreh Amini, Ilker Kudret Sariyer
Human immunodeficiency virus-associated neurological disorders (HANDs) affect the majority of AIDS patients and are a significant problem among HIV-1-infected individuals who live longer because of combined anti-retroviral therapies. HIV-1 utilizes a number of viral proteins and subsequent cytokine inductions to unleash its toxicity on neurons. Among HIV-1 viral proteins, Nef is a small protein expressed abundantly in astrocytes of HIV-1-infected brains and has been suggested to have a role in the pathogenesis of HAND...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28077653/characterizing-hiv-1-splicing-using-next-generation-sequencing
#8
Ann Emery, Shuntai Zhou, Elizabeth Pollom, Ronald Swanstrom
: Full-length HIV-1 RNA serves as the genome or as an mRNA, or this RNA undergoes splicing using four donors and ten acceptors to create over 50 physiologically relevant transcripts in two size classes (1.8 kb and 4 kb). We developed an assay using Primer ID-tagged deep sequencing to quantify HIV-1 splicing. Using the NL4-3 lab strain we found that A5 (env/nef) is the most commonly used acceptor (about 50%) with A3 (tat) the least used (about 3%). Two small exons are made when a splice to acceptor A1 or A2 is followed by activation of donor D2 or D3, and the high-level use of D2 and D3 dramatically reduces the amount of vif and vpr transcripts...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077643/efficient-vpu-mediated-tetherin-antagonism-by-an-hiv-1-group-o-strain
#9
Katharina Mack, Kathrin Starz, Daniel Sauter, Simon Langer, Frederic Bibollet-Ruche, Gerald H Learn, Christina M Stürzel, Marie Leoz, Jean-Christophe Plantier, Matthias Geyer, Beatrice H Hahn, Frank Kirchhoff
: Simian immunodeficiency viruses (SIVs) use their Nef proteins to counteract the restriction factor tetherin. However, a deletion in human tetherin prevents antagonism by the Nef proteins of SIVcpz and SIVgor, which represent the ape precursors of human immunodeficiency virus type 1 (HIV-1). To promote virus release from infected cells, pandemic HIV-1 group M strains evolved Vpu as tetherin antagonist, while the Nef protein of less widespread HIV-1 group O strains acquired the ability to target a region adjacent to this deletion...
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
#10
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/28076321/secretion-modification-region-derived-peptide-blocks-exosome-release-and-mediates-cell-cycle-arrest-in-breast-cancer-cells
#11
Ming-Bo Huang, Ruben R Gonzalez, James Lillard, Vincent C Bond
PURPOSE: Discovery and development of a novel anticancer PEG-SMR-Clu peptide to prevent breast cancer metastasis. How breast cancer cells and primary mammary epithelial cells interact and communicate with each other to promote tumorigenesis and how to prevent tumor metastasis has long been a concern of researchers. Cancer cells secrete exosomes containing proteins and RNA. These factors can influence tumor development by directly targeting cancer cells and tumor stroma. In this study, we determined the effects of a peptide as an inhibitor of exosome secretion on breast tumors...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28031466/cell-based-fluorescence-complementation-reveals-a-role-for-hiv-1-nef-dimerization-in-ap-2-recruitment-and-cd4-downregulation
#12
Sherry T Shu, Lori A Emert-Sedlak, Thomas E Smithgall
The HIV-1 Nef accessory factor enhances viral infectivity, immune evasion, and AIDS progression. Nef triggers rapid downregulation of CD4 via the endocytic adaptor protein 2 (AP-2) complex, a process linked to enhanced viral infectivity and immune escape. Here we describe a bimolecular fluorescence complementation (BiFC) assay to visualize the interaction of Nef with AP-2 and CD4 in living cells. Interacting protein pairs were fused to complementary, non-fluorescent fragments of YFP and co-expressed in 293T cells...
December 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27998072/effect-of-several-hiv-antigens-simultaneously-loaded-with-g2-nn16-carbosilane-dendrimer-in-the-cell-uptake-and-functionality-of-human-dendritic-cells
#13
Daniel Sepúlveda-Crespo, Enrique Vacas-Córdoba, Valeria Márquez-Miranda, Ingrid Araya-Durán, Rafael Gómez, Francisco Javier de la Mata, Fernando Danilo González-Nilo, Ma Ángeles Muñoz-Fernández
Dendrimers are highly branched, star-shaped, and nanosized polymers that have been proposed as new carriers for specific HIV-1 peptides. Dendritic cells (DCs) are the most-potent antigen-presenting cells that play a major role in the development of cell-mediated immunotherapy due to the generation and regulation of adaptive immune responses against HIV-1. This article reports on the associated behavior of two or three HIV-derived peptides simultaneously (p24/gp160 or p24/gp160/NEF) with cationic carbosilane dendrimer G2-NN16...
December 21, 2016: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/27981421/identification-of-binding-mode-and-prospective-structural-features-of-novel-nef-protein-inhibitors-as-potential-anti-hiv-drugs
#14
Suri Moonsamy, Soumendranath Bhakat, Muthusamy Ramesh, Mahmoud E S Soliman
Human immunodeficiency virus (HIV)-negative factor (Nef) protein is an accessory pathogenic factor, which plays a significant role in acquired immune deficiency syndrome (AIDS). Nef deficient HIV virus took a longer time to progress into AIDS. Therefore, targeting Nef protein is considered as a key strategy towards HIV/AIDS treatment. Up-to-date, only few compounds were reported as Nef inhibitors. This has prompted us to provide a first account of an integrated computational framework in order to identify more potential Nef inhibitors...
December 16, 2016: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27960171/are-basophils-and-mast-cells-masters-in-hiv-infection
#15
Gianni Marone, Gilda Varricchi, Stefania Loffredo, Maria Rosaria Galdiero, Felice Rivellese, Amato de Paulis
The World Health Organization AIDS epidemic update estimates that more than 37 million people are living with HIV infection. Despite the unprecedented success of antiretroviral treatments, significant challenges remain in the fight against HIV. In particular, how uninfected cells capture HIV and transmit virions to target cells remains an unanswered question. Tissue mast cells and peripheral blood basophils can be exposed to virions or HIV products during infection. Several HIV proteins (i.e., envelope glycoproteins gp120 and gp41, Tat, and Nef) can interact with distinct surface receptors expressed by human basophils and mast cells and modulate their functional responses at different levels...
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27928004/effect-of-hiv-1-env-on-serinc5-antagonism
#16
Saina Beitari, Shilei Ding, Qinghua Pan, Andrés Finzi, Chen Liang
: SERINC5 is able to restrict HIV-1 infection by drastically impairing the infectivity of viral particles. Studies have shown that the HIV-1 Nef protein counters SERINC5 through downregulating SERINC5 from the cell surface and preventing the virion incorporation of SERINC5. In addition, the Env proteins of some HIV-1 strains can also overcome SERINC5 inhibition. However, it is unclear how HIV-1 Env does so and why HIV-1 has two mechanisms to resist SERINC5 inhibition. The results of this study show that neither Env nor Nef prevents high levels of ectopic SERINC5 from being incorporated into HIV-1 particles, except that Env, but not Nef, is able to resist inhibition by virion-associated SERINC5...
February 15, 2017: Journal of Virology
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
#17
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
#18
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
#19
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
#20
Georges Herbein
No abstract text is available yet for this article.
November 2016: EBioMedicine
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