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https://www.readbyqxmd.com/read/29669829/incomplete-downregulation-of-cd4-expression-affects-hiv-1-env-conformation-and-adcc-responses
#1
Jérémie Prévost, Jonathan Richard, Halima Medjahed, Audrey Alexander, Jennifer Jones, John C Kappes, Christina Ochsenbauer, Andrés Finzi
HIV-1 infected cells expressing envelope glycoproteins (Env) in the CD4-bound conformation on their surface are targeted by antibody-dependent cellular cytotoxicity (ADCC) mediated by CD4-induced (CD4i) antibodies and HIV+ sera. By downregulating the surface expression of CD4, Nef prevents Env-CD4 interaction thus protecting HIV-1-infected cells from ADCC. HIV-1 infectious molecular clones (IMC) are widely used to measure ADCC. In order to facilitate the identification of infected cells and high-throughput ADCC analysis, reporter genes (e...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29664970/correction-a-single-%C3%AE-octyl-glucoside-molecule-induces-hiv-1-nef-dimer-formation-in-the-absence-of-partner-protein-binding
#2
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0192512.].
2018: PloS One
https://www.readbyqxmd.com/read/29652795/counteracting-akt-activation-by-hiv-protease-inhibitors-in-monocytes-macrophages
#3
Sébastien Pasquereau, Amit Kumar, Wasim Abbas, Georges Herbein
Akt signaling plays a central role in many biological processes that are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. The persistence of latent reservoirs in successfully treated patients, mainly located in macrophages and latently infected resting CD4+ T cells, remains a major obstacle in HIV-1 eradication. We assessed the in vitro effects of an HIV protease inhibitor (PI) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) on HIV-1 Nef-induced Akt activation in macrophages and on HIV-1 reactivation in U1 monocytoid cells...
April 13, 2018: Viruses
https://www.readbyqxmd.com/read/29608912/glomerular-mitochondrial-changes-in-hiv-associated-renal-injury
#4
Joseph L Bryant, Poornachander R Guda, Girma Asemu, Rogin Subedi, Sugata Ray, Omar S Khalid, Vivek Shukla, Dhruvil Patel, Harry Davis, Vamshi K C Nimmagadda, Tapas K Makar
HIV-associated nephropathy (HIVAN) is an AIDs-related disease of the kidney. HIVAN is characterized by severe proteinuria, podocyte hyperplasia, collapse, glomerular, and tubulointerstitial damage. HIV-1 transgenic (Tg26) mouse is the most popular model to study the HIV manifestations that develop similar renal presentations as HIVAN. Viral proteins, including Tat, Nef, and Vpr play a significant role in renal cell damage. It has been shown that mitochondrial changes are involved in several kidney diseases, and therefore, mitochondrial dysfunction may be implicated in the pathology of HIVAN...
March 30, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29600767/identification-and-characterization-of-positively-selected-mutations-in-nef-of-four-hiv-1-major-subtypes-from-los-alamos-national-laboratory
#5
Elnaz Shadabi, Binhua Liang, Francis A Plummer, Ma Luo
BACKGROUND: Human immunodeficiency virus-1 (HIV-1) mutates rapidly to escape host immune pressure. This results in the generation of positively selected mutations (PSM) throughout the viral genome. Escape mutations in Nef, one of the accessory proteins of HIV-1, which plays an important role in viral pathogenicity have previously been identified in several large cohort studies, but the evolution of PSMs overtime in various HIV-1 subtypes remains unknown. METHODS: 161 clade A1, 3093 clade B, 647 clade C and 115 clade D HIV-1 nef sequences were obtained from the HIV Database of Los Alamos National Laboratory and aligned using MEGA 6...
March 30, 2018: Current HIV Research
https://www.readbyqxmd.com/read/29588370/intrinsic-properties-and-plasma-membrane-trafficking-route-of-src-family-kinase-sh4-domains-sensitive-to-retargeting-by-hiv-1-nef
#6
Amanda J Chase, Rebecka Wombacher, Oliver T Fackler
The HIV-1 pathogenicity factor Nef enhances viral replication by modulating multiple host cell pathways, including tuning the activation state of infected CD4 T lymphocytes to optimize virus spread. For this, Nef inhibits anterograde transport of the Src family kinase (SFK) Lck toward the plasma membrane (PM). This leads to retargeting of the kinase to the trans-Golgi network (TGN), while the intracellular transport of a related SFK, Fyn, is unaffected by Nef. The 18 amino acid SH4 domain membrane anchor of Lck is necessary and sufficient for Nef-mediated retargeting, but other details of this process are not known...
March 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29559570/uninfected-bystander-cells-impact-the-measurement-of-hiv-specific-antibody-dependent-cellular-cytotoxicity-responses
#7
Jonathan Richard, Jérémie Prévost, Amy E Baxter, Benjamin von Bredow, Shilei Ding, Halima Medjahed, Gloria G Delgado, Nathalie Brassard, Christina M Stürzel, Frank Kirchhoff, Beatrice H Hahn, Matthew S Parsons, Daniel E Kaufmann, David T Evans, Andrés Finzi
The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs)...
March 20, 2018: MBio
https://www.readbyqxmd.com/read/29526437/multilayered-and-versatile-inhibition-of-cellular-antiviral-factors-by-hiv-and-siv-accessory-proteins
#8
REVIEW
Daniel Sauter, Frank Kirchhoff
HIV-1, the main causative agent of AIDS, and related primate lentiviruses show a striking ability to efficiently replicate throughout the lifetime of an infected host. In addition to their high variability, the acquisition of several accessory genes has enabled these viruses to efficiently evade or counteract seemingly strong antiviral immune responses. The respective viral proteins, i.e. Vif, Vpr, Vpu, Vpx and Nef, show a stunning functional diversity, acting by various mechanisms and targeting a large variety of cellular factors involved in innate and adaptive immunity...
February 23, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29518929/upregulation-of-glucose-uptake-and-hexokinase-activity-of-primary-human-cd4-t-cells-in-response-to-infection-with-hiv-1
#9
Maia Kavanagh Williamson, Naomi Coombes, Florian Juszczak, Marios Athanasopoulos, Mariam B Khan, Thomas R Eykyn, Ushani Srenathan, Leonie S Taams, Julianna Dias Zeidler, Andrea T Da Poian, Hendrik Huthoff
Infection of primary CD4+ T cells with HIV-1 coincides with an increase in glycolysis. We investigated the expression of glucose transporters (GLUT) and glycolytic enzymes in human CD4+ T cells in response to infection with HIV-1. We demonstrate the co-expression of GLUT1, GLUT3, GLUT4, and GLUT6 in human CD4+ T cells after activation, and their concerted overexpression in HIV-1 infected cells. The investigation of glycolytic enzymes demonstrated activation-dependent expression of hexokinases HK1 and HK2 in human CD4+ T cells, and a highly significant increase in cellular hexokinase enzyme activity in response to infection with HIV-1...
March 7, 2018: Viruses
https://www.readbyqxmd.com/read/29514909/hiv-1-nef-antagonizes-serinc5-restriction-by-downregulation-of-serinc5-via-the-endosome-lysosome-system
#10
Jing Shi, Ran Xiong, Tao Zhou, Peiyi Su, Xihe Zhang, Xusheng Qiu, Hongmei Li, Sunan Li, Changqing Yu, Bin Wang, Chan Ding, Thomas E Smithgall, Yong-Hui Zheng
The primate lentiviral accessory protein Nef downregulates CD4 and MHC-I from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison with CD4 and MHC-I. We confirm that Nef excludes Ser5 from HIV-1 virions by downregulating its cell surface expression via similar functional motifs required for CD4-downregulation...
March 7, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29463701/bone-degradation-machinery-of-osteoclasts-an-hiv-1-target-that-contributes-to-bone-loss
#11
Brigitte Raynaud-Messina, Lucie Bracq, Maeva Dupont, Shanti Souriant, Shariq M Usmani, Amsha Proag, Karine Pingris, Vanessa Soldan, Christophe Thibault, Florence Capilla, Talal Al Saati, Isabelle Gennero, Pierre Jurdic, Paul Jolicoeur, Jean-Luc Davignon, Thorsten R Mempel, Serge Benichou, Isabelle Maridonneau-Parini, Christel Vérollet
Bone deficits are frequent in HIV-1-infected patients. We report here that osteoclasts, the cells specialized in bone resorption, are infected by HIV-1 in vivo in humanized mice and ex vivo in human joint biopsies. In vitro, infection of human osteoclasts occurs at different stages of osteoclastogenesis via cell-free viruses and, more efficiently, by transfer from infected T cells. HIV-1 infection markedly enhances adhesion and osteolytic activity of human osteoclasts by modifying the structure and function of the sealing zone, the osteoclast-specific bone degradation machinery...
March 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29420192/mechanism-of-stx17-recruitment-to-autophagosomes-via-irgm-and-mammalian-atg8-proteins
#12
Suresh Kumar, Ashish Jain, Farzin Farzam, Jingyue Jia, Yuexi Gu, Seong Won Choi, Michal H Mudd, Aurore Claude-Taupin, Michael J Wester, Keith A Lidke, Tor-Erik Rusten, Vojo Deretic
Autophagy is a conserved eukaryotic process with metabolic, immune, and general homeostatic functions in mammalian cells. Mammalian autophagosomes fuse with lysosomes in a SNARE-driven process that includes syntaxin 17 (Stx17). How Stx17 translocates to autophagosomes is unknown. In this study, we show that the mechanism of Stx17 recruitment to autophagosomes in human cells entails the small guanosine triphosphatase IRGM. Stx17 directly interacts with IRGM, and efficient Stx17 recruitment to autophagosomes requires IRGM...
February 2, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29415006/a-single-%C3%AE-octyl-glucoside-molecule-induces-hiv-1-nef-dimer-formation-in-the-absence-of-partner-protein-binding
#13
Mousheng Wu, John J Alvarado, Corinne E Augelli-Szafran, Roger G Ptak, Thomas E Smithgall
The HIV-1 Nef accessory protein is essential for viral pathogenicity and AIDS progression. Nef forms complexes with multiple host cell factors to facilitate viral replication and promote immune escape of HIV-infected cells. Previous X-ray crystal structures demonstrate that Nef forms homodimers, the orientation of which are influenced by host cell binding partners. In cell-based fluorescence complementation assays, Nef forms homodimers at the plasma membrane. However, recombinant Nef proteins often exist as monomers in solution, suggesting that membrane interaction may also trigger monomer to dimer transitions...
2018: PloS One
https://www.readbyqxmd.com/read/29404888/hiv-1-nef-cawleaq-motif-a-regulator-of-monocytes-invasion-through-eno1-modulation
#14
Reshu Saxena, Umesh Kumar Vekariya, Pradeep Kumar, Amit Kumar Tripathi, Jimut Kanti Ghosh, Raj Kamal Tripathi
HIV-1 transmission and spread involves significant host-virus interaction. Possible targets for obstacle of HIV-1 lie at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and leads their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. For the viral infectivity and pathogenicity, HIV-1 Nef facilitates immune evasion through protein-protein interactions within host cell. HIV-1 Nef is significant for viral infectivity and pathogenicity...
February 5, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29389981/a-high-hiv-1-strain-variability-in-london-uk-revealed-by-full-genome-analysis-results-from-the-iconic-project
#15
Gonzalo Yebra, Dan Frampton, Tiziano Gallo Cassarino, Jade Raffle, Jonathan Hubb, R Bridget Ferns, Laura Waters, C Y William Tong, Zisis Kozlakidis, Andrew Hayward, Paul Kellam, Deenan Pillay, Duncan Clark, Eleni Nastouli, Andrew J Leigh Brown
BACKGROUND & METHODS: The ICONIC project has developed an automated high-throughput pipeline to generate HIV nearly full-length genomes (NFLG, i.e. from gag to nef) from next-generation sequencing (NGS) data. The pipeline was applied to 420 HIV samples collected at University College London Hospitals NHS Trust and Barts Health NHS Trust (London) and sequenced using an Illumina MiSeq at the Wellcome Trust Sanger Institute (Cambridge). Consensus genomes were generated and subtyped using COMET, and unique recombinants were studied with jpHMM and SimPlot...
2018: PloS One
https://www.readbyqxmd.com/read/29386131/a-long-cytoplasmic-loop-governs-the-sensitivity-of-the-anti-viral-host-protein-serinc5-to-hiv-1-nef
#16
Weiwei Dai, Yoshiko Usami, Yuanfei Wu, Heinrich Göttlinger
We recently identified the multipass transmembrane protein SERINC5 as an antiviral protein that can potently inhibit HIV-1 infectivity and is counteracted by HIV-1 Nef. We now report that the anti-HIV-1 activity, but not the sensitivity to Nef, is conserved among vertebrate SERINC5 proteins. However, a Nef-resistant SERINC5 became Nef sensitive when its intracellular loop 4 (ICL4) was replaced by that of Nef-sensitive human SERINC5. Conversely, human SERINC5 became resistant to Nef when its ICL4 was replaced by that of a Nef-resistant SERINC5...
January 23, 2018: Cell Reports
https://www.readbyqxmd.com/read/29364927/viral-protein-nef-is-detected-in-plasma-of-half-of-hiv-infected-adults-with-undetectable-plasma-hiv-rna
#17
Jana Ferdin, Katja Goričar, Vita Dolžan, Ana Plemenitaš, Jeffrey N Martin, Boris M Peterlin, Steven G Deeks, Metka Lenassi
OBJECTIVE: To address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects. DESIGN: We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA) and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort. METHODS: This study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort)...
2018: PloS One
https://www.readbyqxmd.com/read/29338738/rapid-hiv-disease-progression-following-superinfection-in-an-hla-b-27-05-b-57-01-positive-transmission-recipient
#18
Jacqui Brener, Astrid Gall, Jacob Hurst, Rebecca Batorsky, Nora Lavandier, Fabian Chen, Anne Edwards, Chrissy Bolton, Reena Dsouza, Todd Allen, Oliver G Pybus, Paul Kellam, Philippa C Matthews, Philip J R Goulder
BACKGROUND: The factors determining differential HIV disease outcome among individuals expressing protective HLA alleles such as HLA-B*27:05 and HLA-B*57:01 remain unknown. We here analyse two HIV-infected subjects expressing both HLA-B*27:05 and HLA-B*57:01. One subject maintained low-to-undetectable viral loads for more than a decade of follow up. The other progressed to AIDS in < 3 years. RESULTS: The rapid progressor was the recipient within a known transmission pair, enabling virus sequences to be tracked from transmission...
January 16, 2018: Retrovirology
https://www.readbyqxmd.com/read/29334757/high-prevalence-of-non-b-hiv-1-subtypes-in-overseas-sailors-and-prostitutes-in-korea
#19
Young-Keol Cho, Jung-Eun Kim, Brian T Foley
There have been no studies related to groups at the highest risk for HIV-1 infection in Korea before 1993. In this study, for the first time, we report the distribution of HIV subtypes in overseas sailors (OSs) and prostitutes who worked in brothels near U.S. military bases in Korea. We retrospectively determined the sequences of nef in 131 patients using reverse transcription polymerase chain reaction (RT-PCR). These patients composed of 102 OSs, 14 OS spouses, and 15 prostitutes. Phylogenetic analysis was performed using 128 Korean OSs, OS spouses, and prostitutes...
April 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29329537/the-hiv-1-accessory-proteins-nef-and-vpu-downregulate-total-and-cell-surface-cd28-in-cd4-t-cells
#20
Emily N Pawlak, Brennan S Dirk, Rajesh Abraham Jacob, Aaron L Johnson, Jimmy D Dikeakos
BACKGROUND: The HIV-1 accessory proteins Nef and Vpu alter cell surface levels of multiple host proteins to modify the immune response and increase viral persistence. Nef and Vpu can downregulate cell surface levels of the co-stimulatory molecule CD28, however the mechanism of this function has not been completely elucidated. RESULTS: Here, we provide evidence that Nef and Vpu decrease cell surface and total cellular levels of CD28. Moreover, using inhibitors we implicate the cellular degradation machinery in the downregulation of CD28...
January 12, 2018: Retrovirology
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