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https://www.readbyqxmd.com/read/29150603/bacterially-derived-synthetic-mimetics-of-mammalian-oligomannose-prime-antibody-responses-that-neutralize-hiv-infectivity
#1
Ralph Pantophlet, Nino Trattnig, Sasha Murrell, Naiomi Lu, Dennis Chau, Caitlin Rempel, Ian A Wilson, Paul Kosma
Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29149197/sieve-analysis-of-breakthrough-hiv-1-sequences-in-hvtn-505-identifies-vaccine-pressure-targeting-the-cd4-binding-site-of-env-gp120
#2
Allan C deCamp, Morgane Rolland, Paul T Edlefsen, Eric Sanders-Buell, Breana Hall, Craig A Magaret, Andrew J Fiore-Gartland, Michal Juraska, Lindsay N Carpp, Shelly T Karuna, Meera Bose, Steven LePore, Shana Miller, Annemarie O'Sullivan, Kultida Poltavee, Hongjun Bai, Kalpana Dommaraju, Hong Zhao, Kim Wong, Lennie Chen, Hasan Ahmed, Derrick Goodman, Matthew Z Tay, Raphael Gottardo, Richard A Koup, Robert Bailer, John R Mascola, Barney S Graham, Mario Roederer, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Elizabeth Adams, Patricia D'Souza, James Kublin, Lawrence Corey, Daniel E Geraghty, Nicole Frahm, Georgia D Tomaras, M Juliana McElrath, Lisa Frenkel, Sheila Styrchak, Sodsai Tovanabutra, Magdalena E Sobieszczyk, Scott M Hammer, Jerome H Kim, James I Mullins, Peter B Gilbert
Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120)...
2017: PloS One
https://www.readbyqxmd.com/read/29147885/proceedings-of-the-2017-isev-symposium-on-hiv-neurohiv-drug-abuse-evs
#3
Guoku Hu, Sowmya Yelamanchili, Fatah Kashanchi, Norman Haughey, Vincent C Bond, Kenneth W Witwer, Lynn Pulliam, Shilpa Buch
Despite the success of combination antiretroviral therapy (cART), there is increased prevalence of HIV-associated neurocognitive disorders (HAND) in HIV-1-infected individuals on cART, which poses a major health care challenge. Adding further complexity to this long-term antiretroviral use is the comorbidity with drugs of abuse such as morphine, cocaine, and methamphetamine, which can in turn, exacerbate neurologic and cognitive deficits associated with HAND. Furthermore, HIV proteins, such as the transactivator of transcription (Tat) and the envelope protein (gp120), as well as antiretrovirals themselves can also contribute to the progression of neurodegeneration underlying HAND...
November 16, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29132227/oxidative-stress-in-hiv-infection-and-alcohol-use-role-of-redox-signals-in-modulation-of-lipid-rafts-and-abc-transporters
#4
Samikkannu Thangavel, Carmen T Mulet, Venkata S R Atluri, Marisela Agudelo, Rhonda Rosenberg, Jessy G Devieux, Madhavan P N Nair
AIMS: HIV infection induces oxidative stress and alcohol use accelerates disease progression subsequently causing immune dysfunction. However, HIV and alcohol impact on lipid rafts-mediated immune dysfunction remains unknown. In this study, we investigate the modulation by which oxidative stress induces reactive oxygen species (ROS) affecting redox expression, lipid rafts caveiloin-1, ATP-binding cassette (ABC)-transporters, and transcriptional SREBP gene and protein modification and how these mechanisms are associated with arachidonic acid (AA) metabolites in HIV positive alcohol users, and how they escalate immune dysfunction...
November 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29129698/evaluation-of-different-parameters-of-humoral-and-cellular-immune-responses-in-hiv-serodiscordant-heterosexual-couples-humoral-response-potentially-implicated-in-modulating-transmission-rates
#5
María Julia Ruiz, Jimena Salido, Lorena Abusamra, Yanina Ghiglione, Cintia Cevallos, Gabriel Damilano, Ana María Rodriguez, César Trifone, Natalia Laufer, Luis D Giavedoni, Omar Sued, Horacio Salomón, María Magdalena Gherardi, Gabriela Turk
As the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC) represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC) activity were assessed in nine HIV-exposed seronegative individuals (ESN) and their corresponding HIV seropositive partners (HIV(+)-P), in eighteen chronically infected HIV subjects (C), nine chronically infected subjects known to be HIV transmitters (CT) and ten healthy HIV(-) donors (HD)...
November 3, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29121497/mannosylcalix-n-arenes-as-multivalent-ligands-for-dc-sign
#6
Ilaria Morbioli, Vanessa Porkolab, Andrea Magini, Alessandro Casnati, Franck Fieschi, Francesco Sansone
DC-SIGN is a receptor protruded from the membrane of immature dendritic cells (DCs) that participates in the activation of the immune response through the recognition of pathogen-associated molecular patterns (PAMPs). On the other hand, HIV exploits the interaction between high-mannose structures of its envelope glycoprotein gp120 and DC-SIGN to be transported towards and infect T-cells. DC-SIGN is involved in the recognition process in the form of a tetramer and the multiple exposition of carbohydrate recognition sites (CRSs) is amplified by the formation on the DCs membrane of patches of tetramers...
October 31, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/29119112/expression-and-immunogenicity-of-two-recombinant-fusion-proteins-comprising-foot-and-mouth-disease-virus-structural-protein-vp1-and-dc-sign-binding-glycoproteins
#7
Xinsheng Liu, Jianliang Lv, Yuzhen Fang, Peng Zhou, Yanzhen Lu, Li Pan, Zhongwang Zhang, Junwu Ma, Yongguang Zhang, Yonglu Wang
Improving vaccine immunogenicity by targeting antigens to dendritic cells has recently emerged as a new design strategy in vaccine development. In this study, the VP1 gene of foot-and-mouth disease virus (FMDV) serotype A was fused with the gene encoding human immunodeficiency virus (HIV) membrane glycoprotein gp120 or C2-V3 domain of hepatitis C virus (HCV) envelope glycoprotein E2, both of which are DC-SIGN-binding glycoproteins. After codon optimization, the VP1 protein and the two recombinant VP1-gp120 and VP1-E2 fusion proteins were expressed in Sf9 insect cells using the insect cell-baculovirus expression system...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29114997/in-vitro-modeling-of-hiv-proviral-activity-in-microglia
#8
Lee A Campbell, Christopher T Richie, Yajun Zhang, Emily J Heathward, Lamarque M Coke, Emily Y Park, Brandon K Harvey
Microglia, the resident macrophages of the brain, play a key role in the pathogenesis of HIV-associated neurocognitive disorders (HAND) due to their productive infection by HIV. This results in the release of neurotoxic viral proteins and pro-inflammatory compounds which negatively affect the functionality of surrounding neurons. Because models of HIV infection within the brain are limited, we aimed to create a novel microglia cell line with an integrated HIV provirus capable of recreating several hallmarks of HIV infection...
November 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29111178/dose-dependent-neurocognitive-deficits-following-postnatal-day-10-hiv-1-viral-protein-exposure-relationship-to-hippocampal-anatomy-parameters
#9
Sylvia Fitting, Kristen A McLaurin, Rosemarie M Booze, Charles F Mactutus
Despite the availability of antiretroviral prophylactic treatment, pediatric human immunodeficiency virus type 1 (HIV-1) continues to be a significant risk factor in the post-cART era. The time of infection (i.e., during pregnancy, delivery or breastfeeding) may play a role in the development of neurocognitive deficits in pediatric HIV-1. HIV-1 viral protein exposure on postnatal day (P)1, preceding the postnatal brain growth spurt in rats, had deleterious effects on neurocognitive development and anatomical parameters of the hippocampus (Fitting et al...
October 27, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/29093081/analysis-of-select-hsv-1-proteins-for-restriction-of-human-immunodeficiency-virus-type-1-the-hsv-1-gm-protein-potently-restricts-hiv-1-by-preventing-the-intracellular-transport-and-processing-of-env-gp160
#10
Sachith Polpitiya Arachchige, Wyatt Henke, Ankita Pramanik, Maria Kalamvoki, Edward B Stephens
Proteins encoded by viruses that impair or shutdown specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus type 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M (gM), US3 and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference of the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29075998/transgenic-mice-expressing-hiv-1-envelope-protein-gp120-in-the-brain-as-an-animal-model-in-neuroaids-research
#11
Victoria E Thaney, Ana B Sanchez, Jerel A Fields, Arpi Minassian, Jared W Young, Ricky Maung, Marcus Kaul
HIV-1 infection causes injury to the central nervous system (CNS) and is often associated with neurocognitive disorders. One model for brain damage seen in AIDS patients is the transgenic (tg) mouse expressing a soluble envelope protein gp120 of HIV-1 LAV in the brain in astrocytes under the control of the promoter of glial fibrillary acidic protein. These GFAP-gp120tg mice manifest several key neuropathological features observed in AIDS brains, such as decreased synaptic and dendritic density, increased numbers of activated microglia, and pronounced astrocytosis...
October 26, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29065142/safety-and-vaccine-induced-hiv-1-immune-responses-in-healthy-volunteers-following-a-late-mva-b-boost-4-years-after-the-last-immunization
#12
RANDOMIZED CONTROLLED TRIAL
Alberto C Guardo, Carmen Elena Gómez, Vicens Díaz-Brito, Judit Pich, Joan Albert Arnaiz, Beatriz Perdiguero, Juan García-Arriaza, Nuria González, Carlos O S Sorzano, Laura Jiménez, José Luis Jiménez, María Ángeles Muñoz-Fernández, José M Gatell, José Alcamí, Mariano Esteban, Juan Carlos López Bernaldo de Quirós, Felipe García, Montserrat Plana
BACKGROUND: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. METHODS: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization...
2017: PloS One
https://www.readbyqxmd.com/read/29061509/monoacylglycerol-lipase-inhibitor-jzl184-prevents-hiv-1-gp120-induced-synapse-loss-by-altering-endocannabinoid-signaling
#13
Xinwen Zhang, Stanley A Thayer
Monoacylglycerol lipase (MGL) hydrolyzes 2-arachidonoylglycerol to arachidonic acid and glycerol. Inhibition of MGL may attenuate neuroinflammation by enhancing endocannabinoid signaling and decreasing prostaglandin (PG) production. Almost half of HIV infected individuals are afflicted with HIV-associated neurocognitive disorder (HAND), a neuroinflammatory disease in which cognitive decline correlates with synapse loss. HIV infected cells shed the envelope protein gp120 which is a potent neurotoxin that induces synapse loss...
October 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29056481/targeting-the-late-stage-of-hiv-1-entry-for-antibody-dependent-cellular-cytotoxicity-structural-basis-for-env-epitopes-in-the-c11-region
#14
William D Tolbert, Neelakshi Gohain, Nirmin Alsahafi, Verna Van, Chiara Orlandi, Shilei Ding, Loïc Martin, Andrés Finzi, George K Lewis, Krishanu Ray, Marzena Pazgier
Antibodies can have an impact on HIV-1 infection in multiple ways, including antibody-dependent cellular cytotoxicity (ADCC), a correlate of protection observed in the RV144 vaccine trial. One of the most potent ADCC-inducing epitopes on HIV-1 Env is recognized by the C11 antibody. Here, we present the crystal structure, at 2.9 Å resolution, of the C11-like antibody N12-i3, in a quaternary complex with the HIV-1 gp120, a CD4-mimicking peptide M48U1, and an A32-like antibody, N5-i5. Antibody N12-i3 recognizes an epitope centered on the N-terminal "eighth strand" of a critical β sandwich, which our analysis indicates to be emblematic of a late-entry state, after the gp120 detachment...
November 7, 2017: Structure
https://www.readbyqxmd.com/read/29051495/the-%C3%AE-20-%C3%AE-21-of-gp120-is-a-regulatory-switch-for-hiv-1-env-conformational-transitions
#15
Alon Herschhorn, Christopher Gu, Francesca Moraca, Xiaochu Ma, Mark Farrell, Amos B Smith, Marie Pancera, Peter D Kwong, Arne Schön, Ernesto Freire, Cameron Abrams, Scott C Blanchard, Walther Mothes, Joseph G Sodroski
The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally "closed" State 1 to more "open" conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29049306/protein-structural-disorder-of-the-envelope-v3-loop-contributes-to-the-switch-in-human-immunodeficiency-virus-type-1-cell-tropism
#16
Xiaowei Jiang, Felix Feyertag, David L Robertson
Human immunodeficiency virus type 1 (HIV-1) envelope gp120 is partly an intrinsically disordered (unstructured/disordered) protein as it contains regions that do not fold into well-defined protein structures. These disordered regions play important roles in HIV's life cycle, particularly, V3 loop-dependent cell entry, which determines how the virus uses two coreceptors on immune cells, the chemokine receptors CCR5 (R5), CXCR4 (X4) or both (R5X4 virus). Most infecting HIV-1 variants utilise CCR5, while a switch to CXCR4-use occurs in the majority of infections...
2017: PloS One
https://www.readbyqxmd.com/read/29046160/construction-and-production-of-hiv-vlp-harboring-mper-v3-for-potential-vaccine-study
#17
Tohidi Fatemeh, Sadat Seyed Mehdi, Bolhassani Azam, Yaghobi Ramin
Vaccine against HIV-1 is not currently available. In present, Virus like particles (VLPs) as effective strategy was used in several vaccine developing. Two conserved sequences; V3 loop of gp120 and the membrane-proximal external region (MPER) of gp41 are dominant sites for vaccine studies. In this study, we used fusion gene of MPER and V3 to product recombinant VLPs and introduced a novel retroviral VLPs harboring high copy of MPER-V3 for HIV-1 vaccine design. The pEGFP-N1 plasmid harboring MPER-V3 sequence with Vpr linker was constructed...
October 17, 2017: Current HIV Research
https://www.readbyqxmd.com/read/29045410/patterns-and-rates-of-viral-evolution-in-hiv-1-subtype-b-infected-females-and-males
#18
Michael J Dapp, Kord M Kober, Lennie Chen, Dylan H Westfall, Kim Wong, Hong Zhao, Breana M Hall, Wenjie Deng, Thomas Sibley, Suvankar Ghorai, Katie Kim, Natalie Chen, Sarah McHugh, Lily Au, Mardge Cohen, Kathryn Anastos, James I Mullins
Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS. However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men. We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)...
2017: PloS One
https://www.readbyqxmd.com/read/29031113/cross-sectional-and-longitudinal-small-animal-pet-shows-pre-and-post-synaptic-striatal-dopaminergic-deficits-in-an-animal-model-of-hiv
#19
Sanhita Sinharay, Dianne Lee, Swati Shah, Siva Muthusamy, Georgios Z Papadakis, Xiang Zhang, Dragan Maric, William C Reid, Dima A Hammoud
INTRODUCTION: In vivo imaging biomarkers of various HIV neuropathologies, including dopaminergic dysfunction, are still lacking. Towards developing dopaminergic biomarkers of brain involvement in HIV, we assessed the pre and postsynaptic components of the dopaminergic system in the HIV-1 transgenic rat (Tg), a well-characterized model of treated HIV+ patients, using small-animal PET imaging. METHODS: Fifteen to 18 month-old Tg and wild type (WT) rats were imaged with both [18F]-FP-CMT, a dopamine transporter (DAT) ligand (n=16), and [18F]-Fallypride, a D2/D3 dopamine receptor (D2/D3DR) ligand (n=16)...
August 31, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29021402/hiv-exposed-infants-vaccinated-with-a-mf59-rgp120-vaccine-have-higher-magnitude-anti-v1v2-igg-responses-than-adults-immunized-with-the-same-vaccine
#20
Erin P McGuire, Youyi Fong, Christopher Toote, Coleen K Cunningham, Elizabeth J McFarland, William Borkowsky, Susan Barnett, Hannah L Itell, Amit Kumar, Glenda Gray, M Julianna McElrath, Georgia D Tomaras, Sallie R Permar, Genevieve G Fouda
In the RV144 vaccine trial, IgG responses against the HIV envelope variable loops 1 and 2 (V1V2) were associated with decreased HIV acquisition risk. We previously reported that infants immunized with a MF59 adjuvanted rgp120 vaccine developed higher magnitude anti-V1V2 IgG responses than adult RV144 vaccinees. To determine if the robust antibody response in infants is due to differences in vaccine regimens or to inherent differences between the adult and infant immune systems, we compared Env-specific IgG responses in adults and infants immunized with the same MF59 and Alum adjuvanted HIV envelope vaccines...
October 11, 2017: Journal of Virology
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