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https://www.readbyqxmd.com/read/28218750/quaternary-contact-in-the-initial-interaction-of-cd4-with-the-hiv-1-envelope-trimer
#1
Qingbo Liu, Priyamvada Acharya, Michael A Dolan, Peng Zhang, Christina Guzzo, Jacky Lu, Alice Kwon, Deepali Gururani, Huiyi Miao, Tatsiana Bylund, Gwo-Yu Chuang, Aliaksandr Druz, Tongqing Zhou, William J Rice, Christoph Wigge, Bridget Carragher, Clinton S Potter, Peter D Kwong, Paolo Lusso
Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial receptor interaction has been difficult to study because of major CD4-induced structural rearrangements. Here we used cryogenic electron microscopy (cryo-EM) to visualize the initial contact of CD4 with the HIV-1 Env trimer at 6.8-Å resolution. A single CD4 molecule is embraced by a quaternary HIV-1-Env surface formed by coalescence of the previously defined CD4-contact region with a second CD4-binding site (CD4-BS2) in the inner domain of a neighboring gp120 protomer...
February 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28213534/quantitative-correlation-between-infectivity-and-gp120-density-on-hiv-1-virions-revealed-by-optical-trapping-virometry
#2
Michael C DeSantis, Jin H Kim, Hanna Song, Per Johan Klasse, Wei Cheng
No abstract text is available yet for this article.
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28209172/evaluation-of-the-contribution-of-the-transmembrane-region-to-the-ectodomain-conformation-of-the-human-immunodeficiency-virus-hiv-1-envelope-glycoprotein
#3
Hanh T Nguyen, Navid Madani, Haitao Ding, Emerald Elder, Amy Princiotto, Christopher Gu, Patrice Darby, James Alin, Alon Herschhorn, John C Kappes, Youdong Mao, Joseph G Sodroski
BACKGROUND: The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env), a Type 1 transmembrane protein, assembles into a trimeric spike complex that mediates virus entry into host cells. The high potential energy of the metastable, unliganded Env trimer is maintained by multiple non-covalent contacts among the gp120 exterior and gp41 transmembrane Env subunits. Structural studies suggest that the gp41 transmembrane region forms a left-handed coiled coil that contributes to the Env trimer interprotomer contacts...
February 16, 2017: Virology Journal
https://www.readbyqxmd.com/read/28207487/antibody-mediated-immune-exclusion-of-hiv
#4
Ruth M Ruprecht, Samir K Lakhashe
PURPOSE OF REVIEW: Although approximately 90% of all HIV transmissions in humans occur through mucosal contact, the induction of mucosal anti-HIV immune responses has remained understudied. Here we summarize data demonstrating the powerful protection that is achievable at mucosal frontlines through virus-specific mucosal IgA alone or combined with IgG. RECENT FINDINGS: Passive immunization with different monoclonal antibody subclasses but identical epitope specificity (the conserved V3-loop crown of HIV gp120) has revealed that the dimeric IgA1 (dIgA1) form with its open hinge can prevent simian-human immunodeficiency virus (SHIV) acquisition in rhesus macaques at a higher rate than dIgA2...
February 15, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28202756/a-glycosylation-benchmark-profile-for-hiv-1-envelope-glycoprotein-production-based-on-eleven-env-trimers
#5
Eden P Go, Haitao Ding, Shijian Zhang, Rajesh P Ringe, Nathan Nicely, David Hua, Robert T Steinbock, Michael Golabek, James Alin, S Munir Alam, Albert Cupo, Barton F Haynes, John C Kappes, John P Moore, Joseph G Sodroski, Heather Desaire
HIV-1 envelope glycoprotein (Env) glycosylation is important because individual glycans are components of multiple broadly neutralizing antibody epitopes, while shielding other sites that might otherwise be immunogenic. The glycosylation on Env is influenced by a variety of factors, including the genotype of the protein, the cell line used for its expression, and the details of the construct design. Here, we used a mass spectrometry-based approach to map the complete glycosylation profile at every site in multiple HIV-1 Env trimers, accomplishing two goals: 1) We determined which glycosylation sites contain conserved glycan profiles across many trimeric Envs...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28185743/differential-induction-of-anti-v3-crown-antibodies-with-cradle-and-ladle-binding-modes-in-response-to-hiv-1-envelope-vaccination
#6
Preetha Balasubramanian, Rajnish Kumar, Constance Williams, Vincenza Itri, Shixia Wang, Shan Lu, Ann J Hessell, Nancy L Haigwood, Faruk Sinangil, Keith W Higgins, Lily Liu, Liuzhe Li, Phillipe Nyambi, Miroslaw K Gorny, Maxim Totrov, Arthur Nadas, Xiang-Peng Kong, Susan Zolla-Pazner, Catarina E Hioe
The V3 loop in the HIV envelope gp120 is one of the immunogenic sites targeted by Abs. The V3 crown in particular has conserved structural elements recognized by cross-reactive neutralizing Abs, indicating its potential contribution in protection against HIV. Crystallographic analyses of anti-V3 crown mAbs in complex with the V3 peptides have revealed that these mAbs recognize the conserved sites on the V3 crown via two distinct strategies: a cradle-binding mode (V3C) and a ladle-binding (V3L) mode. However, almost all of the anti-V3 crown mAbs studied in the past were isolated from chronically HIV-infected individuals...
February 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28181540/hiv-related-proteins-prolong-macrophage-survival-through-induction-of-triggering-receptor-expressed-on-myeloid-cells-1
#7
Zhihong Yuan, Xian Fan, Bashar Staitieh, Chetna Bedi, Paul Spearman, David M Guidot, Ruxana T Sadikot
Triggering receptor expressed on myeloid cells-1(TREM-1) is a member of the superimmunoglobulin receptor family. We have previously shown that TREM-1 prolongs survival of macrophages treated with lipoolysaccharide through Egr2-Bcl2 signaling. Recent studies suggest a role for TREM-1 in viral immunity. Human immunodeficiency virus-1 (HIV) targets the monocyte/macrophage lineage at varying stages of infection. Emerging data suggest that macrophages are key reservoirs for latent HIV even in individuals on antiretroviral therapy...
February 9, 2017: Scientific Reports
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
#8
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/28178146/pairwise-diversity-and-tmrca-as-potential-markers-for-hiv-infection-recency
#9
Sikhulile Moyo, Eduan Wilkinson, Alain Vandormael, Rui Wang, Jia Weng, Kenanao P Kotokwe, Simani Gaseitsiwe, Rosemary Musonda, Joseph Makhema, Max Essex, Susan Engelbrecht, Tulio de Oliveira, Vladimir Novitsky
Intrahost human immunodeficiency virus (HIV)-1 diversity increases linearly over time. We assessed the extent to which mean pairwise distances and the time to the most recent common ancestor (tMRCA) inferred from intrahost HIV-1C env sequences were associated with the estimated time of HIV infection. Data from a primary HIV-1C infection study in Botswana were used for this analysis (N = 42). A total of 2540 HIV-1C env gp120 variable loop region 1 to conserved region 5 (V1C5) of the HIV-1 envelope gp120 viral sequences were generated by single genome amplification and sequencing, with an average of 61 viral sequences per participant and 11 sequences per time point per participant...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28177967/the-neutralizing-and-targeting-properties-of-a-new-set-of-%C3%AE-4%C3%AE-7-specific-antibodies-are-influenced-by-their-isotype
#10
Alexandre Girard, Katija Jelicic, Don Van Ryk, Nicolas Rochereau, Claudia Cicala, James Arthos, Christian Genin, Bernard Verrier, Stephanie Laurant, Diane Razanajaoana-Doll, Pin Jean-Jacques, Stéphane Paul
The homing of lymphocytes to mucosa is mainly controlled by α4β7 integrin, and it is amplified during gut chronic inflammation, as occurs with HIV and/or Inflammatory Bowel Diseases. We designed and applied an improved immunization strategy based on an innovative selection process to isolate new α4β7 lymphocyte-specific mAbs that are able to prevent their migration into inflamed gut tissues and/or to counteract HIV infection in vitro. Firstly, five mAbs (one IgA, one IgM, and four IgGs) were selected based on their capacity to recognize α4 or β7 homodimers and α4β7 heterodimers in transfected human cells...
February 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28161890/homology-guided-mutational-analysis-reveals-the-functional-requirements-for-antinociceptive-specificity-of-crmp2-derived-peptides
#11
Aubin Moutal, Wennan Li, Yue Wang, Weina Ju, Shizhen Luo, Song Cai, Liberty François-Moutal, Samantha Perez-Miller, Jackie Hu, Erik T Dustrude, Todd W Vanderah, Vijay Gokhale, May Khanna, Rajesh Khanna
BACKGROUND AND PURPOSE: N-type voltage-gated calcium (CaV2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Despite CaV2.2 antagonism being recommended as first-line treatment for neuropathic pain, calcium-current blocking gabapentinoids inadequately alleviate chronic pain symptoms and are often mired by numerous side-effects. Collapsin response mediator protein 2 (CRMP2) targets CaV2.2 to the sensory neuron membrane, and allosterically modulates Cav2...
February 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28151945/antigenic-characterization-of-the-human-immunodeficiency-virus-hiv-1-envelope-glycoprotein-precursor-incorporated-into-nanodiscs
#12
Kristen C Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C Kappes, Joseph Sodroski
The entry of human immunodeficiency virus (HIV-1) into host cells is mediated by the viral envelope glycoproteins (Envs), which are derived by the proteolytic cleavage of a trimeric gp160 Env precursor. The mature Env trimer is a major target for entry inhibitors and vaccine-induced neutralizing antibodies. Env interstrain variability, conformational flexibility and heavy glycosylation contribute to evasion of the host immune response, and create challenges for structural characterization and vaccine development...
2017: PloS One
https://www.readbyqxmd.com/read/28137224/sulfated-glycans-in-hiv-infection-and-therapy
#13
Vitor H Pomin, Francisco F Bezerra, Paulo A G Soares
The human immunodeficiency virus (HIV) is the infectious agent causative of the acquired immune deficiency syndrome (AIDS). The number of HIV-infected people in the globe is incredibly large. Contrary to the big contamination rates, the incidence recently reported to AIDS-related deaths are fairly lower, less than 5 % of the total infected population. The reduced rates of the AIDS-associated deaths rely primarily on the growing availability, variety and efficiency of the antiretroviral treatments. During the initial molecular events of the HIV infectivity, the glycoprotein gp120 on the HIV envelop must interact with CD4 and heparan sulfate (HS) proteoglycans on the surface of the host cells in order to enable HIV attachment, fusion and entry into these cells...
January 27, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28133805/evolution-of-b-cell-analysis-and-env-trimer-redesign
#14
REVIEW
Gunilla B Karlsson Hedestam, Javier Guenaga, Martin Corcoran, Richard T Wyatt
HIV-1 and its surface envelope glycoproteins (Env), gp120 and gp41, have evolved immune evasion strategies that render the elicitation of effective antibody responses to the functional Env entry unit extremely difficult. HIV-1 establishes chronic infection and stimulates vigorous immune responses in the human host; forcing selection of viral variants that escape cellular and antibody (Ab)-mediated immune pressure, yet possess contemporary fitness. Successful survival of fit variants through the gauntlet of the human immune system make this virus and these glycoproteins a formidable challenge to target by vaccination, requiring a systematic approach to Env mimetic immunogen design and evaluation of elicited responses...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28128418/p2x7-receptor-in-the-hippocampus-is-involved-in-gp120-induced-cognitive-dysfunction
#15
Y Liu, G Q Chen, B Y Liu, Q Chen, Y M Qian, S S Qin, C L Liu, C S Xu
To investigate the role of the P2X7 receptor in learning and memory dysfunction induced by HIV-1 envelope glycoprotein gp120 (gp120), we established HIV-1-associated dementia (HAD) animal models by intracerebroventricular (ICV) infusion of gp120 in rats. We observed gp120-induced cognitive dysfunction in the radial arm water maze test. Results showed that rats in the gp120 groups had longer escape latencies and more errors compared to those in the control group. For example, the average trial time in the 50-ng/day-gp120 group on day eight (16...
January 23, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28125767/peptide-paratope-mimics-of-the-broadly-neutralizing-hiv-1-antibody-b12
#16
Christina Haußner, Dominik Damm, Anette Rohrhofer, Sandra Nirschl, Barbara Schmidt, Jutta Eichler
The broadly neutralizing HIV-1 antibody b12 recognizes the CD4 binding site of the HIV-1 envelope glycoprotein gp120, and efficiently neutralizes HIV-1 infections in vitro and in vivo. Based on the 3D structure of a b12 - gp120 complex, we have designed an assembled peptide (b12-M) that presents the parts of the three heavy chain complementarity determining regions (CDRs) of b12, which contain the contact sites of the antibody for gp120. This b12 mimetic peptide, as well as a truncated peptide presenting only two of the three heavy chain CDRs of b12, were shown to recognize gp120 in a b12-related fashion, as well as to inhibit HIV-1 infection, demonstrating a functional mimicry of b12 by the paratope mimetic peptides...
January 26, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28122982/lack-of-adcc-breadth-of-human-non-neutralizing-anti-hiv-1-antibodies
#17
Timothée Bruel, Florence Guivel-Benhassine, Valérie Lorin, Hugues Lortat-Jacob, Françoise Baleux, Katia Bourdic, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, Olivier Schwartz
: Anti-HIV-1 non-neutralizing antibodies (nnAbs) capable of antibody-dependent cellular cytotoxicity (ADCC) have been identified as a protective immune correlate in the RV144 vaccine efficacy trial. Broadly neutralizing antibodies (bNAbs) also mediate ADCC in cell culture and rely on their Fc region for optimal efficacy in animal models. Here, we selected 9 monoclonal nnAbs and 5 potent bNAbs, targeting various epitopes and conformations of the gp120/41 complex, and analyzed the potency of the two types of antibodies to bind and eliminate HIV-1-infected cells in culture...
January 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28122974/monoclonal-antibodies-to-v2-v3-the-cd4-binding-site-and-gp41-hiv-1-mediate-phagocytosis-in-a-dose-dependent-manner
#18
Thomas Musich, Liuzhe Li, Lily Liu, Susan Zolla-Pazner, Marjorie Robert-Guroff, Miroslaw K Gorny
: In light of weak or absent neutralizing activity mediated by anti-V2 monoclonal Abs (mAbs), we tested whether they can mediate Ab-dependent cellular phagocytosis (ADCP) which is an important element of anti-HIV-1 immunity. We tested six anti-V2 mAbs and compared them with 21 mAbs specific for V3, the CD4-binding site (CD4bs), and gp41 derived from HIV-1 chronically infected individuals and produced by hybridoma cells. ADCP activity was measured by flow cytometry using uptake by THP-1 monocytic cells of fluorescent beads coated with gp120, gp41, BG505 SOSIP...
January 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28116378/bifunctional-bispidine-derivatives-for-copper-64-labelling-and-positron-emission-tomography
#19
Amandine Roux, Raphaël Gillet, Sandrine Huclier-Markai, Laurence Ehret-Sabatier, Loïc J Charbonnière, Aline M Nonat
The first radiolabelling studies of a bispidine (3,7-diazabicyclo[3.3.1]nonane) derivative substituted by a glycinate pendant arm (L1) with (64)Cu are reported. Labelling was fast and easily performed at room temperature and in a wide range of pH values. Under these conditions, radiochemical yields over 90% were achieved within 5 minutes at micromolar concentration of the ligand. A bifunctional analogue of L1 (L2) has been obtained by introducing an l-lysine amino acid on the bispidine skeleton. Ligand L2 demonstrates good radiolabelling capacities at room temperature and in water (pH 4 to pH 6)...
January 24, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28107387/neuronal-cell-death-and-degeneration-through-increased-nitroxidative-stress-and-tau-phosphorylation-in-hiv-1-transgenic-rats
#20
Young-Eun Cho, Myoung-Hwa Lee, Byoung-Joon Song
The underlying mechanisms for increased neurodegeneration and neurocognitive deficits in HIV-infected people are unclear. Therefore, this study was aimed to investigate the mechanisms of increased neurodegeneration in 5-month old male HIV-1 Transgenic (Tg) rats compared to the age- and gender-matched wild-type (WT) by evaluating histological changes and biochemical parameters of the key proteins involved in the cell death signaling and apoptosis. Histological and immunohistochemical analyses revealed decreased neuronal cells with elevated astrogliosis in HIV-1 Tg rats compared to WT...
2017: PloS One
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