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https://www.readbyqxmd.com/read/28550120/hiv-1-decreases-nrf2-are-activity-and-phagocytic-function-in-alveolar-macrophages
#1
Bashar S Staitieh, Lingmei Ding, Wendy A Neveu, Paul Spearman, David M Guidot, Xian Fan
Respiratory complications occur frequently in individuals living with human immunodeficiency-1 virus (HIV) infection, and there is evidence that HIV-related oxidative stress impairs alveolar macrophage immune function. We hypothesized that nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master transcription factor that activates the antioxidant response element (ARE) and regulates antioxidant defenses, has an important role in alveolar macrophage (AMs) immune dysfunction in individuals with HIV infections...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28539451/reducing-v3-antigenicity-and-immunogenicity-on-soluble-native-like-hiv-1-env-sosip-trimers
#2
Rajesh P Ringe, Gabriel Ozorowski, Kimmo Rantalainen, Weston B Struwe, Katie Matthews, Jonathan L Torres, Anila Yasmeen, Christopher A Cottrell, Thomas J Ketas, Celia C LaBranche, David C Montefiori, Albert Cupo, Max Crispin, Ian A Wilson, Andrew B Ward, Rogier W Sanders, P J Klasse, John P Moore
Native-like trimers of the SOSIP design are being developed as immunogens in human immunodeficiency virus type 1 (HIV-1) vaccine development programs. These trimers display the epitopes for multiple broadly neutralizing antibodies (bNAbs), but can also expose binding sites for some types of non-neutralizing antibodies (non-NAbs). Among the latter are epitopes in the gp120 V3 region that are highly immunogenic when SOSIP trimers are evaluated in animal models. It is presently uncertain whether antibodies against V3 can interfere with the induction of NAbs, but there are good arguments in favor of suppressing such "off-target" immune responses...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539449/anti-hiv-1-adcc-antibodies-following-latency-reversal-and-treatment-interruption
#3
Wen Shi Lee, Anne B Kristensen, Thomas A Rasmussen, Martin Tolstrup, Lars Østergaard, Ole S Søgaard, Bruce D Wines, P Mark Hogarth, Arnold Reynaldi, Miles P Davenport, Sean Emery, Janaki Amin, David A Cooper, Virginia L Kan, Julie Fox, Henning Gruell, Matthew S Parsons, Stephen J Kent
There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRA) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539445/structure-of-simian-immunodeficiency-virus-envelope-spikes-bound-with-cd4-and-monoclonal-antibody-36d5
#4
Guiqing Hu, Jun Liu, Kenneth H Roux, Kenneth A Taylor
The HIV-1/SIV envelope spike (Env) mediates the viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the co-receptor binding site and is a target for neutralizing antibodies. We have used cryoelectron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody 36D5 to gp120 of the SIV Env. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest the antibody exerts its neutralization effect by blocking the co-receptor binding site...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28533249/the-myxobacterial-metabolite-soraphen-a-inhibits-hiv-1-by-reducing-virus-production-and-altering-virion-composition
#5
Eric Fleta-Soriano, Katarína Smutná, Javier P Martinez, Cristina Lorca Oró, S Kashif Sadiq, Gilles Mirambeau, Carmen Lopez-Iglesias, Marta Bosch, Albert Pol, Mark Brönstrup, Juana Diez, Andreas Meyerhans
Soraphen A is a myxobacterial metabolite that blocks the acetyl-CoA carboxylase of the host, and was previously identified as a novel HIV inhibitor. Here we report that Soraphen A acts by reducing virus production and altering the gp120 virion content, impacting entry capacity and infectivity. These effects are partially reversed by addition of palmitic acid, suggesting inhibition of HIV Env palmitoylation as one of the mechanisms of antiviral action.
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28521215/adaptation-of-hiv-1-to-cells-with-low-expression-of-the-ccr5-coreceptor
#6
Nicole Espy, Beatriz Pacheco, Joseph Sodroski
The binding of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer ((gp120/gp41)3) to the receptors CD4 and CCR5 triggers virus entry into host cells. To identify Env regions that respond to CCR5 binding, HIV-1 was serially passaged on a CD4-positive canine cell line expressing progressively lower levels of CCR5. HIV-1 replication was observed in cells expressing ~1300 CCR5 molecules/cell. Env changes that conferred this low-CCR5 replication phenotype were located outside of the known CCR5-binding region of the gp120 Env subunit and did not apparently increase CCR5 binding affinity...
May 15, 2017: Virology
https://www.readbyqxmd.com/read/28517931/correction-to-synthesis-antiviral-potency-in-vitro-admet-and-x-ray-structure-of-potent-cd4-mimics-as-entry-inhibitors-that-target-the-phe43-cavity-of-hiv-1-gp120
#7
Francesca Curreli, Young Do Kwon, Dmitry S Belov, Ranjith R Ramesh, Alexander V Kurkin, Andrea Altieri, Peter D Kwong, Asim K Debnath
No abstract text is available yet for this article.
May 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28514686/glycine-substitution-at-helix-to-coil-transitions-facilitates-the-structural-determination-of-a-stabilized-subtype-c-hiv-envelope-glycoprotein
#8
Javier Guenaga, Fernando Garces, Natalia de Val, Robyn L Stanfield, Viktoriya Dubrovskaya, Brett Higgins, Barbara Carrette, Andrew B Ward, Ian A Wilson, Richard T Wyatt
Advances in HIV-1 envelope glycoprotein (Env) design generate native-like trimers and high-resolution clade A, B, and G structures and elicit neutralizing antibodies. However, a high-resolution clade C structure is critical, as this subtype accounts for the majority of HIV infections worldwide, but well-ordered clade C Env trimers are more challenging to produce due to their instability. Based on targeted glycine substitutions in the Env fusion machinery, we defined a general approach that disfavors helical transitions leading to post-fusion conformations, thereby favoring the pre-fusion state...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28494151/design-of-hiv-co-receptor-derived-peptides-that-inhibit-viral-entry-at-submicromolar-concentrations
#9
Kostyantyn D Bobyk, Sivakoteswara R Mandadapu, Katheryn Lohith, Christina Guzzo, Abhishek Bhargava, Paolo Lusso, Carole A Bewley
HIV/AIDS continues to pose an enormous burden on global health. Current HIV therapeutics include inhibitors that target the enzymes HIV protease, reverse transcriptase and integrase, along with viral entry inhibitors that block the initial steps of HIV infection by preventing membrane fusion or virus-coreceptor interactions. With regard to the latter, peptides derived from the HIV coreceptor CCR5 were previously shown to modestly inhibit entry of CCR5-tropic HIV strains, with a peptide containing residues 178-191 of the second extracellular loop (peptide 2C) showing the strongest inhibition...
May 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28493891/antibody-to-hsv-gd-peptide-induced-by-vaccination-does-not-protect-against-hsv-2-infection-in-hsv-2-seronegative-women
#10
Peter B Gilbert, Jean-Louis Excler, Georgia D Tomaras, Lindsay N Carpp, Barton F Haynes, Hua-Xin Liao, David C Montefiori, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Jaranit Kaewkungwal, Gustavo H Kijak, Sodsai Tovanabutra, Donald P Francis, Carter Lee, Faruk Sinangil, Phillip W Berman, Nakorn Premsri, Prayura Kunasol, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Rhoda Morrow, Lawrence Corey, Jerome H Kim
BACKGROUND: In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX® B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence...
2017: PloS One
https://www.readbyqxmd.com/read/28490736/extracellular-vesicles-carry-hiv-env-and-facilitate-hiv-infection-of-human-lymphoid-tissue
#11
Anush Arakelyan, Wendy Fitzgerald, Sonia Zicari, Christophe Vanpouille, Leonid Margolis
Cells productively infected with HIV-1 release virions along with extracellular vesicles (EVs) whose biogenesis, size, and physical properties resemble those of retroviruses. Here, we found that a significant number of EVs (exosomes) released by HIV-1 infected cells carry gp120 (Env), a viral protein that mediates virus attachment and fusion to target cells, and also facilitates HIV infection in various indirect ways. Depletion of viral preparations of EVs, in particular of those that carry gp120, decreases viral infection of human lymphoid tissue ex vivo...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490585/crosslinking-of-a-cd4-mimetic-miniprotein-with-hiv-1-env-gp140-alters-kinetics-and-specificities-of-antibody-responses-against-hiv-1-env-in-macaques
#12
Xiaoying Shen, Willy M Bogers, Nicole L Yates, Guido Ferrari, Antu K Dey, William T Williams, Frederick H Jaeger, Kevin Wiehe, Sheetal Sawant, S Munir Alam, Celia C LaBranche, David C Montefiori, Loic Martin, Indresh Srivastava, Jonathan Heeney, Susan W Barnett, Georgia D Tomaras
Evaluation of the epitope specificities, location (systemic, mucosal) and effector function of antibodies elicited by novel HIV-1 immunogens engineered to improve exposure of specific epitopes is critical for HIV-1 vaccine development. Utilizing an array of humoral assays, we evaluated the magnitude, epitope specificity, avidity and function of systemic and mucosal immune responses elicited by a vaccine regimen containing Env cross-linked to a CD4 mimetic miniprotein (gp140-M64U1) in rhesus macaques. Crosslinking of gp140 Env with M64U1 resulted in an earlier increase in both the magnitude and avidity of the IgG binding response compared to Env protein alone...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28484468/the-membrane-proximal-region-of-c-c-chemokine-receptor-type-5-participates-in-the-infection-of-hiv-1
#13
Yue Tan, Pei Tong, Junyi Wang, Lei Zhao, Jing Li, Yang Yu, Ying-Hua Chen, Ji Wang
The initial infection and transmission of HIV-1 requires C-C chemokine receptor type 5 (CCR5). Here, we report that the membrane-proximal region (MPR, aa 22-38) of CCR5 participates in the infection of HIV-1. First, MPR-specific antibodies elicited in mice dose-dependently inhibited the infection of CCR5-tropic HIV-1. Second, substituting MPR with the same region from other co-receptors significantly impaired HIV-1 infection, while the key residues identified by alanine scanning mutagenesis formed an exposed leucine zipper-like structure...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28484447/hiv-1-and-siv-predominantly-use-ccr5-expressed-on-a-precursor-population-to-establish-infection-in-t-follicular-helper-cells
#14
Yin Xu, Chansavath Phetsouphanh, Kazuo Suzuki, Anu Aggrawal, Stephanie Graff-Dubois, Michael Roche, Michelle Bailey, Sheilajen Alcantara, Kieran Cashin, Rahuram Sivasubramaniam, Kersten K Koelsch, Brigitte Autran, Richard Harvey, Paul R Gorry, Arnaud Moris, David A Cooper, Stuart Turville, Stephen J Kent, Anthony D Kelleher, John Zaunders
BACKGROUND: T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4(+) T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28483193/expression-of-complete-siv-p27-gag-and-hiv-gp120-engineered-outer-domains-targeted-by-broadly-neutralizing-antibodies-in-live-rubella-vectors
#15
Konstantin Virnik, Edmund Nesti, Cody Dail, Max Hockenbury, Yisheng Ni, Barbara K Felber, William R Schief, Ira Berkower
Infection with HIV or SIV often elicits a potent immune response to viral antigens. This includes T cells and antibodies specific for Gag and Env antigens. In contrast, when given as a vaccine, the same antigens have been weak immunogens, unable to elicit antibodies with comparable titer, durability, or neutralizing activity. We have used the live attenuated rubella vaccine strain RA27/3 as a viral vector to express HIV and SIV antigens. By mimicking an HIV infection, these vectors could elicit stronger and more durable immunity to HIV antigens...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28472687/purification-characterization-and-biological-significance-of-mannose-binding-lectin-from-dioscorea-bulbifera-bulbils
#16
Mamta Sharma, Vishwanathreddy Hotpet, Sindhura B R, Kamalanathan A S, Bale M Swamy, Shashikala R Inamdar
Dioscorea bulbifera or air potato has been used as a folk remedy to treat cancer. A mannose binding lectin from bulbils of D. bulbifera was purified in a single step by affinity chromatography on mucin coupled Sepharose 4B column, determined by its fine sugar specificity by glycan array analysis and studied for its clinical potential in cancer and HIV research. SDS-PAGE showed that lectin is a monomer of Mr 24kDa. DBL agglutinated only rabbit erythrocytes and was inhibited by mucin, asialomucin, fetuin, asialofetuin and transferrin but not by any monosaccharides...
May 1, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28472629/an-in-vitro-model-to-mimic-selection-of-replication-competent-hiv-1-intersubtype-recombination-in-dual-or-superinfected-patients
#17
Bernard S Bagaya, Meijuan Tian, Gabrielle C Nickel, José F Vega, Yuejin Li, Ping He, Katja Klein, Jamie F S Mann, Wei Jiang, Eric J Arts, Yong Gao
The low frequency of HIV-1 recombinants within entire viral populations in both individual patients and in culture-based infection models impedes investigation of the underlying factors contributing either to the occurrence of recombinants or the survival of recombinants once they are formed. So far, most of the related studies have no consideration of recombinants' functionality. Here we established a Functional Recombinant Production (FRP) system to produce pure and functional HIV-1 intersubtype Env recombinants, and utilized 454 pyrosequencing to investigate the distribution of over 4,000 functional and non-functional recombination breakpoints from either the FRP system or dual infection cultures...
May 1, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28468877/preservation-of-peripheral-t-follicular-helper-cell-function-in-hiv-controllers
#18
Supranee Buranapraditkun, Franco Pissani, Jeffrey E Teigler, Bruce T Schultz, Galit Alter, Mary Marovich, Merlin L Robb, Michael A Eller, Jeff Martin, Steven Deeks, Nelson L Michael, Hendrik Streeck
The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28461065/tryptophan-375-stabilizes-the-outer-domain-core-of-gp120-for-hiv-vaccine-immunogen-design
#19
Duoyi Hu, Dane Bowder, Wenzhong Wei, Jesse Thompson, Mark A Wilson, Shi-Hua Xiang
The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W)...
April 28, 2017: Vaccine
https://www.readbyqxmd.com/read/28458036/a-heterologous-prime-boosting-strategy-with-replicating-vaccinia-virus-vectors-and-plant-produced-hiv-1-gag-dgp41-virus-like-particles
#20
Lydia R Meador, Sarah A Kessans, Jacquelyn Kilbourne, Karen V Kibler, Giuseppe Pantaleo, Mariano Esteban Roderiguez, Joseph N Blattman, Bertram L Jacobs, Tsafrir S Mor
Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation...
April 27, 2017: Virology
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