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https://www.readbyqxmd.com/read/28916807/envelope-glycoprotein-mobility-on-hiv-1-particles-depends-on-the-virus-maturation-state
#1
Jakub Chojnacki, Dominic Waithe, Pablo Carravilla, Nerea Huarte, Silvia Galiani, Jörg Enderlein, Christian Eggeling
Human immunodeficiency virus type 1 (HIV-1) assembles as immature particles, which require the proteolytic cleavage of structural polyprotein Gag and the clustering of envelope glycoprotein Env for infectivity. The details of mechanisms underlying Env clustering remain unknown. Here, we determine molecular dynamics of Env on the surface of individual HIV-1 particles using scanning fluorescence correlation spectroscopy on a super-resolution STED microscope. We find that Env undergoes a maturation-induced increase in mobility, highlighting diffusion as one cause for Env clustering...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916320/exosomes-carring-gag-env-of-alv-j-possess-negative-effect-on-immunocytes
#2
Guihua Wang, Zhenzhen Wang, Pingping Zhuang, Xiaomin Zhao, Ziqiang Cheng
J subgroup avian leukosis virus (ALV-J) is an exogenous retrovirus of avian. A key feature of ALV-J infection is leading to severe immunosuppressive characteristic of diseases. Viral components of retrovirus were reported closely associated with immunosuppression, and several similarities between exosomes and retrovirus preparations have lead to the hypotheses of retrovirus hijacker exosomes pathway. In this study, we purified exosomes from DF-1 cells infected and uninfected by ALV-J. Electron microscopy and mass spectrometry (MS) analysis showed that ALV-J not only increased the production of exosomes from ALV-J infected DF-1 cells (Exo-J) but also stimulated some proteins expression, especially ALV-J components secreted in exosomes...
September 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28916265/glycans-function-as-anchors-for-antibodies-and-help-drive-hiv-broadly-neutralizing-antibody-development
#3
Raiees Andrabi, Ching-Yao Su, Chi-Hui Liang, Sachin S Shivatare, Bryan Briney, James E Voss, Salar Khan Nawazi, Chung-Yi Wu, Chi-Huey Wong, Dennis R Burton
Apex broadly neutralizing HIV antibodies (bnAbs) recognize glycans and protein surface close to the 3-fold axis of the envelope (Env) trimer and are among the most potent and broad Abs described. The evolution of apex bnAbs from one donor (CAP256) has been studied in detail and many Abs at different stages of maturation have been described. Using diverse engineering tools, we investigated the involvement of glycan recognition in the development of the CAP256.VRC26 Ab lineage. We found that sialic acid-bearing glycans were recognized by germline-encoded and somatically mutated residues on the Ab heavy chain...
September 8, 2017: Immunity
https://www.readbyqxmd.com/read/28911033/formulation-of-chitosan-with-the-polyepitope-hiv-1-protein-candidate-vaccine-efficiently-boosts-cellular-immune-responses-in-mice
#4
Ehsan Ollah Jazaeri, Atiyeh Mahdavi, Asghar Abdoli
Human immunodeficiency virus-1 (HIV-1) continues to be a major global public health issue and priority. Despite the variety of antiretroviral therapies, it seems that an effective vaccine against HIV-1 is still very necessary. An ideal HIV-1 vaccine should be able to elicit both humoral and cellular immunities. In this respect, polyepitope vaccines, incorporated from several conserved regions of HIV-1 proteins, have received much attention recently. Herein, the immunogenicity of the HIV-1 polyepitope protein-based candidate vaccines was evaluated in BALB/c mice...
November 30, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28893277/development-of-an-hiv-vaccine-using-a-vesicular-stomatitis-virus-vector-expressing-designer-hiv-1-envelope-glycoproteins-to-enhance-humoral-responses
#5
REVIEW
Trina Racine, Gary P Kobinger, Eric J Arts
Vesicular stomatitis virus (VSV), like many other Rhabdoviruses, have become the focus of intense research over the past couple of decades based on their suitability as vaccine vectors, transient gene delivery systems, and as oncolytic viruses for cancer therapy. VSV as a vaccine vector platform has multiple advantages over more traditional viral vectors including low level, non-pathogenic replication in diverse cell types, ability to induce both humoral and cell-mediate immune responses, and the remarkable expression of foreign proteins cloned into multiple intergenic sites in the VSV genome...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28893272/killed-whole-hiv-vaccine-employing-a-well-established-strategy-for-antiviral-vaccines
#6
REVIEW
C Yong Kang, Yong Gao
The development of an efficient prophylactic HIV vaccine has been one of the major challenges in infectious disease research during the last three decades. Here, we present a mini review on strategies employed for the development of HIV vaccines with an emphasis on a well-established vaccine technology, the killed whole-virus vaccine approach. Recently, we reported an evaluation of the safety and the immunogenicity of a genetically modified and killed whole-HIV-1 vaccine designated as SAV001 [1]. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence of the Env signal peptide with that of honeybee melittin to produce an avirulent and replication efficient HIV-1...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28890362/microsecond-dynamics-and-network-analysis-of-the-hiv-1-sosip-env-trimer-reveal-collective-behavior-and-conserved-microdomains-of-the-glycan-shield
#7
Thomas Lemmin, Cinque Soto, Jonathan Stuckey, Peter D Kwong
The trimeric HIV-1-envelope (Env) spike is one of the most glycosylated protein complexes known, with roughly half its mass comprising host-derived N-linked glycan. Here we use molecular dynamics to provide insight into its structural dynamics and into how both protomer and glycan movements coordinate to shield the Env protein surface. A 2-μs molecular dynamics simulation of a fully glycosylated atomistic model of the HIV-1 SOSIP Env trimer revealed a spectrum of protomer-scissoring and trimer-opening movements...
August 24, 2017: Structure
https://www.readbyqxmd.com/read/28878130/an-ancestral-retroviral-protein-identified-as-a-therapeutic-target-in-type-1-diabetes
#8
Sandrine Levet, Julie Medina, Julie Joanou, Amandine Demolder, Nelly Queruel, Kevin Réant, Matthieu Normand, Marine Seffals, Julie Dimier, Raphaële Germi, Thomas Piofczyk, Jacques Portoukalian, Jean-Louis Touraine, Hervé Perron
Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W-Env) has been involved in multiple sclerosis pathogenesis. Investigations to detect HERV-W-Env in a few other autoimmune diseases were negative, except in type-1 diabetes (T1D). In patients suffering from T1D, HERV-W-Env protein was detected in 70% of sera, and its corresponding RNA was detected in 57% of peripheral blood mononuclear cells...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28878089/hla-b-14-02-restricted-env-specific-cd8-t-cell-activity-has-highly-potent-antiviral-efficacy-associated-with-immune-control-of-hiv-infection
#9
Ellen M Leitman, Christian B Willberg, Ming-Han Tsai, Huabiao Chen, Søren Buus, Fabian Chen, Lynn Riddell, David Haas, Jacques Fellay, James J Goedert, Alicja Piechocka-Trocha, Bruce D Walker, Jeffrey Martin, Steven Deeks, Steven M Wolinsky, Jeremy Martinson, Maureen Martin, Ying Qi, Asier Sáez-Cirión, Otto O Yang, Philippa C Matthews, Mary Carrington, Philip J R Goulder
Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8+ T-cell responses. We here focus on HLA-B*14, that protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env-specific (ERYLKDQQL, 'HLA-B*14-EL9'). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, 'HLA-B*14-DA9'). Using HLA-B*14/peptide-saporin conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28878072/high-throughput-protein-engineering-improves-the-antigenicity-and-stability-of-soluble-hiv-1-envelope-glycoprotein-sosip-trimers
#10
Jonathan T Sullivan, Chidananda Sulli, Alberto Nilo, Anila Yasmeen, Gabriel Ozorowski, Rogier W Sanders, Andrew B Ward, P J Klasse, John P Moore, Benjamin J Doranz
Soluble envelope glycoprotein (Env) trimers (SOSIP.664 gp140) are attractive HIV-1 vaccine candidates, with structures that mimic the native membrane-bound Env spike (gp160). Since engineering trimers can be limited by the difficulty of rationally predicting beneficial mutations, here we used a more comprehensive mutagenesis approach with the goal of identifying trimer variants with improved antigenic and stability properties. We created 341 cysteine pairs at predicted points of stabilization throughout gp140, 149 proline residue substitutions at every residue of the gp41 ectodomain, and 362 space-filling residue substitutions at every hydrophobic and aromatic residue in gp140...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28870557/retroviral-envelope-proteins-involvement-in-neuropathogenesis
#11
REVIEW
Dorte Tranberg Hansen, Thor Petersen, Tove Christensen
The primary disease caused by infection with the exogenous human retroviruses, human immunodeficiency virus 1 (HIV-1) or human T-cell lymphotropic virus 1 (HTLV-1), may overlay manifestations of additional autoimmune pathogenesis. Currently, a role for human endogenous retroviruses (HERVs) is also emerging in some autoimmune/immune-mediated diseases, particularly in multiple sclerosis (MS). Both exogenous and endogenous retroviruses have the potential to elicit the processes leading to autoimmune disease. The pathogenicity of the retroviral envelope protein (Env) is a key player with notable importance in neuroimmune diseases...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28870097/glycosylation-profiling-to-evaluate-glycoprotein-immunogens-against-hiv-1
#12
Anna-Janina Behrens, Weston B Struwe, Max Crispin
Introduction Much of the efforts to develop a vaccine against the human immunodeficiency virus (HIV) have focused on the design of recombinant mimics of the viral attachment glycoprotein (Env). The leading immunogens exhibit native-like antigenic properties and are being investigated for their ability to induce broadly neutralizing antibodies (bNAbs). Understanding the relative abundance of glycans at particular glycosylation sites on these immunogens is important as most bNAbs have evolved to recognize or evade the dense coat of glycans that masks much of the protein surface...
September 5, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28837840/development-of-a-recombinant-yellow-fever-vector-expressing-a-hiv-clade-c-founder-envelope-gp120
#13
Jae-Sung Yu, Hua-Xin Liao, Jamie Pritchett, Cindy Bowman, Callie Vivian, Robert Parks, Shi-Mao Xia, Melissa Cooper, Wilton B Williams, Mattia Bonsignori, Steven G Reed, Meng Chen, Nathan Vandergrift, Charles M Rice, Barton F Haynes
Development of a HIV-1 vaccine is a major global priority. The yellow fever virus (YFV) attenuated vaccine 17D is among the most effective of currently used vaccines. However, the stability of the YFV17D vector when carrying non-flavivirus genes has been problematic. We have constructed and expressed HIV-1 Env in YFV17D with either single transmembrane (STM) or double transmembrane (DTM) YFV E protein domains for the development of anti-HIV antibodies. Here we describe modifications of the YFV17D vector such that HIV-1 Env gp120 is expressed in up to 5 passages in Vero cells...
August 31, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28827559/selection-of-nanobodies-with-broad-neutralizing-potential-against-primary-hiv-1-strains-using-soluble-subtype-c-gp140-envelope-trimers
#14
Kathrin Koch, Sarah Kalusche, Jonathan L Torres, Robyn L Stanfield, Welbeck Danquah, Kamal Khazanehdari, Hagen von Briesen, Eric R Geertsma, Ian A Wilson, Ulrich Wernery, Friedrich Koch-Nolte, Andrew B Ward, Ursula Dietrich
Broadly neutralizing antibodies (bnAbs) against HIV-1 protect from infection and reduce viral load upon therapeutic applications. However no vaccine was able so far to induce bnAbs demanding their expensive biotechnological production. For clinical applications, nanobodies (VHH) derived from heavy chain only antibodies from Camelidae, may be better suited due to their small size, high solubility/stability and extensive homology to human VH3 genes. Here we selected broadly neutralizing nanobodies by phage display after immunization of dromedaries with different soluble trimeric envelope proteins derived from HIV-1 subtype C...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28816583/mammalian-cell-surface-display-for-monoclonal-antibody-based-facs-selection-of-viral-envelope-proteins
#15
Tim-Henrik Bruun, Veronika Grassmann, Benjamin Zimmer, Benedikt Asbach, David Peterhoff, Alexander Kliche, Ralf Wagner
The elicitation of broadly and efficiently neutralizing antibodies in humans by active immunization is still a major obstacle in the development of vaccines against pathogens such as the human immunodeficiency virus (HIV), influenza virus, hepatitis C virus or cytomegalovirus. Here, we describe a mammalian cell surface display and monoclonal antibody (mAb)-mediated panning technology that allows affinity-based selection of envelope (Env) variants from libraries. To this end, we established an experimental setup featuring: 1) single and site specific integration of Env to link genotype and phenotype, 2) inducible Env expression to avoid cytotoxicity effects, 3) translational coupling of Env and enhanced green fluorescent protein expression to normalize for Env protein levels, and 4) display on HEK cells to ensure native folding and mammalian glycosylation...
August 17, 2017: MAbs
https://www.readbyqxmd.com/read/28814388/the-impact-of-poxvirus-vector-priming-protein-co-administration-and-vaccine-intervals-on-hiv-gp120-vaccine-elicited-antibody-magnitude-and-function-in-infant-macaques
#16
Bonnie Phillips, Genevieve G Fouda, Josh Eudailey, Justin Pollara, Alan D Curtis, Erika Kunz, Maria Dennis, Xiaoying Shen, Camden Bay, Michael Hudgens, David Pickup, S Munir Alam, Amir Ardeshir, Pamela A Kozlowski, Koen K A Van Rompay, Guido Ferrari, M Anthony Moody, Sallie Permar, Kristina De Paris
Despite success in reducing vertical HIV transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (MTCT) of HIV in infants. Thus, a pediatric vaccine is needed to eradicate oral HIV infections in newborns and infants. Utilizing the infant rhesus macaque model, we compared 3 different vaccine regimens: (i) HIV Env protein only; (ii) a poxvirus vector (MVA)-HIV Env prime/HIV Env protein boost, and (iii) co-administration of HIV Env protein and MVA-HIV Env at all time points...
August 16, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28794041/interferon-inducible-cd169-siglec1-attenuates-anti-hiv-1-effects-of-ifn-%C3%AE
#17
Hisashi Akiyama, Nora-Guadalupe Pina Ramirez, Gregory Gibson, Christopher Kline, Simon Watkins, Zandrea Ambrose, Suryaram Gummuluru
A hallmark of HIV-1 infection in vivo is chronic immune activation concomitant with type I interferon (IFN) production. Although type I IFN induces an antiviral state in many cell types, HIV-1 can replicate in vivo via mechanisms that have remained unclear. We have recently identified a type I IFN-inducible protein CD169 as the HIV-1 attachment factor on dendritic cells (DCs) that can mediate robust infection of CD4(+) T cells in trans. Since CD169 expression on macrophages is also induced by type I IFN, we hypothesized that type I IFN-inducible CD169 could facilitate productive HIV-1 infection in myeloid cells in cis and CD4(+) T cells in trans and thus offset antiviral effects of type I IFN...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28763028/rous-sarcoma-virus-rna-stability-element-inhibits-deadenylation-of-mrnas-with-long-3-utrs
#18
Vidya Balagopal, Karen L Beemon
All retroviruses use their full-length primary transcript as the major mRNA for Group-specific antigen (Gag) capsid proteins. This results in a long 3' untranslated region (UTR) downstream of the termination codon. In the case of Rous sarcoma virus (RSV), there is a 7 kb 3'UTR downstream of the gag terminator, containing the pol, env, and src genes. mRNAs containing long 3'UTRs, like those with premature termination codons, are frequently recognized by the cellular nonsense-mediated mRNA decay (NMD) machinery and targeted for degradation...
August 1, 2017: Viruses
https://www.readbyqxmd.com/read/28758637/dna-prime-protein-boost-vaccination-elicits-robust-humoral-response-in-rhesus-macaques-using-oligomeric-simian-immunodeficiency-virus-envelope-and-advax-delta-inulin-adjuvant
#19
Veena Menon, Victor I Ayala, Sneha P Rangaswamy, Irene Kalisz, Stephen Whitney, Lindsey Galmin, Asma Ashraf, Celia LaBranche, David Montefiori, Nikolai Petrovsky, Vaniambadi S Kalyanaraman, Ranajit Pal
The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. To test this hypothesis, two SIV envelope proteins were formulated with delta inulin-based adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140-gp145 from SIVmac251 and SIVsmE660 was purified to homogeneity...
August 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28743743/characterization-of-a-stable-hiv-1-b-c-recombinant-soluble-and-trimeric-envelope-glycoprotein-env-highly-resistant-to-cd4-induced-conformational-changes
#20
Rajesh Kumar, Gabriel Ozorowski, Vivek Kumar, Lauren G Holden, Tripti Shrivastava, Shilpa Patil, Suprit Deshpande, Andrew B Ward, Jayanta Bhattacharya
The HIV-1 envelope (Env) is a glycoprotein which is a trimer of heterodimer containing gp120 and gp41 subunits, mediates virus entry and is a major target of broadly neutralizing antibodies (bnAbs) developed during infection in some individuals. The engagement of the HIV-1 gp120 glycoprotein to the host CD4 protein triggers conformational changes in gp120 that allows its binding to coreceptors, and is necessary for virus entry to establish infection. Native-like HIV-1 Env immunogens representing distinct clades have been proposed to improve immunogenicity of bnAbs...
July 25, 2017: Journal of Biological Chemistry
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