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https://www.readbyqxmd.com/read/28069361/dna-mva-protein-vaccination-of-rhesus-macaques-induces-hiv-specific-immunity-in-mucosal-associated-lymph-nodes-and-functional-antibodies
#1
Gerald K Chege, Wendy A Burgers, Tracey L Müller, Clive M Gray, Enid G Shephard, Susan W Barnett, Guido Ferrari, David Montefiori, Carolyn Williamson, Anna-Lise Williamson
Successful future HIV vaccines are expected to generate an effective cellular and humoral response against the virus in both the peripheral blood and mucosal compartments. We previously reported the development of DNA-C and MVA-C vaccines based on HIV-1 subtype C and demonstrated their immunogenicity when given in a DNA prime-MVA boost combination in a nonhuman primate model. In the current study, rhesus macaques previously vaccinated with a DNA-C and MVA-C vaccine regimen were re-vaccinated 3.5years later with MVA-C followed by a protein vaccine based on HIV-1 subtype C envelope formulated with MF59 adjuvant (gp140Env/MF59), and finally a concurrent boost with both vaccines...
January 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28057386/nanoparticles-decorated-with-viral-antigens-are-more-immunogenic-at-low-surface-density
#2
Matthew G Brewer, Anthony DiPiazza, Joshua Acklin, Changyong Feng, Andrea J Sant, Stephen Dewhurst
There is an urgent need to develop protective vaccines for high priority viral pathogens. One approach known to enhance immune responses to viral proteins is to display them on a nanoparticle (NP) scaffold. However, little is known about the effect of protein density on the B cell response to antigens displayed on NPs. To address this question HIV-1 Envelope (Env) and influenza hemagglutinin (HA) were displayed on a polystyrene-based NP scaffold at various densities - corresponding to mean antigen distances that span the range encountered on naturally occurring virions...
January 3, 2017: Vaccine
https://www.readbyqxmd.com/read/28056499/recognition-of-hiv-inactivating-peptide-triazoles-by-the-recombinant-soluble-env-trimer-bg505-sosip-664
#3
Kriti Acharya, Adel A Rashad, Francesca Moraca, Per Johan Klasse, John P Moore, Cameron Abrams, Irwin Chaiken
Peptide triazole (PT) antagonists interact with gp120 subunits of HIV-1 Env trimers to block host cell receptor interactions, trigger gp120 shedding, irreversibly inactivate virus and inhibit infection. Despite these enticing functions, understanding the structural mechanism of PT-Env trimer encounter has been limited. In this work, we combined competition interaction analysis and computational simulation to demonstrate PT binding to the recombinant soluble trimer, BG505 SOSIP.664, a stable variant that resembles native virus spikes in binding to CD4 receptor as well as known conformationally-dependent Env antibodies...
January 5, 2017: Proteins
https://www.readbyqxmd.com/read/28006952/comparison-of-antibody-responses-induced-by-rv144-vax003-and-vax004-vaccination-regimens
#4
Chitraporn Karnasuta, Siriwat Akapirat, Sirinan Madnote, Hathairat Savadsuk, Jiraporn Puangkaew, Surawach Rittiroongrad, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Punnee Pitisuttithum, Jaranit Kaewkungwal, Jim Tartaglia, Faruk Sinangil, Donald P Francis, Merlin Robb, Mark de Souza, Nelson L Michael, Jean-Louis Excler, Jerome H Kim, Robert J O'Connell, Nicos Karasavvas
The RV144 prime-boost regimen demonstrated efficacy against HIV acquisition while VAX003 and VAX004 did not. Although these trials differed by risk groups, immunization regimens and immunogens, antibody responses may have contributed to the differences observed in vaccine efficacy. We assessed HIV-specific IgG, both total and subclass, and IgA binding to HIV envelope (Env): gp120 proteins and CycV2 and CycV3 peptides and gp70V1V2 scaffolds in these 3 HIV vaccine trials. After two protein immunizations, IgG responses to 92TH023 gp120 (contained in ALVAC-HIV vaccine) were significantly higher in RV144 but responses to other Env were higher in the VAX trials lacking ALVAC-HIV...
December 22, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27998269/increased-t-cell-breadth-and-antibody-response-elicited-in-prime-boost-regimen-by-viral-vector-encoded-homologous-siv-gag-env-in-outbred-cd1-mice
#5
Anne-Marie Carola Andersson, Peter Johannes Holst
BACKGROUND: A major obstacle for the development of HIV vaccines is the virus' worldwide sequence diversity. Nevertheless, the presence of T cell epitopes within conserved regions of the virus' structural Gag protein and conserved structures in the envelope (env) sequence raises the possibility that cross-reactive responses may be induced by vaccination. In this study, the aim was to investigate the importance of antigenic match on immunodominance and breadth of obtainable T cell responses...
December 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27990140/insight-into-the-ervk-integrase-propensity-for-dna-damage
#6
Samantha Bray, Matthew Turnbull, Sherry Hebert, Renée N Douville
Retroviruses create permanently integrated proviruses that exist in the host genome. Retroviral genomes encode for functionally conserved gag, pro, pol, and env regions, as well as integrase (IN), which is required for retroviral integration. IN mediates viral genome insertion through 3' end processing of the viral DNA and the strand transfer reaction. This process requires the formation of a pre-integration complex, comprised of IN, viral DNA, and cellular proteins. Viral insertion causes DNA damage, leading to the requirement of host DNA repair mechanisms...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27959955/experimental-estimation-of-the-effects-of-all-amino-acid-mutations-to-hiv-s-envelope-protein-on-viral-replication-in-cell-culture
#7
Hugh K Haddox, Adam S Dingens, Jesse D Bloom
HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV's most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV's replication in cell culture...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27938679/single-n-glycosylation-site-of-bovine-leukemia-virus-su-is-involved-in-conformation-and-viral-escape
#8
Giorgia Rizzo, Katia Forti, Anna Serroni, Monica Cagiola, Sara Baglivo, Eleonora Scoccia, Antonio De Giuseppe
The bovine leukaemia virus (BLV) envelope protein (Env) is synthesized as a polyprotein precursor (gp72) proteolytically cleaved into the mature surface (SU) and transmembrane (TM) glycoproteins. The amino-terminal region of SU contains conformational epitopes F, G and H, which require a glycosylated SU to be recognized by monoclonal antibodies (MAbs) and antibodies from BLV-infected cattle. The SU contains eight asparagine (N) residues that are putative N-glycosylation sites. The N129, N203, N230 and N251 appear involved in carbohydrate binding, play an essential role in the in vitro infection...
December 25, 2016: Veterinary Microbiology
https://www.readbyqxmd.com/read/27928916/mouse-tetherin-enhances-moloney-murine-leukemia-virus-induced-syncytium-formation
#9
H S Kim, S Y Han, Y T Jung
Tetherin (also referred to as BST-2 or CD317) is an antiviral cellular restriction factor that inhibits the release of many enveloped viruses. It is a 30-36 kDa type II transmembrane protein, expression of which is induced by type I interferon. Mouse tetherin inhibits nascent cell-free particle release. However, it is unclear whether mouse tetherin restricts cell-to-cell spread of moloney murine leukemia virus (Mo-MLV) or whether is the mouse tetherin involved in syncytium formation. To examine cell-to-cell spread and syncytium formation of Mo-MLV in the presence or absence of mouse tetherin, R peptide (the cytoplasmic tail of the transmembrane protein (TM); 16 amino acids) truncated Env expressing vector was constructed...
2016: Acta Virologica
https://www.readbyqxmd.com/read/27928057/modulation-of-the-splicing-regulatory-function-of-srsf10-by-a-novel-compound-that-impairs-hiv-1-replication
#10
Lulzim Shkreta, Marco Blanchette, Johanne Toutant, Emmanuelle Wilhelm, Brendan Bell, Benjamin A Story, Ahalya Balachandran, Alan Cochrane, Peter K Cheung, P Richard Harrigan, David S Grierson, Benoit Chabot
We recently identified the 4-pyridinone-benzisothiazole carboxamide compound 1C8 as displaying strong anti-HIV-1 potency against a variety of clinical strains in vitro Here we show that 1C8 decreases the expression of HIV-1 and alters splicing events involved in the production of HIV-1 mRNAs. Although 1C8 was designed to be a structural mimic of the fused tetracyclic indole compound IDC16 that targets SRSF1, it did not affect the splice site shifting activity of SRSF1. Instead, 1C8 altered splicing regulation mediated by SRSF10...
December 7, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27928004/the-effect-of-hiv-1-env-on-serinc5-antagonism
#11
Saina Beitari, Shilei Ding, Qinghua Pan, Andrés Finzi, Chen Liang
: SERINC5 is able to restrict HIV-1 infection by drastically impairing the infectivity of viral particles. Current studies have shown that HIV-1 Nef protein counters SERINC5 through down regulating SERINC5 from the cell surface and preventing virion incorporation of SERINC5. In addition, the Env proteins of some HIV-1 strains can also overcome SERINC5 inhibition. However, it is unclear how HIV-1 Env does so and why HIV-1 has two mechanisms to resist SERINC5 inhibition. Results of this study show that neither Env nor Nef prevents high-level ectopic SERINC5 from incorporation into HIV-1 particles, except that Env, but not Nef, is able to resist the inhibition of virion-associated SERINC5...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27928002/adjuvanting-an-siv-vaccine-with-tlr-ligands-encapsulated-in-nanoparticles-induces-persistent-antibody-responses-and-enhanced-protection-in-trim5%C3%AE-restrictive-macaques
#12
Sudhir Pai Kasturi, Pamela A Kozlowski, Helder I Nakaya, Matheus C Burger, Pedro Russo, Mathew Pham, Yevgeniy Kovalenkov, Eduardo L V Silveira, Colin Havenar-Daughton, Samantha L Burton, Katie M Kilgore, Mathew J Johnson, Rafiq Nabi, Traci Legere, Zarpheen Jinnah Sher, Xuemin Chen, Rama R Amara, Eric Hunter, Steven E Bosinger, Paul Spearman, Shane Crotty, Francois Villinger, Cynthia A Derdeyn, Jens Wrammert, Bali Pulendran
: Our previous work has shown that antigens adjuvanted with specific ligands for toll-like receptor 4 (TLR4) and TLR7/8 encapsulated in poly (lactic-co-glycolic acid) (PLGA) based nanoparticles (NP), induced robust and durable immune responses in mice and macaques. We investigated the efficacy of these NP adjuvants in inducing protective immunity against simian immunodeficiency virus (SIV). Rhesus macaques (RMs) were immunized with NP containing TLR4 and TLR7/8 agonists mixed with soluble recombinant SIVmac239 derived envelope (Env) gp140 and Gag p55 (Protein), or with virus like particles (VLP) containing SIVmac239 Env and Gag...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27921323/the-application-of-strand-invasion-phenomenon-directed-by-peptide-nucleic-acid-pna-and-single-stranded-dna-binding-protein-ssb-for-the-recognition-of-specific-sequences-of-human-endogenous-retroviral-herv-w-family
#13
Grzegorz Machnik, Łukasz Bułdak, Jarosław Ruczyński, Tomasz Gąsior, Małgorzata Huzarska, Dariusz Belowski, Magdalena Alenowicz, Piotr Mucha, Piotr Rekowski, Bogusław Okopień
The HERV-W family of human endogenous retroviruses represents a group of numerous sequences that show close similarity in genetic composition. It has been documented that some members of HERV-W-derived expression products are supposed to play significant role in humans' pathology, such as multiple sclerosis or schizophrenia. Other members of the family are necessary to orchestrate physiological processes (eg, ERVWE1 coding syncytin-1 that is engaged in syncytiotrophoblast formation). Therefore, an assay that would allow the recognition of particular form of HERV-W members is highly desirable...
December 6, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27906032/infection-of-rhesus-macaques-with-a-pool-of-simian-immunodeficiency-virus-with-the-envelope-genes-from-acute-hiv-1-infections
#14
Kendall C Krebs, Meijuan Tian, Mohammed Asmal, Binhua Ling, Kenneth Nelson, Kenneth Henry, Richard Gibson, Yuejin Li, Weining Han, Robin J Shattock, Ronald S Veazey, Norman Letvin, Eric J Arts, Yong Gao
BACKGROUND: New simian-human immunodeficiency chimeric viruses with an HIV-1 env (SHIVenv) are critical for studies on HIV pathogenesis, vaccine development, and microbicide testing. Macaques are typically exposed to single CCR5-using SHIVenv which in most instances does not reflect the conditions during acute/early HIV infection (AHI) in humans. Instead of individual and serial testing new SHIV constructs, a pool of SHIVenv_B derived from 16 acute HIV-1 infections were constructed using a novel yeast-based SHIV cloning approach and then used to infect macaques...
November 25, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27902399/truncation-of-the-enzootic-nasal-tumor-virus-envelope-protein-cytoplasmic-tail-increases-env-mediated-fusion-and-infectivity
#15
Scott R Walsh, Jondavid G de Jong, Jacob P van Vloten, María Carla Rosales Gerpe, Lisa A Santry, Sarah K Wootton
Enzootic nasal tumor virus (ENTV) and Jaagsiekte sheep retrovirus (JSRV) are highly related ovine betaretroviruses that induce nasal and lung tumors in small ruminants, respectively. While the ENTV and JSRV envelope (Env) glycoproteins mediate virus entry using the same cellular receptor, the GPI-linked protein hyaluronoglucosaminidase, ENTV Env pseudovirions mediate entry into cells from a much more restricted range of species than do JSRV Env pseudovirions. Unlike JSRV Env, ENTV Env does not induce cell fusion at pH 5...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27899035/delayed-seroconversion-to-htlv-ii-is-associated-with-a-stop-codon-mutation-in-the-pol-gene
#16
Syamalima Dube, Dipak K Dube, Lynn Abbott, Jordan Glaser, Bernard J Poiesz
A known HIV-1-positive intravenous drug user was found to be human T cell lymphoma/leukemia virus-II (HTLV-II) DNA positive by polymerase chain reaction but seronegative in a screening ELISA. He was consistently DNA positive but took 2 years to fully seroconvert. Sequencing of the HTLV-II strain in his cultured T lymphocytes indicated that it is a prototypical type A strain with no major differences in the long terminal repeat DNA sequence, nor major amino acid differences in the Gag, Env, Tax, and Rex proteins...
January 3, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27894306/first-phase-i-human-clinical-trial-of-a-killed-whole-hiv-1-vaccine-demonstration-of-its-safety-and-enhancement-of-anti-hiv-antibody-responses
#17
Eunsil Choi, Chad J Michalski, Seung Ho Choo, Gyoung Nyoun Kim, Elizabeth Banasikowska, Sangkyun Lee, Kunyu Wu, Hwa-Yong An, Anthony Mills, Stefan Schneider, U Fritz Bredeek, Daniel R Coulston, Shilei Ding, Andrés Finzi, Meijuan Tian, Katja Klein, Eric J Arts, Jamie F S Mann, Yong Gao, C Yong Kang
BACKGROUND: Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus...
November 28, 2016: Retrovirology
https://www.readbyqxmd.com/read/27879338/functional-interplay-between-murine-leukemia-virus-glycogag-serinc5-and-surface-glycoprotein-governs-virus-entry-with-opposite-effects-on-gammaretroviral-and-ebolavirus-glycoproteins
#18
Yadvinder S Ahi, Shu Zhang, Yashna Thappeta, Audrey Denman, Amin Feizpour, Suryaram Gummuluru, Bjoern Reinhard, Delphine Muriaux, Matthew J Fivash, Alan Rein
: Gammaretroviruses, such as murine leukemia viruses (MLVs), encode, in addition to the canonical Gag, Pol, and Env proteins that will form progeny virus particles, a protein called "glycogag" (glycosylated Gag). MLV glycogag contains the entire Gag sequence plus an 88-residue N-terminal extension. It has recently been reported that glycogag, like the Nef protein of HIV-1, counteracts the antiviral effects of the cellular protein Serinc5. We have found, in agreement with prior work, that glycogag strongly enhances the infectivity of MLVs with some Env proteins but not those with others...
November 22, 2016: MBio
https://www.readbyqxmd.com/read/27879316/structure-based-design-of-cyclically-permuted-hiv-1-gp120-trimers-that-elicit-neutralizing-antibodies
#19
Sannula Kesavardhana, Raksha Das, Michael Citron, Rohini Datta, Linda Ecto, Nonavinakere Seetharam Srilatha, Daniel DiStefano, Ryan Swoyer, Joseph G Joyce, Somnath Dutta, Celia C LaBranche, David C Montefiori, Jessica A Flynn, Raghavan Varadarajan
A major goal for HIV-1 vaccine development is an ability to elicit strong and durable broadly neutralizing antibody (bNAb) responses. The trimeric envelope glycoprotein (Env) spikes on HIV-1 are known to contain multiple epitopes that are susceptible to bNAbs isolated from infected individuals. Nonetheless, all trimeric and monomeric Env immunogens designed to date have failed to elicit such antibodies. We report the structure-guided design of HIV-1 cyclically permuted gp120 that forms homogeneous, stable trimers, and displays enhanced binding to multiple bNAbs, including VRC01, VRC03, VRC-PG04, PGT128, and the quaternary epitope-specific bNAbs PGT145 and PGDM1400...
January 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27871328/membrane-bound-modified-form-of-clade-b-env-jrcsf-is-suitable-for-immunogen-design-as-it-is-efficiently-cleaved-and-displays-all-the-broadly-neutralizing-epitopes-including-v2-and-c2-domain-dependent-conformational-epitopes
#20
Supratik Das, Saikat Boliar, Nivedita Mitra, Sweety Samal, Manish Bansal, Wayne C Koff, Bimal K Chakrabarti
BACKGROUND: Antigenicity of HIV-1 envelope proteins (Envs) of both lab-adapted and primary isolates expressed on the cell surface rarely match with in vitro neutralization of viruses, pseudo-typed with corresponding Envs. Often, both neutralizing and non-neutralizing antibodies bind to Envs expressed on the cell membrane. This could be due to the lack of efficient cleavage of Env expressed on the cell surface. Naturally occurring, efficiently cleaved Envs with appropriate antigenic properties are relatively rare...
November 21, 2016: Retrovirology
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