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https://www.readbyqxmd.com/read/27903913/functional-rnas-combined-assembly-and-packaging-in-vlps
#1
Po-Yu Fang, Lizzette M Gómez Ramos, Stefany Y Holguin, Chiaolong Hsiao, Jessica C Bowman, Hung-Wei Yang, Loren Dean Williams
We describe here a one pot RNA production, packaging and delivery system based on bacteriophage Qβ. We demonstrate a method for production of a novel RNAi scaffold, packaged within Qβ virus-like particles (VLPs). The RNAi scaffold is a general utility chimera that contains a functional RNA duplex with paired silencing and carrier sequences stabilized by a miR-30 stem-loop. The Qβ hairpin on the 5' end confers affinity for the Qβ coat protein (CP). Silencing sequences can include mature miRNAs and siRNAs, and can target essentially any desired mRNA...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27893830/mechanistic-studies-and-modeling-reveal-the-origin-of-differential-inhibition-of-gag-polymorphic-viruses-by-hiv-1-maturation-inhibitors
#2
Zeyu Lin, Joseph Cantone, Hao Lu, Beata Nowicka-Sans, Tricia Protack, Tian Yuan, Hong Yang, Zheng Liu, Dieter Drexler, Alicia Regueiro-Ren, Nicholas A Meanwell, Mark Cockett, Mark Krystal, Max Lataillade, Ira B Dicker
HIV-1 maturation inhibitors (MIs) disrupt the final step in the HIV-1 protease-mediated cleavage of the Gag polyprotein between capsid p24 capsid (CA) and spacer peptide 1 (SP1), leading to the production of infectious virus. BMS-955176 is a second generation MI with improved antiviral activity toward polymorphic Gag variants compared to a first generation MI bevirimat (BVM). The underlying mechanistic reasons for the differences in polymorphic coverage were studied using antiviral assays, an LC/MS assay that quantitatively characterizes CA/SP1 cleavage kinetics of virus like particles (VLPs) and a radiolabel binding assay to determine VLP/MI affinities and dissociation kinetics...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27889616/developments-in-l2-based-human-papillomavirus-hpv-vaccines
#3
REVIEW
Christina Schellenbacher, Richard B S Roden, Reinhard Kirnbauer
Infections with sexually transmitted high-risk Human Papillomavirus (hrHPV), of which there are at least 15 genotypes, are responsible for a tremendous disease burden by causing cervical, and subsets of other ano-genital and oro-pharyngeal carcinomas, together representing 5% of all cancer cases worldwide. HPV subunit vaccines consisting of virus-like particles (VLP) self-assembled from major capsid protein L1 plus adjuvant have been licensed. Prophylactic vaccinations with the 2-valent (HPV16/18), 4-valent (HPV6/11/16/18), or 9-valent (HPV6/11/16/18/31/33/45/52/58) vaccine induce high-titer neutralizing antibodies restricted to the vaccine types that cause up to 90% of cervical carcinomas, a subset of other ano-genital and oro-pharyngeal cancers and 90% of benign ano-genital warts (condylomata)...
November 23, 2016: Virus Research
https://www.readbyqxmd.com/read/27875963/engineering-virus-like-particles-for-antigen-and-drug-delivery
#4
Brett Dallas Hill, Andrew Zak, Eshita Khera, Fei Wen
Virus-like particles (VLPs) are nanoscale biological structures consisting of viral proteins assembled in a morphology that mimics the native virion but do not contain the viral genetic material. The possibility of chemically and genetically modifying the proteins contained within VLPs makes them an attractive system for numerous applications. As viruses are potent immune activators as well as natural delivery vehicles of genetic materials to their host cells, VLPs are especially well suited for antigen and drug delivery applications...
November 22, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27867019/potential-of-rnai-applications-to-control-viral-diseases-of-farmed-shrimp
#5
Ornchuma Itsathitphaisarn, Siripong Thitamadee, Wattana Weerachatyanukul, Kallaya Sritunyalucksana
Viral pathogens pose a primary threat to global shrimp aquaculture. Despite the urgent industry need for them, practical anti-viral control methods are unavailable due, in part, to lack of an adaptive immune response in crustaceans that renders conventional vaccination methods ineffective. One currently studied method of high interest for protecting shrimp against viral infection relies on the post-transcriptional gene silencing mechanism called RNA interference (RNAi) that is induced by gene-specific constructs of double stranded RNA (dsRNA)...
November 17, 2016: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/27866773/influenza-h7n9-lah-hbc-virus-like-particle-vaccine-with-adjuvant-protects-mice-against-homologous-and-heterologous-influenza-viruses
#6
Dan Zheng, Shaoheng Chen, Di Qu, Jianjun Chen, Fuyan Wang, Ran Zhang, Ze Chen
The long alpha-helix (LAH) region located in influenza virus hemagglutinin (HA) shows conservation among different influenza A strains, which could be used as a candidate target of influenza vaccines. Moreover, the hepatitis B virus core protein (HBc) is a carrier for heterologous epitopes in eliciting effective immune responses. We inserted the LAH region of H7N9 influenza virus into the HBc and prepared the LAH-HBc protein, which were capable of self-assembly into virus-like particles (VLP), by using E. coli expression system...
December 12, 2016: Vaccine
https://www.readbyqxmd.com/read/27861835/distinct-t-helper-cell-dependence-of-memory-b-cell-proliferation-versus-plasma-cell-differentiation
#7
Franziska Zabel, Antonia Fettelschoss, Monique Vogel, Pal Johansen, Thomas M Kündig, Martin F Bachmann
Several memory B cell subclasses with distinct functions have been described of which the most effective is the class-switched (CS) memory B cell population. We have previously shown using virus-like particles (VLPs) that the proliferative potential of these CS memory B cells is limited and they fail to re-enter GCs. However, VLP specific memory B cells quickly differentiated into secondary plasma cells (PCs) with a virtue of elevated Ab production compared to primary PCs. Whereas the induction of VLP+ memory B cells was strongly dependent on Th, we were wondering whether re-stimulation of VLP+ memory B cells and their differentiation into secondary PCs would also require Th...
November 9, 2016: Immunology
https://www.readbyqxmd.com/read/27859400/yeast-as-an-expression-system-for-producing-virus-like-particles-what-factors-do-we-need-to-consider
#8
REVIEW
Hyoung Jin Kim, Hong-Jin Kim
The development of various types of virus-like particles (VLPs) has accelerated over the past two decades as the importance of VLPs for generating next-generation vaccines has been appreciated. Yeast has advantages such as scalable fermentation, low risk of contamination by adventitious agents, low production costs and the ability to produce VLPs with reliable qualities. It is generally recognized that yeast is suitable for producing VLPs that have simple structures and are produced intracellularly. However, recently there has been much effort to extend its applicability, and there is now evidence that it can be used as an expression platform for the productions of VLPs not only of non-enveloped viruses but also of enveloped viruses...
November 8, 2016: Letters in Applied Microbiology
https://www.readbyqxmd.com/read/27834623/evaluation-of-the-immunogenicity-of-a-potyvirus-like-particle-as-an-adjuvant-of-a-synthetic-peptide
#9
Albertina Cárdenas-Vargas, Darwin Elizondo-Quiroga, Abel Gutierrez-Ortega, Claudia Charles-Niño, César Pedroza-Roldán
Improvement of current vaccines is highly necessary to increase immunogenicity levels and protection against several pathogens. Virus-like particles (VLPs) are promising approaches for vaccines because they emulate infectious virus structure, but lack any genetic material needed for replication. Plant viruses have emerged as a potential framework for VLP design, mainly because there is no preexisting immunity in mammals. In this study, we evaluated the scaffold of the papaya ringspot virus (PRSV) as a VLP adjuvant for a short synthetic peptide derived from the Hemagglutinin protein of AH1 N1 influenza virus-hemagglutinin (VLP-HA)...
November 11, 2016: Viral Immunology
https://www.readbyqxmd.com/read/27830536/virus-like-particles-derived-from-hiv-1-for-delivery-of-nuclear-proteins-improvement-of-production-and-activity-by-protein-engineering
#10
Marc-André Robert, Viktoria Lytvyn, Francis Deforet, Rénald Gilbert, Bruno Gaillet
Virus-like particles (VLPs) derived from retroviruses and lentiviruses can be used to deliver recombinant proteins without the fear of causing insertional mutagenesis to the host cell genome. In this study we evaluate the potential of an inducible lentiviral vector packaging cell line for VLP production. The Gag gene from HIV-1 was fused to a gene encoding a selected protein and it was transfected into the packaging cells. Three proteins served as model: the green fluorescent protein and two transcription factors-the cumate transactivator (cTA) of the inducible CR5 promoter and the human Krüppel-like factor 4 (KLF4)...
November 9, 2016: Molecular Biotechnology
https://www.readbyqxmd.com/read/27829245/the-true-story-and-advantages-of-rna-phage-capsids-as-nanotools
#11
Paul Pumpens, Regina Renhofa, Andris Dishlers, Tatjana Kozlovska, Velta Ose, Peter Pushko, Kaspars Tars, Elmars Grens, Martin F Bachmann
RNA phages are often used as prototypes for modern recombinant virus-like particle (VLP) technologies. Icosahedral RNA phage VLPs can be formed from coat proteins (CPs) and are efficiently produced in bacteria and yeast. Both genetic fusion and chemical coupling have been successfully used for the production of numerous chimeras based on RNA phage VLPs. In this review, we describe advances in RNA phage VLP technology along with the history of the Leviviridae family, including its taxonomical organization, genomic structure, and important role in the development of molecular biology...
November 10, 2016: Intervirology
https://www.readbyqxmd.com/read/27825348/bacterial-superglue-generates-a-full-length-circumsporozoite-protein-virus-like-particle-vaccine-capable-of-inducing-high-and-durable-antibody-responses
#12
Christoph M Janitzek, Sungwa Matondo, Susan Thrane, Morten A Nielsen, Reginald Kavishe, Steve B Mwakalinga, Thor G Theander, Ali Salanti, Adam F Sander
BACKGROUND: Malaria, caused by Plasmodium falciparum, continues to have a devastating impact on global health, emphasizing the great need for a malaria vaccine. The circumsporozoite protein (CSP) is an attractive target for a malaria vaccine, and forms a major component of RTS,S, the most clinically advanced malaria vaccine. The clinical efficacy of RTS,S has been moderate, yet has demonstrated the viability of a CSP-based malaria vaccine. In this study, a vaccine comprised of the full-length CSP antigen presented on a virus-like particle (VLP) is produced using a split-intein conjugation system (SpyTag/SpyCatcher) and the immunogenicity is tested in mice...
November 8, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27821688/recombinant-dengue-virus-4-envelope-glycoprotein-virus-like-particles-derived-from-pichia-pastoris-are-capable-of-eliciting-homotypic-domain-iii-directed-neutralizing-antibodies
#13
Niyati Khetarpal, Rahul Shukla, Ravi Kant Rajpoot, Ankur Poddar, Meena Pal, Sathyamangalam Swaminathan, Upasana Arora, Navin Khanna
Dengue is a viral pandemic caused by four dengue virus serotypes (DENV-1, 2, 3, and 4) transmitted by Aedes mosquitoes. Reportedly, there has been a 2-fold increase in dengue cases every decade. An efficacious tetravalent vaccine, which can provide long-term immunity against all four serotypes in all target populations, is still unavailable. Despite the progress being made in the live virus-based dengue vaccines, the World Health Organization strongly recommends the development of alternative approaches for safe, affordable, and efficacious dengue vaccine candidates...
November 7, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27814373/involvement-of-an-arginine-triplet-in-m1-matrix-protein-interaction-with-membranes-and-in-m1-recruitment-into-virus-like-particles-of-the-influenza-a-h1n1-pdm09-virus
#14
Adeline Kerviel, Shantoshini Dash, Olivier Moncorgé, Baptiste Panthu, Jan Prchal, Didier Décimo, Théophile Ohlmann, Bruno Lina, Cyril Favard, Etienne Decroly, Michèle Ottmann, Philippe Roingeard, Delphine Muriaux
The influenza A(H1N1)pdm09 virus caused the first influenza pandemic of the 21st century. In this study, we wanted to decipher the role of conserved basic residues of the viral M1 matrix protein in virus assembly and release. M1 plays many roles in the influenza virus replication cycle. Specifically, it participates in viral particle assembly, can associate with the viral ribonucleoprotein complexes and can bind to the cell plasma membrane and/or the cytoplasmic tail of viral transmembrane proteins. M1 contains an N-terminal domain of 164 amino acids with two basic domains: the nuclear localization signal on helix 6 and an arginine triplet (R76/77/78) on helix 5...
2016: PloS One
https://www.readbyqxmd.com/read/27793484/real-time-stability-of-a-hepatitis-e-vaccine-hecolin%C3%A2-demonstrated-with-potency-assays-and-multifaceted-physicochemical-methods
#15
Xiao Zhang, Minxi Wei, Guang Sun, Xin Wang, Min Li, Zhijie Lin, Zhongyi Li, Yufang Li, Mujin Fang, Jun Zhang, Shaowei Li, Ningshao Xia, Qinjian Zhao
The first prophylactic vaccine against hepatitis E virus (HEV), Hecolin®, was licensed in China. Recombinant p239 virus-like particle (VLP) is its active component with dimeric protein as the basic building block harboring the immuno dominant and neutralizing epitopes. The real time and real condition stability of the prefilled syringes for the vaccine was demonstrated using both in vivo mouse potency and in vitro antigenicity assays. A total of 12 lots of Hecolin® were assessed with a set of assays after storage at 2-8°C for 24months...
October 25, 2016: Vaccine
https://www.readbyqxmd.com/read/27723614/late-diagnosis-of-hiv-infection-in-asymptomatic-patients
#16
Mariana A Kundro, Sofie R Terwel, Javier J Toibaro, Guillermo A Viloria, Marcelo H Losso
Recent findings from the START Trial provided evidence that early initiation of antiretroviral treatment should be implemented as the global standard of care. However, a large proportion of patients are still being diagnosed in late stages. Our objective was to evaluate the temporal trend in the CD4+ cell count at diagnosis during a 13 year period and the factors associated with late HIV diagnosis in asymptomatic individuals tested in the Centre for Prevention, Counselling and Diagnosis of our hospital. It was a retrospective study including all asymptomatic patients with new diagnosis of HIV infection...
2016: Medicina
https://www.readbyqxmd.com/read/27689099/rotavirus-recombinant-vp6-nanotubes-act-as-an-immunomodulator-and-delivery-vehicle-for-norovirus-virus-like-particles
#17
Maria Malm, Kirsi Tamminen, Suvi Lappalainen, Timo Vesikari, Vesna Blazevic
We have recently shown that tubular form of rotavirus (RV) recombinant VP6 protein has an in vivo adjuvant effect on the immunogenicity of norovirus (NoV) virus-like particle (VLP) vaccine candidate. In here, we investigated in vitro effect of VP6 on antigen presenting cell (APC) activation and maturation and whether VP6 facilitates NoV VLP uptake by these APCs. Mouse macrophage cell line RAW 264.7 and dendritic cell line JAWSII were used as model APCs. Internalization of VP6, cell surface expression of CD40, CD80, CD86, and major histocompatibility class II molecules, and cytokine and chemokine production were analyzed...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27668597/-the-true-story-and-advantages-of-the-famous-hepatitis-b-virus-core-particles-outlook-2016
#18
P Pumpens, E Grens
This review article is a continuation of the paper "Hepatitis B core particles as a universal display model: a structure-function basis for development" written by Pumpens P. and Grens E., ordered by Professor Lev Kisselev and published in FEBS Letters, 1999, 442, 1-6. The past 17 years have strengthened the paper's finding that the human hepatitis B virus core protein, along with other Hepadnaviridae family member core proteins, is a mysterious, multifunctional protein. The core gene of the Hepadnaviridae genome encodes five partially collinear proteins...
July 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27649319/recent-advancements-in-combination-subunit-vaccine-development
#19
Ming Tan, Xi Jiang
Viral structural proteins share a common nature of homotypic interactions for self-assembling into viral capsids. This natural process has been mimicked in vitro through recombinant technology to generate various virus-like particles (VLPs) and small subviral particles that exhibit similar structural and antigenic properties of their authentic viruses. Therefore, such self-assembled, polyvalent, and highly immunogenic VLPs and small subviral particles are excellent subunit vaccines against individual viruses, such as those against the hepatitis B virus, human papilloma virus, and hepatitis E virus, which have already been in the markets...
September 20, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27648839/hiv-1-vpr-abrogates-the-effect-of-tsg101-overexpression-to-support-virus-release
#20
Nopporn Chutiwitoonchai, Lowela Siarot, Eri Takeda, Tatsuo Shioda, Motoki Ueda, Yoko Aida
HIV-1 budding requires interaction between Gag and cellular TSG101 to initiate viral particle assembly and release via the endosomal sorting complexes required for transport (ESCRT) pathway. However, some reports show that overexpression of TSG101 inhibits virus release by disruption of Gag targeting process. Since a HIV-1 accessory protein, Vpr binds to Gag p6 domain at the position close to the binding site for TSG101, whether Vpr implicates TSG101 overexpression effect has not been investigated. Here, we found that Vpr abrogates TSG101 overexpression effect to rescue viral production...
2016: PloS One
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