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Virus like particle

Andrew G Diamos, Hugh S Mason
Recombinant virus-like particles (VLPs) are proven to be safe and effective vaccine candidates. We have previously described a plant-based recombinant protein expression system based on agroinfiltration of a replicating vector derived from the geminivirus bean yellow dwarf virus (BeYDV). The system has been systematically optimized to improve expression and reduce cell death in Nicotiana benthamiana leaves. Using these modifications, we show that VLPs derived from genotype GII.4 norovirus, the leading cause of acute gastroenteritis worldwide, can be produced at >1 mg/g leaf fresh weight (LFW), over three times the highest level ever reported in plant-based systems...
June 14, 2018: Protein Expression and Purification
Anna Godi, Marianna Martinelli, Mahmoud Haque, Shaowei Li, Qinjian Zhao, Ningshao Xia, Clementina E Cocuzza, Simon Beddows
Background: Naturally-occurring variants of Human papillomavirus (HPV) 58 have been defined as lineages and sublineages but little is known about the impact of this diversity on protein function. We investigate the impact of variation within the major (L1) and minor (L2) capsid proteins of HPV58 on susceptibility to neutralizing antibodies. Methods: Pseudovirus (PsV) representing A1, A2, A3, B1, B2, C, D1 and D2 variants were evaluated for their susceptibility to antibodies elicited during natural infection, preclinical antisera generated against virus-like particles and monoclonal antibodies (MAbs)...
June 13, 2018: Journal of Infectious Diseases
Justin M Choi, Valerie Bourassa, Kevin Hong, Michael Shoga, Elizabeth Lim, Andrew Park, Kazim Apaydin, Andrew K Udit
The potential applications for nanomaterials continue to grow as new materials are developed and environmental and safety concerns are more adequately addressed. Virus-like particles (VLPs) in particular have myriad applications in medicine and biology, exploiting both the reliable, symmetric self-assembly mechanism and the ability to take advantage of surface functionalities that may be appropriately modified through mutation or bioconjugation. Herein we describe the design and application of hybrid VLPs for use as potent heparin antagonists, providing an alternative to the toxic heparin antidote protamine...
June 14, 2018: Molecular Pharmaceutics
Andris Zeltins
Virus-like particle (VLP) technologies are based on virus-inspired artificial structures and the intrinsic ability of viral proteins to self-assemble at controlled conditions. Therefore, the basic knowledge about the mechanisms of viral particle formation is highly important for designing of industrial applications. As an alternative to genetic and chemical processes, different physical methods are frequently used for VLP construction, including well characterized protein complexes for introduction of foreign molecules in VLP structures...
2018: Sub-cellular Biochemistry
Daniel R Beniac, Lindsey L Lamboo, Timothy F Booth
Filoviruses are highly filamentous enveloped animal viruses that can cause severe haemorrhagic fevers. The filovirus ribonucleoprotein forms a highly organized double-layered helical nucleocapsid (NC) containing five different virally encoded proteins. The inner layer consists of NP, the RNA binding protein, complexed with the monopartite linear genome. A distinctive outer layer links individual NP subunits with bridges composed of VP24-VP35 heterodimers, which achieves condensation of the NP-RNA into tight helical coils...
2018: Sub-cellular Biochemistry
Robert R Dourmashkin, Sherman A McCall, Neil Dourmashkin, Matthew J Hannah
Background: In a previous study on encephalitis lethargica, we identified an enterovirus in autopsy brain material. Transmission electron microscopy (TEM), immunohistochemistry (IHC) and molecular analysis were employed.  Our present objective was to investigate, using a similar approach, as to whether virus-like particles (VLP) and enterovirus antigen are present in Parkinson's disease (PD) brainstem neurons. Methods: Fixed tissue from autopsy specimens of late onset PD and control brainstem tissue were received for study...
2018: F1000Research
Gina R Daniel, Caitlin E Pegg, Gregory A Smith
Herpesvirus particles have a complex architecture consisting of an icosahedral capsid that is surrounded by a lipid envelope. Connecting these two components is a layer of tegument that consists of varying amounts of twenty or more proteins. The arrangement of proteins within the tegument cannot easily be assessed and instead is inferred from tegument interactions identified in reductionist models. To better understand the tegument architecture, we have developed an approach to probe capsid-tegument interactions of extracellular viral particles by encoding tobacco etch virus (TEV) protease sites in viral structural proteins, along with distinct fluorescent tags in capsid and tegument components...
June 13, 2018: Journal of Virology
Xuan Guo, Jin-Yi Zhong, Jun-Wen Li
In the twenty-seven years since the discovery of hepatitis C virus (HCV) the majority of individuals exposed to HCV establish a persistent infection, which is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma. In developed nations, the cure rates of HCV infection could be over 90% with direct-acting antiviral (DAA) regimens, which has made the great progress in global eradication. However, the cost of these treatments is so expensive that the patients in developing nations, where the disease burden is the most severe, could not afford it, which highly restricted its access...
June 2018: Journal of Clinical and Experimental Hepatology
Matthieu Legendre, Elisabeth Fabre, Olivier Poirot, Sandra Jeudy, Audrey Lartigue, Jean-Marie Alempic, Laure Beucher, Nadège Philippe, Lionel Bertaux, Eugène Christo-Foroux, Karine Labadie, Yohann Couté, Chantal Abergel, Jean-Michel Claverie
With DNA genomes reaching 2.5 Mb packed in particles of bacterium-like shape and dimension, the first two Acanthamoeba-infecting pandoraviruses remained up to now the most complex viruses since their discovery in 2013. Our isolation of three new strains from distant locations and environments is now used to perform the first comparative genomics analysis of the emerging worldwide-distributed Pandoraviridae family. Thorough annotation of the genomes combining transcriptomic, proteomic, and bioinformatic analyses reveals many non-coding transcripts and significantly reduces the former set of predicted protein-coding genes...
June 11, 2018: Nature Communications
Sergei Popov, Elena Popova, Michio Inoue, Yuanfei Wu, Heinrich Göttlinger
The p2b domain of Rous sarcoma virus (RSV) Gag and the p6 domain of HIV-1 Gag contain late assembly (L) domains that engage the ESCRT membrane fission machinery and are essential for virus release. We now show that the PPXY-type RSV L domain specifically recruits the BAR domain protein PACSIN2 into virus-like particles (VLP), in addition to the NEDD4-like ubiquitin ligase ITCH and ESCRT pathway components such as TSG101. PACSIN2, which has been implicated in the remodeling of cellular membranes and the actin cytoskeleton, is also recruited by HIV-1 p6 independent of its ability to engage the ESCRT factors TSG101 or ALIX...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Zhuo Chen, Stacey T Detvo, Elizabeth Pham, Jeremiah J Gassensmith
The recent rise in virus-like particles (VLPs) in biomedical and materials research can be attributed to their ease of biosynthesis, discrete size, genetic programmability, and biodegradability. While they're highly amenable to bioconjugation reactions for adding synthetic ligands onto their surface, the range in bioconjugation methodologies on these aqueous born capsids is relatively limited. To facilitate the direction of functional biomaterials research, non-traditional bioconjugation reactions must be considered...
May 27, 2018: Journal of Visualized Experiments: JoVE
Peter Pushko, Irina Tretyakova, Rachmat Hidajat, Xiangjie Sun, Jessica A Belser, Terrence M Tumpey
During the past decade, H5N1 highly pathogenic avian influenza (HPAI) viruses have diversified genetically and antigenically, suggesting the need for multiple H5N1 vaccines. However, preparation of multiple vaccines from live H5N1 HPAI viruses is difficult and economically not feasible representing a challenge for pandemic preparedness. Here we evaluated a novel multi-clade recombinant H5N1 virus-like particle (VLP) design, in which H5 hemagglutinins (HA) and N1 neuraminidase (NA) derived from four distinct clades of H5N1 virus were co-localized within the VLP structure...
June 6, 2018: Vaccine
Nayeli Aguilar-Hernández, Susana López, Carlos F Arias
Human astrovirus is an important etiological agent of acute gastroenteritis in young children. Despite advances in the characterization of the structure of the virion by cryo-electron microscopy and of capsid proteins by x-ray crystallography, the definition of the minimal polypeptide composition of infectious virus particles has been elusive. In this work we show that mature infectious particles are composed by only two proteins; VP34 that forms the core domain of the virus, and VP27 that constitutes the 30 dimeric spikes present on the virus surface...
June 5, 2018: Virology
Vishal M Toprani, Yuan Cheng, Newton Wahome, Harshit Khasa, Lisa A Kueltzo, Richard M Schwartz, C Russell Middaugh, Sangeeta B Joshi, David B Volkin
The zoonotic equine encephalitis viruses (EEV) can cause debilitating and life-threatening disease, leading to ongoing vaccine development efforts for an effective virus-like particle (VLP) vaccine based on three strains of EEV (Eastern, Western and Venezuelan or EEE, WEE and VEE VLPs, respectively). In this work, TEM and light scattering studies showed enveloped, spherical, and ∼70 nm sized VLPs. Biophysical studies demonstrated optimal VLP physical stability in the pH range of 7.5-8.5 and at temperatures below ∼50o C...
June 5, 2018: Journal of Pharmaceutical Sciences
Kuniaki Nerome, Ryoji Yamaguchi, Naoyuki Fuke, Uda Zahli Izzati, Kenichi Maegawa, Shigeo Sugita, Kazunori Kawasaki, Kazumichi Kuroda, Reiko Nerome
To counter the spread of multiple Japanese encephalitis virus (JEV) variants harboured in alternative host species and highly neurotoxic variants with new antigenicity, such as genotype V (Muar), methods for developing more effective and low-cost vaccines against a variety of epidemic JEV strains are required. Here, we successfully synthesized large amounts of a Muar virus-like particle (MVLP) vaccine for JEV in silkworm pupae by using a Bombyx mori nuclear polyhedrosis virus recombinant consisting of JEV codon-optimized envelope (E) DNA...
June 7, 2018: Journal of General Virology
Fiona D Barr, Christina Ochsenbauer, Charles R Wira, Marta Rodriguez-Garcia
Women acquire human immunodeficiency virus (HIV) mainly through sexual intercourse. However, low transmission rates per sexual act indicate that local immune mechanisms contribute to HIV prevention. Neutrophils represent 10-20% of the genital immune cells in healthy women. Neutrophils mediate mucosal protection against bacterial and fungal pathogens through different mechanisms, including the release of neutrophil extracellular traps (NETs). NETs are DNA fragments associated with antimicrobial granular proteins...
June 6, 2018: Mucosal Immunology
Rachel B Brouillette, Elisabeth K Phillips, Radhika Patel, Wadie Mahauad-Fernandez, Sven Moller-Tank, Kai J Rogers, Jacob A Dillard, Ashley L Cooney, Luis Martinez-Sobrido, Chioma Okeoma, Wendy Maury
Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year. LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor, α-dystroglycan (αDG). Yet, cells lacking αDG are permissive to LASV infection, suggesting that alternative receptors exist. Previous studies demonstrate that phosphatidylserine (PtdSer)-binding receptors, Axl and Tyro3 along with C-type lectin receptors, mediate αDG-independent entry...
June 6, 2018: Journal of Virology
Sarah Moeschler, Samira Locher, Gert Zimmer
Cellular kinases are crucial for the transcription/replication of many negative-strand RNA viruses and might serve as targets for antiviral therapy. In this study, a library comprising 80 kinase inhibitors was screened for antiviral activity against vesicular stomatitis virus (VSV), a prototype member of the family Rhabdoviridae . 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125), an inhibitor of eukaryotic elongation factor 2 (eEF2) kinase, significantly inhibited entry of single-cycle VSV encoding a luciferase reporter...
June 5, 2018: Viruses
Kazunori Matsuura
This feature article describes recent progress in synthetic strategies to construct viral capsid-like spherical nanomaterials using the self-assembly of peptides and/or proteins. By mimicking the self-assembly of spherical viral capsids and clathrin, trigonal peptide conjugates bearing β-sheet-forming peptides, glutathiones, or coiled-coil-forming peptides were developed to construct viral capsid-like particles. β-Annulus peptides from tomato bushy stunt virus self-assembled into viral capsid-like nanocapsules with a size of 30-50 nm, which could encapsulate various guest molecules and be decorated with different molecules on their surface...
June 6, 2018: Chemical Communications: Chem Comm
Ravi Kant Rajpoot, Rahul Shukla, Upasana Arora, Sathyamangalam Swaminathan, Navin Khanna
Dengue is a significant public health problem worldwide, caused by four antigenically distinct mosquito-borne dengue virus (DENV) serotypes. Antibodies to any given DENV serotype which can afford protection against that serotype tend to enhance infection by other DENV serotypes, by a phenomenon termed antibody-dependent enhancement (ADE). Antibodies to the viral pre-membrane (prM) protein have been implicated in ADE. We show that co-expression of the envelope protein of all four DENV serotypes, in the yeast Pichia pastoris, leads to their co-assembly, in the absence of prM, into tetravalent mosaic VLPs (T-mVLPs), which retain the serotype-specific antigenic integrity and immunogenicity of all four types of their monomeric precursors...
June 5, 2018: Scientific Reports
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