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https://www.readbyqxmd.com/read/28546913/genetic-assembly-of-double-layered-fluorescent-protein-nanoparticles-for-cancer-targeting-and-imaging
#1
Seong-Eun Kim, Sung Duk Jo, Koo Chul Kwon, You-Yeon Won, Jeewon Lee
Hepatitis B virus capsid (HBVC), a self-assembled protein nanoparticle comprised of 180 or 240 subunit proteins, is used as a cage for genetic encapsulation of fluorescent proteins (FPs). The self-quenching of FPs is controlled by varying the spacing between FPs within the capsid structure. Double-layered FP nanoparticle possessing cancer cell-targeting capabilities is also produced by additionally attaching FPs and cancer cell receptor-binding peptides (affibodies) to the outer surface of the capsid. The generically modified HBVC with double layers of mCardinal FPs and affibodies (mC-DL-HBVC) exhibit a high fluorescence intensity and a strong photostability, and is efficiently internalized by cancer cells and significantly stable against intracellular degradation...
May 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28544850/pcpp-adjuvanted-respiratory-syncytial-virus-rsv-sf-subunit-vaccine-self-assembled-supramolecular-complexes-enable-enhanced-immunogenicity-and-protection
#2
Corinne Cayatte, Alexander Marin, Gaurav Manohar Rajani, Kirsten Schneider-Ohrum, Angie Snell Bennett, Jason D Marshall, Alexander K Andrianov
PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the post-fusion glycoprotein (RSV sF) of RSV, which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulations induce high neutralization titers to RSV comparable to Alum formulations even at a low PCPP dose and protect animals against viral challenge both in the lung and upper respiratory tract. PCPP formulations were also characterized by Th1-biased responses, compared to Th2-biased responses that are more typical for RSV sF alone or RSV sF-Alum formulations, suggesting an inherent immunostimulating activity of the polyphosphazene adjuvant...
May 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28542609/potent-and-selective-inhibition-of-pathogenic-viruses-by-engineered-ubiquitin-variants
#3
Wei Zhang, Ben A Bailey-Elkin, Robert C M Knaap, Baldeep Khare, Tim J Dalebout, Garrett G Johnson, Puck B van Kasteren, Nigel J McLeish, Jun Gu, Wenguang He, Marjolein Kikkert, Brian L Mark, Sachdev S Sidhu
The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses...
May 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542478/structural-basis-of-nectin-1-recognition-by-pseudorabies-virus-glycoprotein-d
#4
An Li, Guangwen Lu, Jianxun Qi, Lili Wu, Kegong Tian, Tingrong Luo, Yi Shi, Jinghua Yan, George F Gao
An early and yet indispensable step in the alphaherpesvirus infection is the engagement of host receptors by the viral envelope glycoprotein D (gD). Of the thus-far identified gD receptors, nectin-1 is likely the most effective in terms of its wide usage by multiple alphaherpesviruses for cell entry. The molecular basis of nectin-1 recognition by the gD protein is therefore an interesting scientific question in the alphaherpesvirus field. Previous studies focused on the herpes simplex virus (HSV) of the Simplexvirus genus, for which both the free gD structure and the gD/nectin-1 complex structure were reported at high resolutions...
May 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28539733/molecular-docking-of-phytoligands-to-the-viral-protein-receptor-p-monodon-rab7
#5
Jerrine Joseph, Raj Bhaskaran, Muthusamy Kaliraj, Muthiyah Muthuswamy, Arumugam Suresh
The development of shrimp aquaculture has been severely affected by viral diseases resulting in a huge economic burden to the industry. White spot disease (WSD) has caused severe mortality in farmed shrimp in many countries. Globally aquaculture industries face huge economic losses due to rapid spread of White Spot Syndrome Virus (WSSV) disease that can cause 100% mortality in a short period of 3-10 days. In the present study in order to prevent the spread of WSSV disease in shrimps, the receptor, PmRab7 has been chosen as the drug target...
2017: Bioinformation
https://www.readbyqxmd.com/read/28539455/functional-consequences-of-rna-5-terminal-deletions-on-coxsackievirus-b3-rna-replication-and-ribonucleoprotein-complex-formation
#6
Nicolas Lévêque, Magali Garcia, Alexis Bouin, Joseph H C Nguyen, Genevieve P Tran, Laurent Andreoletti, Bert L Semler
Group B coxsackieviruses are responsible for chronic cardiac infections. However, the molecular mechanisms by which the virus can persist in the human heart long after the signs of acute myocarditis have abated are still not completely understood. Recently, coxsackievirus B3 strains with 5' terminal deletions in genomic RNAs were isolated from a patient suffering from idiopathic dilated cardiomyopathy, suggesting that such mutant viruses may be the forms responsible for persistent infection. These deletions lacked portions of 5' stem-loop I, which is an RNA secondary structure required for viral RNA replication...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539454/ebola-virus-delta-peptide-is-a-viroporin
#7
Jing He, Lilia I Melnik, Alexander Komin, Gregory Wiedman, Taylor Fuselier, Cameron F Morris, Charles G Starr, Peter C Searson, William R Gallaher, Kalina Hristova, Robert F Garry, William C Wimley
The Ebola virus (EBOV) genome encodes for a partly conserved, 40-residue, nonstructural polypeptide, called the delta peptide, which is produced in abundance during Ebola virus disease. The function of the delta peptide is unknown, but sequence analysis has suggested that delta peptide could be a viroporin, belonging to a diverse family of membrane-permeabilizing small polypeptides involved in replication and pathogenesis of numerous viruses. Full length and conserved C-terminal delta peptide fragments permeabilize the plasma membranes of nucleated cells of rodent, dog, monkey and human origin, increase ion permeability across confluent cell monolayers and permeabilize synthetic lipid bilayers...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539452/interactions-between-hiv-1-gag-and-viral-rna-genome-enhance-virion-assembly
#8
Kari A Dilley, Olga A Nikolaitchik, Andrea Galli, Ryan C Burdick, Louis Levine, Kelvin Li, Alan Rein, Vinay K Pathak, Wei-Shau Hu
Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539446/infectious-prions-in-the-pregnancy-microenvironment-of-cwd-infected-reeves-muntjac-deer
#9
Amy V Nalls, Erin McNulty, Clare E Hoover, Laura A Pulscher, Edward A Hoover, Candace K Mathiason
Ample evidence exists for the presence of infectious agents at the maternal-fetal interface, often with grave outcomes to the developing fetus (i.e. zika virus, brucella, cytomegalovirus, toxoplasma). While less studied, pregnancy-related transmissible spongiform encephalopathies (TSEs) have been implicated in several species, including humans. Our previous work has shown that prions can be transferred from mother-to-offspring resulting in the development of clinical TSE disease in offspring born to CWD-infected muntjac dams (64)...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539441/chikungunya-virus-overcomes-polyamine-depletion-by-mutation-of-nsp1-and-the-opal-stop-codon-to-confer-enhanced-replication-and-fitness
#10
Bryan C Mounce, Teresa Cesaro, Lea Vlajnić, Anna Vidiņa, Thomas Vallet, James Weger-Lucarelli, Gabriella Pasoni, Kenneth A Stapleford, Jean-Pierre Levraud, Marco Vignuzzi
Polyamines, small positively-charge molecules present in all cells, play important roles in the replication of DNA and RNA viruses. Chikungunya virus (CHIKV) relies on polyamines for translation of the viral genome upon viral entry, and pharmacological depletion of polyamines limits viral replication. However, the potential development of antiviral resistance necessitates a better understanding of how polyamines function and can be targeted via compounds that alter polyamine levels. We have isolated CHIKV that is resistant to polyamine depletion that contains two mutations in the non-structural protein 1 (nsP1) coding region in combination with mutation to the opal stop codon preceding nsP4...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539440/uncovering-the-repertoire-of-endogenous-flaviviral-elements-in-aedes-mosquito-genomes
#11
Yasutsugu Suzuki, Lionel Frangeul, Laura B Dickson, Hervé Blanc, Yann Verdier, Joelle Vinh, Louis Lambrechts, Maria-Carla Saleh
Endogenous viral elements derived from non-retroviral RNA viruses were described in various animal genomes. Whether they have a biological function such as host immune protection against related viruses is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in Aedes mosquitoes, the vectors of arboviruses such as dengue and chikungunya viruses. Previous studies identified three EFVEs from Ae. albopictus and one from Ae. aegypti cell lines. However, in-depth characterization of EFVEs in wild-type mosquito populations and individuals in vivo has not been performed...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28538165/the-complexity-in-herpesvirus-entry
#12
REVIEW
Karthik Sathiyamoorthy, Jia Chen, Richard Longnecker, Theodore S Jardetzky
Enveloped viruses have evolved diverse transmembrane proteins and protein complexes to enable host cell entry by regulating and activating membrane fusion in a target cell-specific manner. In general terms, the entry process requires a receptor binding step, an activation step and a membrane fusion step, which can be encoded within a single viral protein or distributed among multiple viral proteins. HIV and influenza virus, for example, encode all of these functions in a single trimeric glycoprotein, HIV env or influenza virus hemagglutinin (HA)...
May 21, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28537245/-impact-of-mutations-in-nucleoprotein-on-replication-of-influenza-virus-a-hong-kong-1-68-162-35-reassortants-at-different-temperatures
#13
A A Pulkina, M V Sergeeva, S V Petrov, A V Fadeev, A B Komissarov, E A Romanovskaya-Romanko, M V Potapchuk, L M Tsybalova
The nucleoprotein (NP) of influenza virus is a multifunctional RNA binding protein. The role of NP in the adaptation of influenza viruses to a host has been experimentally proved. Ambiguous data are available on the role of nucleoprotein in the attenuation of influenza A viruses, which is characterized by ability to replicate at low temperature (26°C) and inability to replicate at high temperature (39°C). Influenza virus donor strain A/Hong Kong/1/68/162/35 (H3N2), adapted to growth at low temperature, differs from the wild type virus by 14 amino acid mutations in the internal and non-structural proteins...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28537239/-translational-efficiency-of-bvdv-ires-and-emcv-ires-for-t7-rna-polymerase-driven-cytoplasmic-expression-in-mammalian-cell-lines
#14
F Ghassemi, O Madadgar, F Roohvand, M Rasekhian, M H Etemadzadeh, G R N Boroujeni, A G Langroudi, K Azadmanesh
Mammalian T7 polymerase-based cytoplasmic expression systems are common tool for molecular studies. The majority of these systems include the internal ribosome entry site (IRES) of the encephalomyocarditis virus (EMCV). To carry out a cap-independent translation process, this type of IRES might require the expression of an extensive array of host factors, what is a disadvantage. Other IRESes might be less dependent on the host cell factors, but their biology is characterized to a lesser degree. Here, we compare the translational efficiencies of bovine viral diarrhea virus (BVDV) IRES with that of ECMV...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28537193/isolated-potato-virus-a-coat-protein-possesses-unusual-properties-and-forms-different-short-virus-like-particles
#15
Alexander L Ksenofontov, Eugeny N Dobrov, Natalia V Fedorova, Marina V Serebryakova, Andrei N Prusov, Ludmila A Baratova, Viiu Paalme, Lilian Järvekülg, Eleonora V Shtykova
In our previous study, we have observed that the isolated coat proteins (CP) of the Potyvirus Potato Virus A (PVA) virions exhibit an intrinsic tendency of to self-associate into various multimeric forms containing some fractions of cross-β-structure. In this report, we studied the effect of solution conditions on the structure and dissociation of isolated PVA CP using a number of complementary physicochemical methods. Analysis of the structure of PVA CP in solution was performed by limited proteolysis with MALDI-TOF Mass Spectrometry analysis, transmission electron microscopy, intrinsic fluorescence spectroscopy and synchrotron small angle X-ray scattering (SAXS)...
May 24, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28536674/anti-idiotypic-antibodies-specific-to-prm-monoantibody-prevent-antibody-dependent-enhancement-of-dengue-virus-infection
#16
Miao Wang, Fan Yang, Dana Huang, Yalan Huang, Xiaomin Zhang, Chao Wang, Shaohua Zhang, Renli Zhang
Dengue virus (DENV) co-circulates as four serotypes (DENV1-4). Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody dependent enhancement (ADE). Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM) of DENV...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28535993/structural-basis-for-asymmetric-conductance-of-the-influenza-m2-proton-channel-investigated-by-solid-state-nmr-spectroscopy
#17
Venkata S Mandala, Shu Yu Liao, Byungsu Kwon, Mei Hong
The influenza M2 protein forms an acid-activated proton channel that is essential for virus replication. The transmembrane H37 selects for protons under low external pH (pHout) while W41 ensures proton conduction only from the N-terminus to the C-terminus and prevents reverse current under low internal pH (pHin). Here we address the molecular basis for this asymmetric conduction by investigating the structure and dynamics of a mutant channel, W41F, which permits reverse current under low pHin. Solid-state NMR experiments show that W41F M2 retains the pH-dependent α-helical conformations and tetrameric structure of the wild-type channel, but has significantly altered protonation and tautomeric equilibria at H37...
May 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28535337/overall-structural-model-of-ns5a-protein-from-hepatitis-c-virus-and-modulation-by-mutations-confering-resistance-of-virus-replication-to-cyclosporin-a
#18
Aurelie Badillo, Veronique Brechot, Stephane Sarrazin, François-Xavier Cantrelle, Frederic Delolme, Marie-Laure Fogeron, Jennifer Molle, Roland Montserret, Anja Bockmann, Ralf Bartenschlager, Volker Lohmann, Guy Lippens, Sylvie Ricard-Blum, Xavier Hanoulle, Francois Penin
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a RNA-binding phosphoprotein composed of a N-terminal membrane anchor (AH), a structured domain 1 (D1) and two intrinsically disordered domains (D2 and D3). The knowledge of the functional architecture of this multifunctional protein remains limited. We report here that NS5A-D1D2D3 produced in a wheat germ cell-free system is obtained under a highly phosphorylated state. Its NMR analysis revealed that these phosphorylations do not change the disordered nature of D2 and D3 domains but increase the number of conformers due to partial phosphorylations...
May 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28534849/evaluation-and-comparison-of-the-pathogenicity-and-host-immune-responses-induced-by-a-g2b-taiwan-porcine-epidemic-diarrhea-virus-strain-pintung-52-and-its-highly-cell-culture-passaged-strain-in-conventional-5-week-old-pigs
#19
Yen-Chen Chang, Chi-Fei Kao, Chia-Yu Chang, Chian-Ren Jeng, Pei-Shiue Tsai, Victor Fei Pang, Hue-Ying Chiou, Ju-Yi Peng, Ivan-Chen Cheng, Hui-Wen Chang
A genogroup 2b (G2b) porcine epidemic diarrhea virus (PEDV) Taiwan Pintung 52 (PEDVPT) strain was isolated in 2014. The pathogenicity and host antibody responses elicited by low-passage (passage 5; PEDVPT-P5) and high-passage (passage 96; PEDVPT-P96) PEDVPT strains were compared in post-weaning PEDV-seronegative pigs by oral inoculation. PEDVPT-P5-inoculation induced typical diarrhea during 1-9 days post inoculation with fecal viral shedding persisting for 26 days. Compared to PEDVPT-P5, PEDVPT-P96 inoculation induced none-to-mild diarrhea and lower, delayed fecal viral shedding...
May 19, 2017: Viruses
https://www.readbyqxmd.com/read/28534504/crystal-structure-of-the-receptor-binding-domain-of-the-spike-glycoprotein-of-human-betacoronavirus-hku1
#20
Xiuyuan Ou, Hongxin Guan, Bo Qin, Zhixia Mu, Justyna A Wojdyla, Meitian Wang, Samuel R Dominguez, Zhaohui Qian, Sheng Cui
Human coronavirus (CoV) HKU1 is a pathogen causing acute respiratory illnesses and so far little is known about its biology. HKU1 virus uses its S1 subunit C-terminal domain (CTD) and not the N-terminal domain like other lineage A β-CoVs to bind to its yet unknown human receptor. Here we present the crystal structure of HKU1 CTD at 1.9 Å resolution. The structure consists of three subdomains: core, insertion and subdomain-1 (SD-1). While the structure of the core and SD-1 subdomains of HKU1 are highly similar to those of other β-CoVs, the insertion subdomain adopts a novel fold, which is largely invisible in the cryo-EM structure of the HKU1 S trimer...
May 23, 2017: Nature Communications
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