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viral nonstructural protein

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https://www.readbyqxmd.com/read/29324359/progress-toward-an-enhanced-vaccine-eight-marked-attenuated-viruses-to-porcine-reproductive-and-respiratory-disease-virus
#1
Allyn Spear, Feng-Xue Wang, Matthew A Kappes, Phani B Das, Kay S Faaberg
Recombinant viruses of strain Ingelvac® PRRS porcine reproductive and respiratory syndrome virus (PRRSV) modified live virus vaccine were produced with two individual small in-frame deletions in nonstructural protein 2 (nsp2; Δ23 and Δ87) and also the same deletions supplanted with foreign tags (Δ23-V5, Δ23-FLAG, Δ23-S, Δ87-V5, Δ87-FLAG, Δ87-S). The viruses, but one (Δ87-FLAG), were stable for 10 passages and showed minimal effects on in vitro growth. Northern hybridization showed that the Δ23-tagged probe detected intracellular viral genome RNA as well as shorter RNAs that may represent heteroclite species, while the Δ87-tagged probe detected predominantly only genome length RNAs...
January 8, 2018: Virology
https://www.readbyqxmd.com/read/29321321/functional-analysis-of-the-dengue-virus-genome-using-an-insertional-mutagenesis-screen
#2
Jeffrey W Perry, Yanhua Chen, Elizabeth Speliotes, Andrew W Tai
In the last few decades, dengue virus, an arbovirus, has spread to over 120 countries. Although a vaccine has been approved in some countries, limitations on its effectiveness, and a lack of effective antiviral treatments reinforce the need for additional research. The functions of several viral nonstructural proteins are essentially unknown. To better understand the functions of these proteins and thus dengue virus pathogenesis, we embarked on a genome wide transposon mutagenesis screen with Next Generation Sequencing to determine sites in the viral genome that tolerate 15 nucleotide insertions...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321319/non-structural-protein-%C3%AF-1s-is-required-for-optimal-reovirus-protein-expression
#3
Matthew B Phillips, Johnasha D Stuart, Emily J Simon, Karl W Boehme
Reovirus non-structural protein σ1s is required for the establishment of viremia and hematogenous viral dissemination. However, the function of the σ1s protein during the reovirus replication cycle is not known. In this study, we found that σ1s was required for efficient reovirus replication in SV40-immortalized endothelial cells (SVECs), mouse embryonic fibroblasts, human umbilical vein endothelial cells (HUVECs), and T84 human colonic epithelial cells. In each of these cell lines, wild type reovirus produced substantially higher viral titers than a σ1s-deficient mutant...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29300893/virus-and-antibody-dynamics-in-travelers-with-acute-zika-virus-infection
#4
Luisa Barzon, Elena Percivalle, Monia Pacenti, Francesca Rovida, Maurizio Zavattoni, Paola Del Bravo, Anna Maria Cattelan, Giorgio Palù, Fausto Baldanti
Background: To improve our understanding of the natural history of Zika virus (ZIKV) infection in humans, we described the dynamics of ZIKV RNA shedding in different body fluids and antibody responses in patients with acute infection. Methods: Twenty-nine adults with travel-associated infection and 1 case of sexual transmission were enrolled and followed up with weekly ZIKV RNA testing in blood, urine, saliva, and semen samples and antibody testing. Results: ZIKV RNA was detected in plasma, urine, and saliva of 57%, 93...
December 30, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29300779/exosomes-serve-as-novel-modes-of-tick-borne-flavivirus-transmission-from-arthropod-to-human-cells-and-facilitates-dissemination-of-viral-rna-and-proteins-to-the-vertebrate-neuronal-cells
#5
Wenshuo Zhou, Michael Woodson, Biswas Neupane, Fengwei Bai, Michael B Sherman, Kyung H Choi, Girish Neelakanta, Hameeda Sultana
Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29297281/suggested-mechanisms-for-zika-virus-causing-microcephaly-what-do-the-genomes-tell-us
#6
Se-Ran Jun, Trudy M Wassenaar, Visanu Wanchai, Preecha Patumcharoenpol, Intawat Nookaew, David W Ussery
BACKGROUND: Zika virus (ZIKV) is an emerging human pathogen. Since its arrival in the Western hemisphere, from Africa via Asia, it has become a serious threat to pregnant women, causing microcephaly and other neuropathies in developing fetuses. The mechanisms behind these teratogenic effects are unknown, although epidemiological evidence suggests that microcephaly is not associated with the original, African lineage of ZIKV. The sequences of 196 published ZIKV genomes were used to assess whether recently proposed mechanistic explanations for microcephaly are supported by molecular level changes that may have increased its virulence since the virus left Africa...
December 28, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29285674/hcv-nonstructural-protein-4-is-associated-with-aggressiveness-features-of-breast-cancer
#7
Abdelfattah M Attallah, Mohamed El-Far, Mohamed A Abdelrazek, Mohamed M Omran, Ashraf Z Mahmoud, Hager S Khalifa, Mohamed M Ahmed, Ibrahim El-Dosoky
BACKGROUND: Hepatitis C virus (HCV) has the lymphotropic feature that is supposed to be the reason of related extrahepatic manifestation. HCV viral oncoproteins may participate in the regulation of some gene expression that has been implicated in tumorigenesis. Our aim is to evaluate the HCV-NS4 circulating levels in breast cancer (BC) and to investigate its relation with BC tumor aggressiveness. METHODS: This study was performed among 158 Egyptian women (120 with BC and 38 with benign breast diseases)...
December 28, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29258862/broad-spectrum-antiviral-activity-of-the-eif4a-inhibitor-silvestrol-against-corona-and-picornaviruses
#8
Christin Müller, Falk W Schulte, Kerstin Lange-Grünweller, Wiebke Obermann, Ramakanth Madhugiri, Stephan Pleschka, John Ziebuhr, Roland K Hartmann, Arnold Grünweller
Coronaviruses (CoV) and picornaviruses are plus-strand RNA viruses that use 5' cap-dependent and cap-independent strategies, respectively, for viral mRNA translation initiation. Here, we analyzed the effects of the plant compound silvestrol, a specific inhibitor of the DEAD-box RNA helicase eIF4A, on viral translation using a dual luciferase assay and virus-infected primary cells. Silvestrol was recently shown to have potent antiviral activity in Ebola virus-infected human macrophages. We found that silvestrol is also a potent and non-toxic inhibitor of cap-dependent viral mRNA translation in CoV-infected human embryonic lung fibroblast (MRC-5) cells...
December 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29230036/negative-charge-and-membrane-tethered-viral-3b-cooperate-to-recruit-viral-rna-dependent-rna-polymerase-3d-pol
#9
Anna Dubankova, Jana Humpolickova, Martin Klima, Evzen Boura
Most single stranded plus RNA viruses hijack phosphatidylinositol 4-kinases (PI4Ks) to generate membranes highly enriched in phosphatidylinositol 4-phosphate (PI4P). These membranous compartments known as webs, replication factories or replication organelles are essential for viral replication because they provide protection from the innate intracellular immune response while serving as platforms for viral replication. Using purified recombinant proteins and biomimetic model membranes we show that the nonstructural viral 3A protein is sufficient to promote membrane hyper-phosphorylation given the proper intracellular cofactors (PI4KB and ACBD3)...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29193300/rna-interference-mediated-knockdown-and-virus-induced-suppression-of-troponin-c-gene-adversely-affect-the-behavior-or-fitness-of-the-green-rice-leafhopper-nephotettix-cincticeps
#10
Hanhong Lan, Xiaojing Hong, Ranran Huang, Xin Lin, Qinghuang Li, Kaihui Li, Tao Zhou
The green rice leafhopper, Nephotettix cincticeps, is a major rice pest in Southeast Asia and Southern China. Novel control strategies must be explored to control the rice pest. Behavior or fitness regulation of insect by modulating the Troponin C (TnC) may be a novel strategy in the comprehensive management of the insect pest. However, characterizations and functions of TnC, especially regarding effect of its RNA interference-mediated gene knockdown on the behavior or fitness of N. cincticeps remain unknown...
November 30, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/29185594/simple-protocol-for-population-sanger-sequencing-for-zika-virus-genomic-regions
#11
Gabriela Bastos Cabral, João Leandro de Paula Ferreira, Renato Pereira de Souza, Mariana Sequetin Cunha, Adriana Luchs, Cristina Adelaide Figueiredo, Luís Fernando de Macedo Brígido
BACKGROUND: A number of Zika virus (ZIKV) sequences were obtained using Next-generation sequencing (NGS), a methodology widely applied in genetic diversity studies and virome discovery. However Sanger method is still a robust, affordable, rapid and specific tool to obtain valuable sequences. OBJECTIVE: The aim of this study was to develop a simple and robust Sanger sequencing protocol targeting ZIKV relevant genetic regions, as envelope protein and nonstructural protein 5 (NS5)...
November 27, 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/29182305/point-of-use-nanobiosensor-for-detection-of-dengue-virus-ns1-antigen-in-adult-aedes-aegypti-a-potential-tool-for-improved-dengue-surveillance
#12
Daniel Aaron Wasik, Ashok Mulchandani, Marylynn V Yates
Dengue virus (DENV) and its primary mosquito vectors Aedes spp., have spread to every continent except Antarctica, causing outbreaks and autochthonous transmission in previously disease-free regions. Recently, the spread of other arboviruses carried by invasive Aedes spp., such as Chikungunya and Zika, seem to be following similar trends as DENV and have renewed interest in monitoring and modelling arboviruses within mosquito vectors. Unfortunately, current commercially available detection methods are designed for the diagnosis of DENV in humans or are too expensive and complex for sustainable monitoring...
November 28, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29175328/construction-of-a-high-yield-dengue-virus-by-replacing-nonstructural-proteins-3-4b-without-increasing-virulence
#13
Supranee Phanthanawiboon, Sabar Pambudi, Magot Diata Omokoko, Keiko Hanabara, Atchareeya A-Nuegoonpipat, Wataru Kamitani, Kazuyoshi Ikuta, Takeshi Kurosu
Producing virus at high yield is critically important for development of whole virion inactivated vaccines or live attenuated vaccines. Most dengue virus (DENV) clinical isolates, however, replicate at low levels in cultured cells, which limits their use for vaccine development. The present study examined differences between low-replicating DENV clinical isolates and high-replicating laboratory strains with the aim of engineering high-yield DENV clinical isolates. Construction of a series of recombinant chimeric viruses derived from a high-replicating laboratory DENV type 4 (DENV-4) H241 strain and a clinical isolate revealed that the NS3-NS4B region of H241 conferred a replication advantage in cultured cells...
November 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29175108/nonstructural-protein-2a-modulates-replication-and-virulence-of-enterovirus-71
#14
Chun Li, Qiao Qiao, Shu-Bin Hao, Zhen Dong, Li Zhao, Jing Ji, Zhi-Yu Wang, Hong-Ling Wen
Enterovirus 71 (EV71) can cause hand, foot, and mouth disease in children, and severe infections can induce neurological complications and even death. However, the pathogenesis of EV71 remains unknown. The 2A proteinase (2Apro) of EV71 plays an important role in segmenting the precursor polyprotein during viral replication, inhibiting host protein synthesis, and evading innate immunity. This study was to determine the function of EV71 2Apro in replication and virulence. A chimeric strain (SDLY 107-2A-1) was recombined by replacing 2Apro of a severe strain (SDLY107) with that of a mild strain (SDLY1) based on an infectious cDNA clone...
November 21, 2017: Virus Research
https://www.readbyqxmd.com/read/29167802/shutdown-of-interferon-signaling-by-a-viral-hijacked-e3-ubiquitin-ligase
#15
COMMENT
Kaitlin A Davis, John T Patton
Viruses manipulate cellular processes to create an environment favorable to replication. For most viruses, this includes subverting the expression of interferon (IFN), a signaling molecule that can stimulate production of a vast array of antiviral gene products. Rotavirus, a segmented double-stranded RNA virus that causes acute gastroenteritis in infants and young children, inhibits IFN expression through its nonstructural protein NSP1. This viral protein stifles IFN expression by inducing the degradation of host factors that are necessary for upregulating the activity of IFN genes...
November 3, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29167346/glycine-zipper-motifs-in-hepatitis-c-virus-nonstructural-protein-4b-are-required-for-the-establishment-of-viral-replication-organelles
#16
David Paul, Vanesa Madan, Omar Ramirez, Maja Bencun, Ina Karen Stoeck, Vlastimil Jirasko, Ralf Bartenschlager
Hepatitis C virus (HCV) RNA replication occurs in tight association with remodeled host cell membranes, presenting as cytoplasmic accumulations of single, double and multi membrane vesicles in infected cells. Formation of these so-called replication organelles is mediated by a complex interplay of host cell factors and viral replicase proteins. Of these, nonstructural protein 4B (NS4B), an integral transmembrane protein, appears to play a key role, but little is known about the molecular mechanisms how this protein contributes to organelle biogenesis...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29162711/expression-and-cleavage-of-middle-east-respiratory-syndrome-coronavirus-nsp3-4-polyprotein-induce-the-formation-of-double-membrane-vesicles-that-mimic-those-associated-with-coronaviral-rna-replication
#17
Diede Oudshoorn, Kevin Rijs, Ronald W A L Limpens, Kevin Groen, Abraham J Koster, Eric J Snijder, Marjolein Kikkert, Montserrat Bárcena
Betacoronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV), are important pathogens causing potentially lethal infections in humans and animals. Coronavirus RNA synthesis is thought to be associated with replication organelles (ROs) consisting of modified endoplasmic reticulum (ER) membranes. These are transformed into double-membrane vesicles (DMVs) containing viral double-stranded RNA and into other membranous elements such as convoluted membranes, together forming a reticulovesicular network...
November 21, 2017: MBio
https://www.readbyqxmd.com/read/29152578/middle-east-respiratory-syndrome-coronavirus-nonstructural-protein-16-is-necessary-for-interferon-resistance-and-viral-pathogenesis
#18
Vineet D Menachery, Lisa E Gralinski, Hugh D Mitchell, Kenneth H Dinnon, Sarah R Leist, Boyd L Yount, Rachel L Graham, Eileen T McAnarney, Kelly G Stratton, Adam S Cockrell, Kari Debbink, Amy C Sims, Katrina M Waters, Ralph S Baric
Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2'O-methyltransferase (2'O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis...
November 2017: MSphere
https://www.readbyqxmd.com/read/29097641/computer-aided-analysis-of-phytochemicals-as-potential-dengue-virus-inhibitors-based-on-molecular-docking-admet-and-dft-studies
#19
Iqra Qaddir, Nouman Rasool, Waqar Hussain, Sajid Mahmood
BACKGROUND & OBJECTIVES: Dengue fever, caused by dengue virus (DENV), has become a serious threat to human lives. Phytochemicals are known to have great potential to eradicate viral, bacterial and fungal-borne diseases in human beings. This study was aimed at in silico drug development against nonstructural protein 4B (NS4B) of dengue virus 4 (DENV4). METHODS: A total of 2750 phytochemicals from different medicinal plants were selected for this study. These plants grow naturally in the climate of Pakistan and India and have been used for the treatment of various pathologies in human for long-time...
July 2017: Journal of Vector Borne Diseases
https://www.readbyqxmd.com/read/29077760/membrane-alterations-induced-by-nonstructural-proteins-of-human-norovirus
#20
Sylvie Y Doerflinger, Mirko Cortese, Inés Romero-Brey, Zach Menne, Thibault Tubiana, Christian Schenk, Peter A White, Ralf Bartenschlager, Stéphane Bressanelli, Grant S Hansman, Volker Lohmann
Human noroviruses (huNoV) are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4) variants. The viral nonstructural (NS) proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far about the ultrastructure of these replication organelles or the contribution of individual NS proteins to their biogenesis. We compared the ultrastructural changes induced by expression of norovirus ORF1 polyproteins with those induced upon infection with murine norovirus (MNV)...
October 2017: PLoS Pathogens
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