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https://www.readbyqxmd.com/read/28345656/structure-and-function-of-the-zika-virus-full-length-ns5-protein
#1
Baoyu Zhao, Guanghui Yi, Fenglei Du, Yin-Chih Chuang, Robert C Vaughan, Banumathi Sankaran, C Cheng Kao, Pingwei Li
The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28344409/outbreak-of-foot-and-mouth-disease-and-peste-des-petits-ruminants-in-sheep-flock-imported-for-immediate-slaughter-in-riyadh
#2
M A Mahmoud, S A Galbat
AIM: To detect and identify the causative agent or agents of the following clinical symptoms which were fever, lack of appetite, salivation, vesiculation, erosions of the buccal mucosa, nose, and feet. The signs vary from mild to severe. The mortality rate of the disease is high. The morbidity rate reaches up to 100%. Sheep also show bloody diarrhea and rapid respiration. Sheep flock resident in El-Kharje Governorate. MATERIALS AND METHODS: A total of 50 serum samples and 50 buffy coat samples were collected from Marino sheep flock suffered from high mortalities, fever, lameness, diarrhea, stomatitis, and respiratory distress...
February 2017: Veterinary World
https://www.readbyqxmd.com/read/28343379/hepatitis-c-virus-nonstructural-5a-protein-hcv-ns5a-inhibits-hepatocyte-apoptosis-through-the-nf-kappab-mir-503-bcl-2-pathway
#3
Xie Zheng Yuan, Xiao Zhi Hua, Wang Fen Fen
The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus (HCV) RNA genome is a multifunctional phosphoprotein. To analyse the influence of NS5A on apoptosis, we established an Hep-NS5A cell line (HepG2 cells that stably express NS5A) and induced apoptosis using tumour necrosis factor (TNF)-alpha. We utilised the MTT assay to detect cell viability, real-time quantitative polymerase chain reaction and Western blot to analyse gene and protein expression, and a luciferase reporter gene experiment to investigate the targeted regulatory relationship...
March 27, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28341934/molecular-chaperone-jiv-promotes-the-rna-replication-of-classical-swine-fever-virus
#4
Kangkang Guo, Haimin Li, Xuechao Tan, Mengmeng Wu, Qizhuang Lv, Wei Liu, Yanming Zhang
The nonstructural protein 2 (NS2) of classical swine fever virus (CSFV) is a self-splicing ribozyme wherein the precursor protein NS2-3 is cleaved, and the cleavage efficiency of NS2-3 is crucial to the replication of viral RNA. However, the proteolytic activity of NS2 autoprotease may be achieved through a cellular chaperone called J-domain protein interacting with viral protein (Jiv) or its fragment Jiv90, as evidence suggests that Jiv is required for the proper functioning of the NS2 protein of bovine viral diarrhea virus...
March 24, 2017: Virus Genes
https://www.readbyqxmd.com/read/28303345/detection-and-characterization-of-hepatitis-a-virus-circulating-in-egypt
#5
Hazem Hamza, Dina Nadeem Abd-Elshafy, Sayed A Fayed, Mahmoud Mohamed Bahgat, Nagwa Abass El-Esnawy, Emam Abdel-Mobdy
Hepatitis A virus (HAV) still poses a considerable problem worldwide. In the current study, hepatitis A virus was recovered from wastewater samples collected from three wastewater treatment plants over one year. Using RT-PCR, HAV was detected in 43 out of 68 samples (63.2%) representing both inlet and outlet. Eleven positive samples were subjected to sequencing targeting the VP1-2A junction region. Phylogenetic analysis revealed that all samples belonged to subgenotype IB with few substitutions at the amino acid level...
March 16, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28291746/crystal-structure-of-full-length-zika-virus-ns5-protein-reveals-a-conformation-similar-to-japanese-encephalitis-virus-ns5
#6
Anup K Upadhyay, Matthew Cyr, Kenton Longenecker, Rakesh Tripathi, Chaohong Sun, Dale J Kempf
The rapid spread of the recent Zika virus (ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 of Zika virus (ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3...
March 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28288679/muscovy-duck-reovirus-%C3%AF-ns-protein-triggers-autophagy-enhancing-virus-replication
#7
Yijian Wu, Longping Cui, Erpeng Zhu, Wuduo Zhou, Quanxi Wang, Xiaoping Wu, Baocheng Wu, Yifan Huang, Hung-Jen Liu
BACKGROUND: Muscovy duck reovirus (MDRV) causes high morbidity and mortality in Muscovy ducklings at 10 days old and can persist in an infected flock until the ducklings of 6 weeks old. It shares common physicochemical properties with avian reovirus (ARV) and differs in coding assignment and pathogenicity. The ARV p17 protein has been shown to trigger autophagy via activation multiple signaling pathways, which benefits virus replication. Since MDRV lacks the p17 protein, whether and how MDRV induces autophagy remains unknown...
March 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/28283039/hepatitis-c-virus-ns3-protein-enhances-hepatocellular-carcinoma-cell-invasion-by-promoting-ppm1a-ubiquitination-and-degradation
#8
Yali Zhou, Yan Zhao, Yaoying Gao, Wenjun Hu, Yan Qu, Ning Lou, Ying Zhu, Xiaoping Zhang, Hongmei Yang
BACKGROUND: Growing evidence suggests that hepatitis C virus (HCV) contributes to hepatocellular carcinoma (HCC) by directly modulating oncogenic signaling pathways. Protein phosphatase magnesium-dependent 1A (PPM1A) has recently emerged as an important tumor suppressor as it can block a range of tumor-centric signaling pathways through protein dephosphorylation. However, the role and regulatory mechanisms of PPM1A in HCV-infected cells have not been reported. METHODS: Total, cytoplasmic, and nuclear PPM1A protein after HCV infection or overexpression of HCV nonstructural protein 3 (NS3) were detected by western blotting...
March 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28280374/optimizing-choice-of-oral-interferon-free-treatment-for-genotype-1-hepatitis-c-virus-using-testing-for-ns5a-resistance-a-cost-utility-analysis-from-the-perspective-of-the-italian-national-health-service
#9
Kirsten Y Westerhout, Walter Bouwmeester, Inge Duchesne, Marta Pisini, Marjanne A Piena, Francesco Damele, Beatrice Gueron, Maarten Treur, Jonathan Belsey
BACKGROUND: Patients with genotype-1 hepatitis C virus infection who have failed to respond to standard therapy or who relapse following treatment may be considered for an interferon-free regimen incorporating a nonstructural protein 5A (NS5A) inhibitor. Sustained virologic response (SVR) with these regimens is typically >90%, but this is reduced in patients with NS5A resistance. European Association for Study of the Liver guidelines recommend simeprevir + sofosbuvir ± ribavirin (SMV+SOF±R) for re-treating patients failing an NS5A inhibitor-containing regimen...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28263312/diagnosis-of-zika-virus-infection-on-a-nanotechnology-platform
#10
Bo Zhang, Benjamin A Pinsky, Jeyarama S Ananta, Su Zhao, Shylaja Arulkumar, Hao Wan, Malaya K Sahoo, Janaki Abeynayake, Jesse J Waggoner, Clay Hopes, Meijie Tang, Hongjie Dai
We developed a multiplexed assay on a plasmonic-gold platform for measuring IgG and IgA antibodies and IgG avidity against both Zika virus (ZIKV) and dengue virus (DENV) infections. In contrast to IgM cross-reactivity, IgG and IgA antibodies against ZIKV nonstructural protein 1 (NS1) antigen were specific to ZIKV infection, and IgG avidity revealed recent ZIKV infection and past DENV-2 infection in patients in dengue-endemic regions. This assay could enable specific diagnosis of ZIKV infection over other flaviviral infections...
March 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28257598/structural-basis-for-dimerization-and-rna-binding-of-avian-infectious-bronchitis-virus-nsp9
#11
Tingting Hu, Cheng Chen, Huiyan Li, Yanshu Dou, Ming Zhou, Deren Lu, Qi Zong, Yulei Li, Cheng Yang, Zhihui Zhong, Namit Singh, Honggang Hu, Rundong Zhang, Haitao Yang, Dan Su
The potential for infection by coronaviruses (CoVs) has become a serious concern with the recent emergence of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) in the human population. CoVs encode two large polyproteins, which are then processed into 15-16 nonstructural proteins (nsps) that make significant contributions to viral replication and transcription by assembling the RNA replicase complex. Among them, nsp9 plays an essential role in viral replication by forming a homodimer that binds single-stranded RNA...
March 3, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28256607/the-rotavirus-nsp4-viroporin-domain-is-a-calcium-conducting-ion-channel
#12
Thieng Pham, Jacob L Perry, Timothy L Dosey, Anne H Delcour, Joseph M Hyser
Viroporins are small virus-encoded ion channel proteins. Most viroporins are monovalent selective cation channels, with few showing the ability to conduct divalent cations, like calcium (Ca(2+)). Nevertheless, some viroporins are known to disrupt host cell Ca(2+) homeostasis, which is critical for virus replication and pathogenesis. Rotavirus nonstructural protein 4 (NSP4) is an endoplasmic reticulum transmembrane glycoprotein that has a viroporin domain (VPD), and NSP4 viroporin activity elevates cytosolic Ca(2+) in mammalian cells...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28250121/porcine-deltacoronavirus-nsp5-antagonizes-type-i-interferon-signaling-by-cleaving-stat2
#13
Xinyu Zhu, Dang Wang, Junwei Zhou, Ting Pan, Jiyao Chen, Yuting Yang, Mengting Lv, Xu Ye, Guiqing Peng, Liurong Fang, Shaobo Xiao
Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus. The first outbreak of PDCoV was announced from the United States in 2014, followed by reports in Asia. The nonstructural protein nsp5 is a 3C-like protease of coronavirus and our previous study showed that PDCoV nsp5 inhibits type I interferon (IFN) production. In this study, we found that PDCoV nsp5 significantly inhibited IFN-stimulated response element (ISRE) promoter activity and transcription of IFN-stimulated genes (ISGs), suggesting that PDCoV nsp5 also suppresses IFN signaling...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28245093/novel-nucleoside-analogues-targeting-hcv-replication-through-an-ns5a-dependent-inhibition-mechanism
#14
Nikolaos Lougiakis, Efseveia Frakolaki, Panagiota Karmou, Nicole Pouli, Panagiotis Marakos, Vanesa Madan, Ralf Bartenschlager, Niki Vassilaki
A series of new tricyclic nucleosides were synthesized and evaluated as Hepatitis C virus (HCV) replication inhibitors. Initial screening in a HCV replicon system, derived from a genotype 1b isolate, identified 9-benzylamino-3-(β-D-ribofuranosyl)-3H-imidazo[4',5':5,6]pyrido[2,3-b]pyrazine (15d) as the most potent analogue. Comparative assessment of 15d activity against HCV full-length viruses or subgenomic replicons derived from genotype 1 - 4 revealed a specificity of the compound for genotypes 1 and 3. Surprisingly, resistance mutations selected against 15d were mapped to domains II and III of the nonstructural protein 5A (NS5A), but not to the RNA-dependent RNA polymerase residing in NS5B...
February 28, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28240747/antibodies-against-nonstructural-protein-1-protect-mice-from-dengue-virus-induced-mast-cell-activation
#15
Ya-Ting Chu, Shu-Wen Wan, Yu-Chang Chang, Chien-Kuo Lee, Betty A Wu-Hsieh, Robert Anderson, Yee-Shin Lin
Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). DHF/DSS patients have been reported to have increased levels of urinary histamine, chymase, and tryptase, which are major granule-associated mediators from mast cells. Previous studies also showed that DENV-infected human mast cells induce production of proinflammatory cytokines and chemokines, suggesting a role played by mast cells in vascular perturbation as well as leukocyte recruitment. In this study, we show that DENV but not UV-inactivated DENV enhanced degranulation of mast cells and production of chemokines (MCP-1, RANTES, and IP-10) in a mouse model...
February 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28236746/discovery-of-a-novel-antiviral-agent-targeting-the-nonstructural-protein-4-nsp4-of-chikungunya-virus
#16
Yuji Wada, Yasuko Orba, Michihito Sasaki, Shintaro Kobayashi, Michael J Carr, Haruaki Nobori, Akihiko Sato, William W Hall, Hirofumi Sawa
Chikungunya fever (CHIKF) is caused by chikungunya virus (CHIKV) infection which is a re-emerging mosquito-borne zoonosis. At present, there are no approved therapeutics for CHIKF. Herein, we have investigated candidate compounds which can inhibit CHIKV infection. Screening of chemical compound libraries were performed and one candidate, a benzimidazole-related compound designated Compound-A was found to inhibit infection by several CHIKV strains and a Sindbis virus strain at nanomolar concentrations. To investigate the inhibitory mechanism of action, a Compound-A resistant CHIKV (res-CHIKV) was isolated and a key mutation associated with resistance was identified by reverse-genetic recombinant CHIKVs containing amino acid substitutions present in res-CHIKV...
February 22, 2017: Virology
https://www.readbyqxmd.com/read/28236252/clinical-pharmacokinetics-of-paritaprevir
#17
REVIEW
Rajeev M Menon, Akshanth R Polepally, Amit Khatri, Walid M Awni, Sandeep Dutta
Paritaprevir is a potent hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor that is used in combination with other direct-acting antivirals (DAAs) for the treatment of chronic HCV infection. Paritaprevir is primarily metabolized by cytochrome P450 (CYP) 3A4 and is administered with a low dose of ritonavir to achieve drug concentrations suitable for once-daily dosing. Coadministration of paritaprevir with ritonavir increases the half-life of single-dose paritaprevir from approximately 3 h to 5-8 h, doubles the time to maximum plasma concentration (T max) from 2...
February 25, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28235682/nuclear-imprisonment-of-host-cellular-mrna-by-nsp1%C3%AE-protein-of-porcine-reproductive-and-respiratory-syndrome-virus
#18
Mingyuan Han, Hanzhong Ke, Qingzhan Zhang, Dongwan Yoo
Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome...
February 18, 2017: Virology
https://www.readbyqxmd.com/read/28229375/clinical-pharmacokinetics-of-ombitasvir
#19
REVIEW
Prajakta S Badri, Diana L Shuster, Sandeep Dutta, Rajeev M Menon
Ombitasvir is a potent, nonstructural protein 5A inhibitor of the hepatitis C virus (HCV) that is used in combination with other direct-acting antivirals for the treatment of chronic HCV infection. Ombitasvir is predominantly metabolized by amide hydrolysis followed by oxidative metabolism and is a substrate of P-glycoprotein. Ombitasvir displays linear pharmacokinetics with minimal accumulation and is eliminated via metabolism and biliary excretion. A negligible amount of unchanged drug is excreted in urine...
February 22, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28223026/development-and-application-of-nsp5-elisa-for-the-detection-of-antibody-to-infectious-bronchitis-virus
#20
Jing Lei, Tingting Shi, Dongnan Sun, Kaikun Mo, Yan Yan, Yulan Jin, Min Liao, Jiyong Zhou
Infectious bronchitis virus (IBV) continues to be one of the most important poultry pathogens worldwide. The current commercially available enzyme-linked immunosorbent assay (ELISA) kits for IBV specific antibody detection are mostly based on the whole virion, and few serological tests based on nonstructural proteins of IBV have been developed. Herein, an alternative indirect ELISA for detection of IBV antibody was developed with IBV nonstructural protein 5 (nsp5) produced by Escherichia coli. Using an indirect immunofluorescence assay (IFA) and a commercial ELISA kit as reference, we optimized the nsp5-ELISA and determined its cut-off as 0...
May 2017: Journal of Virological Methods
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