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https://www.readbyqxmd.com/read/28545480/effects-of-hepatitis-c-virus-core-protein-and-nonstructural-protein-4b-on-the-wnt-%C3%AE-catenin-pathway
#1
Xiao-Hua Jiang, Yu-Tao Xie, Ya-Ping Cai, Jing Ren, Tao Ma
BACKGROUND: Hepatitis C virus (HCV) core protein and nonstructural protein 4B (NS4B) are potentially oncogenic. Aberrant activation of the Wnt/β-catenin signaling pathway is closely associated with hepatocarcinogenesis. We investigated the effects of HCV type 1b core protein and NS4B on Wnt/β-catenin signaling in various liver cells, and explored the molecular mechanism underlying HCV-related hepatocarcinogenesis. RESULTS: Compared with the empty vector control, HCV core protein and NS4B demonstrated the following characteristics in the Huh7 cells: significantly enhanced β-catenin/Tcf-dependent transcriptional activity (F = 40...
May 25, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28539454/ebola-virus-delta-peptide-is-a-viroporin
#2
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/28535337/overall-structural-model-of-ns5a-protein-from-hepatitis-c-virus-and-modulation-by-mutations-confering-resistance-of-virus-replication-to-cyclosporin-a
#3
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/28529975/phylogenetic-analyses-suggest-that-factors-other-than-the-capsid-protein-play-a-role-in-the-epidemic-potential-of-gii-2-norovirus
#4
Kentaro Tohma, Cara J Lepore, Lauren A Ford-Siltz, Gabriel I Parra
Norovirus is the leading cause of acute gastroenteritis worldwide. For over two decades, a single genotype (GII.4) has been responsible for most norovirus-associated cases. However, during the winter of 2014 to 2015, the GII.4 strains were displaced by a rarely detected genotype (GII.17) in several countries of the Asian continent. Moreover, during the winter of 2016 to 2017, the GII.2 strain reemerged as predominant in different countries worldwide. This reemerging GII.2 strain is a recombinant virus that presents a GII...
May 2017: MSphere
https://www.readbyqxmd.com/read/28527257/-polyclonal-antibodies-against-recombinant-dengue-virus-ns3-protein
#5
Liliana Morales, Myriam L Velandia, María Angélica Calderon, Jaime E Castellanos, Jacqueline Chaparro-Olaya
INTRODUCTION: Dengue is a disease caused by one of four serotypes of the dengue virus (DENV) and is endemic in approximately 130 countries. The incidence of dengue has increased dramatically in recent decades, as well as the frequency and magnitude of outbreaks. Despite all efforts, there are no prophylactic or therapeutic treatments for the disease. Accordingly, research on the processes governing the DENV infection cycle is essential to develop vaccines or antiviral therapies. One of themost attractive DENV molecules to investigate is nonstructural protein 3 (NS3), which is essential for viral replication and a major immune target for infection...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28518476/adult-onset-chronic-cyclic-thrombocytopenia-in-a-rhesus-macaque-macaca-mulatta-after-dengue-virus-vaccination-and-viral-challenge
#6
Galit H Frydman, Kelly A Metcalf Pate, Robert P Marini, Armelle M de Laforcade, Irene Bosch, Vasudevan Bakthavatchalu, Sureshkumar Muthupalani, Alton G Swennes, Claire E Lyons, Ronald G Tompkins, James G Fox
An 8-year-old, male Rhesus macaque (Macaca mulatta), previously used for dengue virus (DENV) vaccine research with viral challenge, was presented with adult-onset, chronic, cyclic thrombocytopenia. Platelet number, morphology, and function were evaluated by automated hematology, peripheral blood smears, electron microscopy, flow cytometry, and impedance aggregometry. Bone marrow was evaluated by cytology. Both serum anti-dengue nonstructural protein 1 (NS1) antibodies and anti-platelet antibodies were detected by ELISA...
May 18, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28514196/interactions-between-ns1-of-influenza-a-viruses-and-interferon-%C3%AE-%C3%AE-determinants-for-vaccine-development
#7
Ben X Wang, Eleanor N Fish
Influenza A viruses (IAVs) cause mild to severe infections in humans with considerable socioeconomic and global health consequences. The host interferon (IFN)-α/β response, critical as the first line of defense against foreign pathogens, is induced upon detection of IAV genomic RNA in infected cells by host innate pattern recognition receptors. IFN-α/β production and subsequent activation of cell signaling result in the expression of antiviral IFN-stimulated genes whose products target various stages of the IAV life cycle to inhibit viral replication and the spread of infection and establish an antiviral state...
May 17, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28508043/crystal-structure-of-2c-helicase-from-enterovirus-71
#8
Hongxin Guan, Juan Tian, Bo Qin, Justyna Aleksandra Wojdyla, Bei Wang, Zhendong Zhao, Meitian Wang, Sheng Cui
Enterovirus 71 (EV71) is the major pathogen responsible for outbreaks of hand, foot, and mouth disease. EV71 nonstructural protein 2C participates in many critical events throughout the virus life cycle; however, its precise role is not fully understood. Lack of a high-resolution structure made it difficult to elucidate 2C activity and prevented inhibitor development. We report the 2.5 Å-resolution crystal structure of the soluble part of EV71 2C, containing an adenosine triphosphatase (ATPase) domain, a cysteine-rich zinc finger with an unusual fold, and a carboxyl-terminal helical domain...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28501618/assessing-activity-of-hepatitis-a-virus-3c-protease-using-a-cyclized-luciferase-based-biosensor
#9
Junwei Zhou, Dang Wang, Yongqiang Xi, Xinyu Zhu, Yuting Yang, Mengting Lv, Chuanzhen Luo, Jiyao Chen, Xu Ye, Liurong Fang, Shaobo Xiao
Hepatitis A is an acute infection caused by Hepatitis A virus (HAV), which is widely distributed throughout the world. The HAV 3C cysteine protease (3C(pro)), an important nonstructural protein, is responsible for most cleavage within the viral polyprotein and is critical for the processes of viral replication. Our group has previously demonstrated that HAV 3C(pro) cleaves human NF-κB essential modulator (NEMO), a kinase required in interferon signaling. Based on this finding, we generated four luciferase-based biosensors containing the NEMO sequence (PVLKAQ↓ADIYKA) that is cleaved by HAV 3C(pro) and/or the Nostoc punctiforme DnaE intein, to monitor the activity of HAV 3C(pro) in human embryonic kidney cells (HEK-293T)...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28500445/genetic-diversity-and-evolutionary-characteristics-of-type-2-porcine-reproductive-and-respiratory-syndrome-virus-in-southeastern-china-from-2009-to-2014
#10
Jiankui Liu, Xia Zhou, Junqiong Zhai, Bing Li, Chunhua Wei, Ailing Dai, Xiaoyan Yang, Manlin Luo
The objective of this study was to assess the genetic diversity of porcine reproductive and respiratory syndrome virus circulating in Fujian province (southeastern China). Based on 53 ORF5 nucleotide sequences collected from nine sites, both highly pathogenic (sublineage 8.7) and lineage 1 strains were circulating in Fujian in 2009-2014 along with lineages 3 and 5.1. Notably, the lineage 1 strains were closely related to the NADC30 strain circulating in North America and were the predominant strains in 2014...
May 12, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28493152/inhibition-of-mir-274-3p-increases-bmcpv-replication-by-regulating-the-expression-of-bmcpv-ns5-gene-in-bombyx-mori
#11
Ping Wu, Xiaoxu Jiang, Qi Sang, Enoch Annan, Tao Cheng, Xijie Guo
Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) is one of the major pathogens that pose a big challenge to the sericulture industry. Growing evidences have shown that microRNAs play key roles in the regulations of host-pathogen interactions in insects. MicroRNAs have been found in silkworms, whether and how they affect the silkworm-BmCPV interactions are still unknown. Here we investigate the effect of miR-274-3p on the BmCPV replication in the BmCPV-infected silkworm larvae. In our study, BmCPV Nonstructural protein 5 (NS5) was identified to be the target of miR-274-3p based on bioinformatics analysis and luciferase reporter assay...
May 10, 2017: Virus Genes
https://www.readbyqxmd.com/read/28490497/protein-composition-of-the-hepatitis-a-virus-quasi-envelope
#12
Kevin L McKnight, Ling Xie, Olga González-López, Efraín E Rivera-Serrano, Xian Chen, Stanley M Lemon
The Picornaviridae are a diverse family of RNA viruses including many pathogens of medical and veterinary importance. Classically considered "nonenveloped," recent studies show that some picornaviruses, notably hepatitis A virus (HAV; genus Hepatovirus) and some members of the Enterovirus genus, are released from cells nonlytically in membranous vesicles. To better understand the biogenesis of quasi-enveloped HAV (eHAV) virions, we conducted a quantitative proteomics analysis of eHAV purified from cell-culture supernatant fluids by isopycnic ultracentrifugation...
May 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28484023/coronavirus-nonstructural-protein-15-mediates-evasion-of-dsrna-sensors-and-limits-apoptosis-in-macrophages
#13
Xufang Deng, Matthew Hackbart, Robert C Mettelman, Amornrat O'Brien, Anna M Mielech, Guanghui Yi, C Cheng Kao, Susan C Baker
Coronaviruses are positive-sense RNA viruses that generate double-stranded RNA (dsRNA) intermediates during replication, yet evade detection by host innate immune sensors. Here we report that coronavirus nonstructural protein 15 (nsp15), an endoribonuclease, is required for evasion of dsRNA sensors. We evaluated two independent nsp15 mutant mouse coronaviruses, designated N15m1 and N15m3, and found that these viruses replicated poorly and induced rapid cell death in mouse bone marrow-derived macrophages. Infection of macrophages with N15m1, which expresses an unstable nsp15, or N15m3, which expresses a catalysis-deficient nsp15, activated MDA5, PKR, and the OAS/RNase L system, resulting in an early, robust induction of type I IFN, PKR-mediated apoptosis, and RNA degradation...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28471365/structural-features-of-ns3-of-dengue-virus-serotypes-2-and-4-in-solution-and-insight-into-rna-binding-and-the-inhibitory-role-of-quercetin
#14
Ankita Pan, Wuan Geok Saw, Malathy Sony Subramanian Manimekalai, Ardina Grüber, Shin Joon, Tsutomu Matsui, Thomas M Weiss, Gerhard Grüber
Dengue virus (DENV), which has four serotypes (DENV-1 to DENV-4), is the causative agent of the viral infection dengue. DENV nonstructural protein 3 (NS3) comprises a serine protease domain and an RNA helicase domain which has nucleotide triphosphatase activities that are essential for RNA replication and viral assembly. Here, solution X-ray scattering was used to provide insight into the overall structure and flexibility of the entire NS3 and its recombinant helicase and protease domains for Dengue virus serotypes 2 and 4 in solution...
May 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28469422/seroprevalence-of-asymptomatic-dengue-virus-infection-and-its-antibodies-among-healthy-eligible-saudi-blood-donors-findings-from-holy-makkah-city
#15
Ahmed M Ashshi, Saad Alghamdi, Adel G El-Shemi, Sabir Almdani, Bassem Refaat, Amr M Mohamed, Hani O Ghazi, Esam I Azhar, Faisal A Al-Allaf
BACKGROUND: Threat to blood transfusion-transmitted dengue virus (DENV) and its antibodies has recently emerged worldwide. Dengue fever is an endemic disease in Saudi Arabia, particularly in its Western region. The aim of this study was to estimate the seroprevalence of asymptomatic DENV infection and its antibodies among eligible Saudi blood donors. METHODS: Serum samples from 910 healthy/eligible adult male Saudi blood donors, who reside in Holy Makkah City of Saudi Arabia, were collected between March 2015 and August 2016 and screened for the detection of DENV nonstructural protein 1 (NS1) antigen and anti-DENV IgM and IgG antibodies using commercial enzyme-linked immunosorbent assay kits (Panbio, Brisbane, QLD, Australia)...
2017: Virology: Research and Treatment
https://www.readbyqxmd.com/read/28469408/modification-of-s-adenosyl-l-homocysteine-as-inhibitor-of-nonstructural-protein-5-methyltransferase-dengue-virus-through-molecular-docking-and-molecular-dynamics-simulation
#16
Usman Sumo Friend Tambunan, Mochammad Arfin Fardiansyah Nasution, Fauziah Azhima, Arli Aditya Parikesit, Erwin Prasetya Toepak, Syarifuddin Idrus, Djati Kerami
Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world's population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2'OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test...
2017: Drug Target Insights
https://www.readbyqxmd.com/read/28466041/indian-porcine-reproductive-and-respiratory-syndrome-virus-bears-discontinuous-deletion-of-30-amino-acids-in-nonstructural-protein-2
#17
T K Rajkhowa, G Jagan Mohanarao, A Gogoi, L Hauhnar
Since its first outbreak in 2013, porcine reproductive and respiratory syndrome (PRRS) has established as an enzootic disease in pig population of Mizoram state, India. Our previous studies based on phylogenetic analysis of ORF5 and ORF7 gene sequences revealed close relationship of Indian PRRSV with the highly pathogenic variant of PRRSV (HP-PRRSV) of Chinese origin. Despite the control measures, second major outbreak of the disease was recorded in Aizawl district of Mizoram in 2015. The objective of the present study was to examine the origin of PRRSV isolates of 2015 outbreak, identification of deleted region in Nsp2 gene and determination of any genetic variation between 2013 and 2015 isolates of PRRSV...
September 2016: Virusdisease
https://www.readbyqxmd.com/read/28446677/variable-inhibition-of-zika-virus-replication-by-different-wolbachia-strains-in-mosquito-cell-cultures
#18
Michaela J Schultz, Sharon Isern, Scott F Michael, Ronald B Corley, John Connor, Horacio M Frydman
Mosquito-borne arboviruses are a major source of human disease. One strategy to reduce arbovirus disease is to reduce the mosquito's ability to transmit virus. Mosquito infection with bacterial endosymbiont, Wolbachia pipientis wMel, is a novel strategy to reduce Aedes mosquito competency for flavivirus infection. However, experiments investigating cyclic environmental temperatures have shown a reduction in maternal transmission of wMel potentially weakening the integration of this strain into a mosquito population relative to other Wolbachia strains...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446674/broadening-cd4-and-cd8-t-cell-responses-against-hepatitis-c-virus-by-vaccination-with-ns3-overlapping-peptide-panels-in-cross-priming-liposomes
#19
Jonathan Filskov, Marianne Mikkelsen, Paul R Hansen, Jan P Christensen, Allan R Thomsen, Peter Andersen, Jens Bukh, Else Marie Agger
Despite the introduction of effective drugs to treat patients with chronic hepatitis C virus (HCV) infection, a vaccine would be the only means to substantially reduce the worldwide disease burden. An incomplete understanding of how HCV interacts with its human host and evades immune surveillance has hampered vaccine development. It is generally accepted that in infected individuals, a narrow repertoire of exhausted T cells is a hallmark of persistent infection, whereas broad vigorous CD4(+) and CD8(+) T cell responses are associated with control of acute hepatitis C...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28417013/erratum-zika-virus-evades-interferon-mediated-antiviral-response-through-the-co-operation-of-multiple-nonstructural-proteins-in-vitro
#20
Yaoxing Wu, Qingxiang Liu, Jie Zhou, Weihong Xie, Cheng Chen, Zefang Wang, Haitao Yang, Jun Cui
[This corrects the article DOI: 10.1038/celldisc.2017.6.].
2017: Cell Discovery
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