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https://www.readbyqxmd.com/read/27905537/unique-nonstructural-proteins-of-pneumonia-virus-of-mice-pvm-promote-degradation-of-interferon-ifn-pathway-components-and-ifn-stimulated-gene-proteins
#1
Jayeeta Dhar, Sailen Barik
Pneumonia Virus of Mice (PVM) is the only virus that shares the Pneumovirus genus of the Paramyxoviridae family with Respiratory Syncytial Virus (RSV). A deadly mouse pathogen, PVM has the potential to serve as a robust animal model of RSV infection, since human RSV does not fully replicate the human pathology in mice. Like RSV, PVM also encodes two nonstructural proteins that have been implicated to suppress the IFN pathway, but surprisingly, they exhibit no sequence similarity with their RSV equivalents. The molecular mechanism of PVM NS function, therefore, remains unknown...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27902334/the-ns1-protein-of-avian-influenza-virus-h9n2-induces-oxidative-stress-mediated-chicken-oviduct-epithelial-cells-coecs-apoptosis
#2
Xuefeng Qi, Huizhu Zhang, Qiuzhen Wang, Jingyu Wang
The pathogenesis of H9N2 subtype avian influenza virus infection (AIV) in the hens is often related to the oviduct tissue damage. The viral nonstructural NS1 protein is thought to play key role in regulating the pathogenicity of AIV, but the exact function to this process remains elusive. In this study, the pro-apoptosis effect of H9N2 NS1 protein was examined on chicken oviduct epithelial cells (COECs) and our data suggested that NS1 induced oxidative stress was a contributing factor for apoptosis. Our data suggest that NS1 protein level was correlated with reactive oxygen species (ROS) in COECs cells transfected with NS1 expression plasmids...
October 20, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27898592/the-hepatitis-c-virus-nonstructural-protein-3-q80k-polymorphism-is-frequently-detected-and-transmitted-among-hiv-infected-msm-in-the-netherlands
#3
Astrid M Newsum, Cynthia K Y Ho, Faydra I Lieveld, Thijs J W van de Laar, Sylvie M Koekkoek, Sjoerd P Rebers, Jan T M van der Meer, Anne M J Wensing, Greet J Boland, Joop E Arends, Karel J van Erpecum, Maria Prins, Richard Molenkamp, Janke Schinkel
OBJECTIVES: The Q80K polymorphism is a naturally occurring resistance-associated variant in the hepatitis C virus (HCV) nonstructural protein 3 (NS3) region and is likely transmissible between hosts. This study describes the Q80K origin and prevalence among HCV risk groups in the Netherlands and examines whether Q80K is linked to specific transmission networks. DESIGN AND METHODS: Stored blood samples from HCV genotype 1a-infected patients were used for PCR and sequencing to reconstruct the NS3 maximum likelihood phylogeny...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27886347/genetic-variability-of-myzus-persicae-nicotianae-densovirus-based-on-partial-ns-and-vp-gene-sequences
#4
X R Song, S H Tang, Z Q Tang, X M Yang, X W Wang, X F Wang, P J Xu, G W Ren
We previously described a novel densovirus [Myzus persicae nicotianae densovirus (MpnDV)] infecting M. persicae nicotianae (Hemiptera: Aphididae) with 34% prevalence. This single-stranded DNA virus has a 5480-nucleotide ambisense genome and belongs to the Densovirinae subfamily within the family Parvoviridae. In the present study, we estimated the genetic diversity of MpnDV using partial nonstructural protein (NS) and capsid protein (VP) gene sequences from 10 locations in China. First, we identified MpnDV-positive samples by amplifying a 445-bp fragment with primers MpDVF/MpDVR...
November 21, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27881655/porcine-reproductive-and-respiratory-syndrome-virus-nsp1%C3%AE-inhibits-nf-%C3%AE%C2%BAb-activation-by-targeting-linear-ubiquitin-chain-assembly-complex-lubac
#5
Huiyuan Jing, Liurong Fang, Zhen Ding, Dang Wang, Wenqi Hao, Li Gao, Wenting Ke, Huanchun Chen, Shaobo Xiao
: Linear ubiquitination, a newly discovered posttranslational modification, is catalyzed by the linear ubiquitin chain assembly complex (LUBAC), which is composed of three subunits: one catalytic subunit HOIP and two accessory molecules, HOIL-1L and SHARPIN. Accumulating evidence suggests that linear ubiquitination plays a crucial role in innate immune signaling and especially in the activation of the NF-κB pathway by conjugating linear polyubiquitin chains to NF-κB essential modulator (NEMO, also called IKKγ), the regulatory subunit of the IKK complex...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27881651/alternative-polyadenylation-of-human-bocavirus-at-its-3-end-is-regulated-by-multiple-elements-and-affects-capsid-expression
#6
Sujuan Hao, Junmei Zhang, Zhen Chen, Huanzhou Xu, Hanzhong Wang, Wuxiang Guan
: Alternative processing of human bocavirus (HBoV) P5 promoter-transcribed RNA is critical for generating the structural and nonstructural protein-encoding mRNA transcripts. The regulatory mechanism by which HBoV RNA transcripts are polyadenylated at proximal [(pA)p] or distal [(pA)d] polyadenylation sites is yet unclear. We constructed a recombinant HBoV infectious clone to study the alternative polyadenylation regulation of HBoV. Surprisingly, in addition to the reported distal polyadenylation site (pA)d, a novel distal polyadenylation site (pA)d2 which is located in the right end hairpin (REH), was identified during infectious clone transfection or recombinant virus infection...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27881649/the-many-faces-of-the-flavivirus-ns5-protein-in-antagonism-of-type-i-interferon-signaling
#7
Sonja M Best
The vector-borne flaviviruses cause severe disease in humans on every inhabited continent on earth. Their transmission by arthropods, particularly mosquitoes, facilitates large emergence events such as witnessed with Zika virus (ZIKV) or West Nile virus in the Americas. Every vector-borne flavivirus examined thus far that causes disease in humans, from dengue virus to ZIKV, antagonizes the host type I interferon (IFN-I) response by preventing JAK-STAT signaling, suggesting that suppression of this pathway is an important determinant of infection...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27876044/generation-of-monoclonal-antibodies-against-native-viral-proteins-using-antigen-expressing-mammalian-cells-for-mouse-immunization
#8
Natalie Rose, Carlos Augusto Pinho-Nascimento, Alessia Ruggieri, Paola Favuzza, Marco Tamborrini, Hanna Roth, Marcia Terezinha Baroni de Moraes, Hugues Matile, Thomas Jänisch, Gerd Pluschke, Katharina Röltgen
BACKGROUND: Due to their rising incidence and progressive geographical spread, infections with mosquito-borne viruses, such as dengue (DENV), chikungunya and zika virus, have developed into major public health challenges. Since all of these viruses may cause similar symptoms and can occur in concurrent epidemics, tools for their differential diagnosis and epidemiological monitoring are of urgent need. RESULTS: Here we report the application of a novel strategy to rapidly generate monoclonal antibodies (mAbs) against native viral antigens, exemplified for the DENV nonstructural glycoprotein 1 (NS1)...
November 22, 2016: BMC Biotechnology
https://www.readbyqxmd.com/read/27875810/nonstructural-protein-1-of-tick-borne-encephalitis-virus-induces-oxidative-stress-and-activates-antioxidant-defense-by-the-nrf2-are-pathway
#9
Yulia V Kuzmenko, Olga A Smirnova, Alexander V Ivanov, Elizaveta S Starodubova, Vadim L Karpov
BACKGROUND: Infection with tick-borne encephalitis virus (TBEV) causes pathological changes in the central nervous system. However, the possible redox alterations in the infected cells that can contribute to the virus pathogenicity remain unknown. OBJECTIVE: In the current study we explored the ability of TBEV nonstructural protein 1 (NS1) to induce oxidative stress and activate antioxidant defense via the nuclear factor (erythroid-derived-2)-like 2/antioxidant response element (Nrf2/ARE) pathway...
November 23, 2016: Intervirology
https://www.readbyqxmd.com/read/27870604/immunoreactivity-analysis-of-the-nonstructural-proteins-of-human-enterovirus-71
#10
Xuyan Chen, Bo Qin, Min Shi, Longying Zhu, Menglin Sun, Xufeng Liu, Jianhua Zhang
Human enterovirus 71 (EV-A71) is one of the main etiological agents of hand, foot, and mouth disease (HFMD), which has been prevalent mainly in the Asia-Pacific region in the past several decades. The nonstructural proteins of EV-A71 will be expressed significantly during viral replication in host cells after EV-A71 infection. For the determination of the antibodies response against nonstructural proteins of EV-A71, in this study, the complete 2ABC, 3ABC, and 3D proteins were expressed in Escherichia coli and were then studied for their immunoreactivity by immunoblot assay and indirect enzyme-linked immunosorbent assay (ELISA), respectively...
November 21, 2016: Viral Immunology
https://www.readbyqxmd.com/read/27866982/structure-of-the-ns5-methyltransferase-from-zika-virus-and-implications-in-inhibitor-design
#11
Caiying Zhang, Tingting Feng, Jinbo Cheng, Yajuan Li, Xueying Yin, Weihong Zeng, Xiangyu Jin, Yuelong Li, Feng Guo, Tengchuan Jin
Recent outbreak of flavivirus Zika virus (ZIKV) in America has urged the basic as well as translational studies of this important human pathogen. The nonstructural protein 5 (NS5) of the flavivirus has an N-terminal methyltransferase (MTase) domain that plays critical roles in viral RNA genome capping. The null mutant of NS5 MTase is lethal for virus. Therefore, NS5 is a potential drug target for the treatment of Zika virus infection. In this study, we determined crystal structures of the ZIKV MTase in complex with GTP and RNA cap analogue (7me)GpppA...
November 17, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27863806/pharmacokinetics-safety-and-tolerability-of-single-and-multiple-doses-of-abt-493-a-first-in-human-study
#12
Chih-Wei Lin, Sandeep Dutta, Armen Asatryan, Yi-Lin Chiu, Haoyu Wang, Jack Clifton, Andrew Campbell, Wei Liu
ABT-493 is a hepatitis C virus nonstructural protein 3/4A protease inhibitor with pangenotypic antiviral activity. This study investigated the pharmacokinetics, safety, and tolerability of single and multiple ascending doses of ABT-493 and the effect of food and ritonavir coadministration on ABT-493 pharmacokinetics in healthy adults. In the blinded, randomized, placebo-controlled phase 1 single- and multiple-dose portions of the study, ABT-493 25-800 mg were evaluated as single doses, and 200, 400, and 800 mg were evaluated as multiple doses...
November 15, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27858288/complete-genomic-characterization-of-two-european-genotype-porcine-reproductive-and-respiratory-syndrome-virus-isolates-in-fujian-province-of-china
#13
Jian-Kui Liu, Chun-Hua Wei, Ai-Ling Dai, Ke-Wei Fan, Bing-Hui Yang, Chun-Fang Huang, Xiao-Hua Li, Xiao-Yan Yang, Man-Lin Luo
Porcine reproductive and respiratory syndrome (PRRS) is considered one of the most devastating swine diseases worldwide, resulting in immense economic losses. PRRS virus (PRRSV) is divided into two major genotypes, European (type 1) and the North American (type 2). Type 1 PRRSV have recently emerged in Fujian province (South China), and this might have a significant impact on the Chinese pig industry. From 2013 to 2014, two type 1 PRRSV strains, named FJEU13 and FJQEU14, were isolated from piglets and sows with respiratory problems and reproductive disorders in Fujian province...
November 17, 2016: Archives of Virology
https://www.readbyqxmd.com/read/27844505/conformer-and-pharmacophore-based-identification-of-peptidomimetic-inhibitors-of-chikungunya-virus-nsp2-protease
#14
Sonali Dhindwal, Pooja Kesari, Harvijay Singh, Pravindra Kumar, Shailly Tomar
Chikungunya virus nsP2 replication protein is a cysteine protease, which cleaves the nonstructural nsP1234 polyprotein into functional replication components. The cleavage and processing of nsP1234 by nsP2 protease is essential for the replication and proliferation of the virus. Thus, ChikV nsP2 protease is a promising target for antiviral drug discovery. In this study, the crystal structure of the C-terminal domain of ChikV nsP2 protease (PDB ID: 4ZTB) was used for structure based identification and rational designing of peptidomimetic inhibitors against nsP2 protease...
December 2, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27821666/duck-tembusu-virus-nonstructural-protein-1-antagonizes-ifn-%C3%AE-signaling-pathways-by-targeting-visa
#15
Junyong Wang, Cao-Qi Lei, Yanhong Ji, Hongbo Zhou, Yujie Ren, Qianqian Peng, Yan Zeng, Yane Jia, Jinying Ge, Bo Zhong, Yu Li, Jianzhong Wei, Hong-Bing Shu, Qiyun Zhu
Duck Tembusu virus (DTMUV) is an emergent infectious pathogen that has caused severe disease in ducks and huge economic losses to the poultry industry in China since 2009. Previously, we showed that DTMUV inhibits IFN-β induction early in infection; however, the mechanisms of the inhibition of innate immune responses remain poorly understood. In this study, we screened DTMUV-encoded structural and nonstructural proteins using reporter assays and found that DTMUV NS1 markedly suppressed virus-triggered IFN-β expression by inhibiting retinoic acid-inducible gene I-like receptor signaling...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27821177/hepatitis-b-virus-x-protein-promotes-interleukin-7-receptor-expression-via-nf-%C3%AE%C2%BAb-and-notch1-pathway-to-facilitate-proliferation-and-migration-of-hepatitis-b-virus-related-hepatoma-cells
#16
Fanyun Kong, Wei Hu, Kai Zhou, Xiao Wei, Yanbo Kou, Hongjuan You, Kuiyang Zheng, Renxian Tang
BACKGROUND: Interleukin-7 receptor (IL-7R) is involved in the abnormal function of solid tumors, but the role and regulatory mechanisms of IL-7R in HBV-related hepatocellular carcinoma (HCC) are still unclear. METHODS: Gene and protein expression levels of IL-7R were examined in hepatoma cells transfected with hepatitis B virus (HBV) plasmids and in hepatoma cells transfected with the multifunctional nonstructural protein X (HBX). The expression of HBX and IL-7R was measured by immunohistochemical analysis in HBV-related HCC tissues...
November 7, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27803188/hepatitis-c-virus-proteins-interact-with-the-endosomal-sorting-complex-required-for-transport-escrt-machinery-via-ubiquitination-to-facilitate-viral-envelopment
#17
Rina Barouch-Bentov, Gregory Neveu, Fei Xiao, Melanie Beer, Elena Bekerman, Stanford Schor, Joseph Campbell, Jim Boonyaratanakornkit, Brett Lindenbach, Albert Lu, Yves Jacob, Shirit Einav
: Enveloped viruses commonly utilize late-domain motifs, sometimes cooperatively with ubiquitin, to hijack the endosomal sorting complex required for transport (ESCRT) machinery for budding at the plasma membrane. However, the mechanisms underlying budding of viruses lacking defined late-domain motifs and budding into intracellular compartments are poorly characterized. Here, we map a network of hepatitis C virus (HCV) protein interactions with the ESCRT machinery using a mammalian-cell-based protein interaction screen and reveal nine novel interactions...
November 1, 2016: MBio
https://www.readbyqxmd.com/read/27798151/secreted-ns1-protects-dengue-virus-from-mannose-binding-lectin-mediated-neutralization
#18
Somchai Thiemmeca, Chamaiporn Tamdet, Nuntaya Punyadee, Tanapan Prommool, Adisak Songjaeng, Sansanee Noisakran, Chunya Puttikhunt, John P Atkinson, Michael S Diamond, Alongkot Ponlawat, Panisadee Avirutnan
Flavivirus nonstructural protein 1 (NS1) is a unique secreted nonstructural glycoprotein. Although it is absent from the flavivirus virion, intracellular and extracellular forms of NS1 have essential roles in viral replication and the pathogenesis of infection. The fate of NS1 in insect cells has been more controversial, with some reports suggesting it is exclusively cell associated. In this study, we confirm NS1 secretion from cells of insect origin and characterize its physical, biochemical, and functional properties in the context of dengue virus (DENV) infection...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27795408/the-nonstructural-protein-nss-of-schmallenberg-virus-is-targeted-to-the-nucleolus-and-induces-nucleolar-disorganization
#19
Julie Gouzil, Aurore Fablet, Estelle Lara, Grégory Caignard, Marielle Cochet, Cindy Kundlacz, Massimo Palmarini, Mariana Varela, Emmanuel Breard, Corinne Sailleau, Cyril Viarouge, Muriel Coulpier, Stéphan Zientara, Damien Vitour
: Schmallenberg virus (SBV) was discovered in Germany in late 2011 and then spread rapidly to many European countries. SBV is an orthobunyavirus that causes abortion and congenital abnormalities in ruminants. A virus-encoded non-structural protein, termed NSs, is a major virulence factor of SBV and it is known to promote the degradation of Rpb1, a subunit of the RNA Pol II complex, and therefore hampers global cellular transcription. In this study we found that NSs is mainly localized in the nucleus of infected cells, and, specifically appears to target the nucleolus through a nucleolar localization signal (NoLS) localized between residues 33 and 51 of the protein...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27784988/looking-for-inhibitors-of-the-dengue-virus-ns5-rna-dependent-rna-polymerase-using-a-molecular-docking-approach
#20
Vicente Galiano, Pablo Garcia-Valtanen, Vicente Micol, José Antonio Encinar
The dengue virus (DENV) nonstructural protein 5 (NS5) contains both an N-terminal methyltransferase domain and a C-terminal RNA-dependent RNA polymerase domain. Polymerase activity is responsible for viral RNA synthesis by a de novo initiation mechanism and represents an attractive target for antiviral therapy. The incidence of DENV has grown rapidly and it is now estimated that half of the human population is at risk of becoming infected with this virus. Despite this, there are no effective drugs to treat DENV infections...
2016: Drug Design, Development and Therapy
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