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https://www.readbyqxmd.com/read/27902334/the-ns1-protein-of-avian-influenza-virus-h9n2-induces-oxidative-stress-mediated-chicken-oviduct-epithelial-cells-coecs-apoptosis
#1
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/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
#2
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/27881649/the-many-faces-of-the-flavivirus-ns5-protein-in-antagonism-of-type-i-interferon-signaling
#3
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
#4
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/27870604/immunoreactivity-analysis-of-the-nonstructural-proteins-of-human-enterovirus-71
#5
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
#6
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/27844505/conformer-and-pharmacophore-based-identification-of-peptidomimetic-inhibitors-of-chikungunya-virus-nsp2-protease
#7
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/27803188/hepatitis-c-virus-proteins-interact-with-the-endosomal-sorting-complex-required-for-transport-escrt-machinery-via-ubiquitination-to-facilitate-viral-envelopment
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27769040/microrna-like-viral-small-rna-from-porcine-reproductive-and-respiratory-syndrome-virus-negatively-regulates-viral-replication-by-targeting-the-viral-nonstructural-protein-2
#12
Na Li, Yunhuan Yan, Angke Zhang, Jiming Gao, Chong Zhang, Xue Wang, Gaopeng Hou, Gaiping Zhang, Jinbu Jia, En-Min Zhou, Shuqi Xiao
Many viruses encode microRNAs (miRNAs) that are small non-coding single-stranded RNAs which play critical roles in virus-host interactions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically impactful viruses in the swine industry. The present study sought to determine whether PRRSV encodes miRNAs that could regulate PRRSV replication. Four viral small RNAs (vsRNAs) were mapped to the stem-loop structures in the ORF1a, ORF1b and GP2a regions of the PRRSV genome by bioinformatics prediction and experimental verification...
October 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27764162/novel-strategy-to-control-transgene-expression-mediated-by-a-sendai-virus-based-vector-using-a-nonstructural-c-protein-and-endogenous-micrornas
#13
Masayuki Sano, Minoru Iijima, Manami Ohtaka, Mahito Nakanishi
Tissue-specific control of gene expression is an invaluable tool for studying various biological processes and medical applications. Efficient regulatory systems have been utilized to control transgene expression in various types of DNA viral or integrating viral vectors. However, existing regulatory systems are difficult to transfer into negative-strand RNA virus vector platforms because of significant differences in their transcriptional machineries. In this study, we developed a novel strategy for regulating transgene expression mediated by a cytoplasmic RNA vector based on a replication-defective and persistent Sendai virus (SeVdp)...
2016: PloS One
https://www.readbyqxmd.com/read/27743750/molecular-evolution-of-human-coronavirus-genomes
#14
Diego Forni, Rachele Cagliani, Mario Clerici, Manuela Sironi
Human coronaviruses (HCoVs), including SARS-CoV and MERS-CoV, are zoonotic pathogens that originated in wild animals. HCoVs have large genomes that encode a fixed array of structural and nonstructural components, as well as a variety of accessory proteins that differ in number and sequence even among closely related CoVs. Thus, in addition to recombination and mutation, HCoV genomes evolve through gene gains and losses. In this review we summarize recent findings on the molecular evolution of HCoV genomes, with special attention to recombination and adaptive events that generated new viral species and contributed to host shifts and to HCoV emergence...
October 19, 2016: Trends in Microbiology
https://www.readbyqxmd.com/read/27738977/characteristics-and-functions-of-hev-proteins
#15
Yan Zhou, Chenyan Zhao, Yabin Tian, Nan Xu, Youchun Wang
Hepatitis E virus (HEV) is a non-enveloped virus containing a single-stranded, positive-sense RNA genome of 7.2 kb, which consists of a 5' noncoding region, three open reading frames (ORFs), and a 3' noncoding region. ORF1 is diverse between genotypes and encodes the nonstructural proteins, which include the enzymes needed for virus replication. In addition to its role in virus replication, the function of ORF1 is relevant to viral adaption in cultured cells and may also relate to virus infection and HEV pathogenicity...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27736706/identification-of-viral-genes-associated-with-the-interferon-inducing-phenotype-of-a-synthetic-porcine-reproductive-and-respiratory-syndrome-virus-strain
#16
Haiyan Sun, Asit K Pattnaik, Fernando A Osorio, Hiep L X Vu
We recently generated a fully synthetic porcine reproductive and respiratory syndrome virus strain (designated as PRRSV-CON), which confers unprecedented levels of heterologous protection. We report herein that the synthetic PRRSV-CON possesses a unique phenotype in that it induces type-I interferons (IFNs) instead of suppressing these cytokines as most of the naturally occurring PRRSV isolates do. Through gain- and loss- of-function studies, the IFN-inducing phenotype of PRRSV-CON was mapped to the 3.3kb genomic fragment encoding three viral nonstructural proteins: nsp1α, nsp1β and the N-terminal part of nsp2...
October 10, 2016: Virology
https://www.readbyqxmd.com/read/27729840/virtual-screening-for-potential-inhibitors-of-ns3-protein-of-zika-virus
#17
Maheswata Sahoo, Lingaraja Jena, Sangeeta Daf, Satish Kumar
Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family...
September 2016: Genomics & Informatics
https://www.readbyqxmd.com/read/27718266/the-influenza-a-virus-nonstructural-protein-ns1-up-regulates-the-expression-of-collagen-triple-helix-repeat-containing-1-protein
#18
Chengliang Zhu, Guiqing Peng, Wei Yi, Hui Song, Fang Liu, Xinghui Liu
Influenza A virus (IAV) infection induces a strong immune response and regulates the expression of many host proteins. The collagen triple helix repeat containing 1 (CTHRC1) protein is a secreted protein that exhibits increased expression during the viral infection process. However, the regulatory function of IAV on CTHRC1 expression is obscure. In this study, we investigated the effect of IAV on CTHRC1 expression and its regulatory mechanism. A total of 106 serum specimens from healthy people and 80 serum specimens from patients infected with IAV were collected...
October 8, 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27712628/the-nonstructural-proteins-directing-coronavirus-rna-synthesis-and-processing
#19
E J Snijder, E Decroly, J Ziebuhr
Coronaviruses are animal and human pathogens that can cause lethal zoonotic infections like SARS and MERS. They have polycistronic plus-stranded RNA genomes and belong to the order Nidovirales, a diverse group of viruses for which common ancestry was inferred from the common principles underlying their genome organization and expression, and from the conservation of an array of core replicase domains, including key RNA-synthesizing enzymes. Coronavirus genomes (~26-32 kilobases) are the largest RNA genomes known to date and their expansion was likely enabled by acquiring enzyme functions that counter the commonly high error frequency of viral RNA polymerases...
2016: Advances in Virus Research
https://www.readbyqxmd.com/read/27712623/viral-and-cellular-mrna-translation-in-coronavirus-infected-cells
#20
K Nakagawa, K G Lokugamage, S Makino
Coronaviruses have large positive-strand RNA genomes that are 5' capped and 3' polyadenylated. The 5'-terminal two-thirds of the genome contain two open reading frames (ORFs), 1a and 1b, that together make up the viral replicase gene and encode two large polyproteins that are processed by viral proteases into 15-16 nonstructural proteins, most of them being involved in viral RNA synthesis. ORFs located in the 3'-terminal one-third of the genome encode structural and accessory proteins and are expressed from a set of 5' leader-containing subgenomic mRNAs that are synthesized by a process called discontinuous transcription...
2016: Advances in Virus Research
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