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https://www.readbyqxmd.com/read/28087593/norovirus-mediated-modification-of-the-translational-landscape-via-virus-and-host-induced-cleavage-of-translation-initiation-factors
#1
Edward Emmott, Frederic Sorgeloos, Sarah L Caddy, Surender Vashist, Stanislav Sosnovtsev, Richard Lloyd, Kate Heesom, Nicolas Locker, Ian Goodfellow
Noroviruses produce viral RNAs lacking a 5' cap structure and instead use a virus-encoded VPg protein covalently linked to viral RNA to interact with translation initiation factors and drive viral protein synthesis. Norovirus infection results in the induction of the innate response leading to interferon stimulated gene (ISG) transcription. However the translation of the induced ISG mRNAs is suppressed. A SILAC-based mass spectrometry approach was employed to analyse changes to protein abundance in both whole cell and m7GTP-enriched samples to demonstrate that diminished host mRNA translation correlates with changes to the composition of the eukaryotic initiation factor complex...
January 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28087495/comparative-analysis-of-variation-and-selection-in-the-hcv-genome
#2
Juan Ángel Patiño-Galindo, Fernando González-Candelas
Genotype 1 of the hepatitis C virus (HCV) is the most prevalent of the variants of this virus. Its two main subtypes, HCV-1a and HCV-1b, are associated to differences in epidemic features and risk groups, despite sharing similar features in most biological properties. We have analyzed the impact of positive selection on the evolution of these variants using complete genome coding regions, and compared the levels of genetic variability and the distribution of positively selected sites. We have also compared the distributions of positively selected and conserved sites considering different factors such as RNA secondary structure, the presence of different epitopes (antibody, CD4 and CD8), and secondary protein structure...
January 10, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28087398/interaction-of-mal-de-r%C3%A3-o-cuarto-virus-fijivirus-genus-proteins-and-identification-of-putative-factors-determining-viroplasm-formation-and-decay
#3
Gabriela Llauger, Luis Alejandro de Haro, Victoria Alfonso, Mariana Del Vas
Mal de Río Cuarto virus (MRCV) is a member of the Fijivirus genus, within the Reoviridae family, that replicates and assembles in cytoplasmic inclusion bodies called viroplasms. In this study, we investigated interactions between ten MRCV proteins by yeast two-hybrid (Y2H) assays and identified interactions of non-structural proteins P6/P6, P9-2/P9-2 and P6/P9-1. P9-1 and P6 are the major and minor components of the viroplasms respectively, whereas P9-2 is an N-glycosylated membrane protein of unknown function...
January 10, 2017: Virus Research
https://www.readbyqxmd.com/read/28087275/sequence-structure-and-function-relationships-in-flaviviruses-as-assessed-by-evolutive-aspects-of-its-conserved-non-structural-protein-domains
#4
Néli José da Fonseca, Marcelo Querino Lima Afonso, Natan Gonçalves Pedersolli, Lucas Carrijo de Oliveira, Dhiego Souto Andrade, Lucas Bleicher
Flaviviruses are responsible for serious diseases such as dengue, yellow fever, and zika fever. Their genomes encode a polyprotein which, after cleavage, results in three structural and seven non-structural proteins. Homologous proteins can be studied by conservation and coevolution analysis as detected in multiple sequence alignments, usually reporting positions which are strictly necessary for the structure and/or function of all members in a protein family or which are involved in a specific sub-class feature requiring the coevolution of residue sets...
January 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28087229/disease-associated-mutations-identify-a-novel-region-in-human-sting-necessary-for-the-control-of-type-i-interferon-signaling
#5
Isabelle Melki, Yoann Rose, Carolina Uggenti, Lien Van Eyck, Marie-Louise Frémond, Naoki Kitabayashi, Gillian I Rice, Emma M Jenkinson, Anaïs Boulai, Nadia Jeremiah, Marco Gattorno, Sefano Volpi, Olivero Sacco, Suzanne W J Terheggen-Lagro, Harm A W M Tiddens, Isabelle Meyts, Marie-Anne Morren, Petra De Haes, Carine Wouters, Eric Legius, Anniek Corveleyn, Frederic Rieux-Laucat, Christine Bodemer, Isabelle Callebaut, Mathieu P Rodero, Yanick J Crow
BACKGROUND: Gain-of-function mutations in transmembrane protein 173 (TMEM173) encoding stimulator of interferon genes (STING) underlie a recently described type I interferonopathy called STING-associated vasculopathy with onset in infancy (SAVI). OBJECTIVES: We sought to define the molecular and cellular pathology relating to 3 individuals variably exhibiting the core features of the SAVI phenotype including systemic inflammation, destructive skin lesions, and interstitial lung disease...
January 3, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28081264/the-important-role-of-lipid-raft-mediated-attachment-in-the-infection-of-cultured-cells-by-coronavirus-infectious-bronchitis-virus-beaudette-strain
#6
Huichen Guo, Mei Huang, Quan Yuan, Yanquan Wei, Yuan Gao, Lejiao Mao, Lingjun Gu, Yong Wah Tan, Yanxin Zhong, Dingxiang Liu, Shiqi Sun
Lipid raft is an important element for the cellular entry of some viruses, including coronavirus infectious bronchitis virus (IBV). However, the exact role of lipid rafts in the cellular membrane during the entry of IBV into host cells is still unknown. In this study, we biochemically fractionated IBV-infected cells via sucrose density gradient centrifugation after depleting plasma membrane cholesterol with methyl-β-cyclodextrin or Mevastatin. Our results demonstrated that unlike IBV non-structural proteins, IBV structural proteins co-localized with lipid raft marker caveolin-1...
2017: PloS One
https://www.readbyqxmd.com/read/28077791/carcinoma-risk-variant-of-ebna1-deregulates-epstein-barr-virus-episomal-latency
#7
Jayaraju Dheekollu, Kimberly Malecka, Andreas Wiedmer, Henri-Jacques Delecluse, Alan Ks Chiang, Dario C Altieri, Troy E Messick, Paul M Lieberman
Epstein-Barr Virus (EBV) latent infection is a causative co-factor for endemic Nasopharyngeal Carcinoma (NPC). NPC-associated variants have been identified in EBV-encoded nuclear antigen EBNA1. Here, we solve the X-ray crystal structure of an NPC-derived EBNA1 DNA binding domain (DBD) and show that variant amino acids are found on the surface away from the DNA binding interface. We show that NPC-derived EBNA1 is compromised for DNA replication and episome maintenance functions. Recombinant virus containing the NPC EBNA1 DBD are impaired in their ability to immortalize primary B-lymphocytes and suppress lytic transcription during early stages of B-cell infection...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077641/chikungunya-influenza-nipah-and-semliki-forest-chimeric-viruses-with-vesicular-stomatitis-virus-actions-in-the-brain
#8
Anthony N van den Pol, Guochao Mao, Anasuya Chattopadhyay, John K Rose, John N Davis
: Recombinant vesicular stomatitis virus (VSV)-based chimeric viruses that include genes from other viruses show promise as vaccines and oncolytic viruses. However, the critical safety concern is the neurotropic nature conveyed by the VSV glycoprotein. VSVs that include the VSV glycoprotein gene, even in most recombinant attenuated strains, can still show substantial adverse or lethal actions in the brain. Here we test 4 chimeric viruses in the brain including those in which glycoprotein genes from Nipah, chikungunya, or influenza H5N1 viruses were substituted for the VSV glycoprotein gene...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077638/a-conserved-glycine-residue-is-required-for-proper-functioning-of-a-baculovirus-vp39-protein
#9
Susumu Katsuma, Ryuhei Kokusho
: The baculovirus VP39 is a major nucleocapsid protein essential for viral propagation. However, the critical domains or residues of the VP39 protein have not yet been identified. Here, we performed mutagenesis experiments of Bombyx mori nucleopolyhedrovirus (BmNPV) using 5-bromo-2' -deoxyuridine and isolated a BmNPV mutant that produced fewer occlusion bodies than the wild-type virus. This mutant also produced fewer infectious budded viruses (BVs), when compared with the wild-type virus in both cultured cells and B...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077635/virion-structure-of-black-queen-cell-virus-a-common-honeybee-pathogen
#10
Radovan Spurny, Antonín Přidal, Lenka Pálkové, Hoa Khanh Tran Kiem, Joachim R de Miranda, Pavel Plevka
: Viral diseases are a major threat to honeybee (Apis mellifera) populations world-wide and therefore an important factor in reliable crop pollination and food security. Black queen cell virus (BQCV) is the etiological agent of a fatal disease of honeybee queen larvae and pupae. The virus belongs to the genus Triatovirus from the family Dicistroviridae that is part of the order Picornavirales Here we present a crystal structure of BQCV determined to a resolution of 3.4 Å. The virion is formed by sixty copies of each of the major capsid proteins VP1, VP2, and VP3, however there is no density corresponding to a 75-residue-long minor capsid protein VP4 encoded by the BQCV genome...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077633/surveillance-of-bat-coronaviruses-in-kenya-identifies-relatives-of-human-coronaviruses-nl63-and-229e-and-their-recombination-history
#11
Ying Tao, Mang Shi, Christina Chommanard, Krista Queen, Jing Zhang, Wanda Markotter, Ivan V Kuzmin, Edward C Holmes, Suxiang Tong
: Bats harbor a large diversity of coronaviruses (CoVs), several of which are related to zoonotic pathogens that cause severe disease in humans. Our screening of bat samples collected in Kenya during 2007-2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E, suggesting that these two human viruses originate from bats. We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in Triaenops bats and 229E-like viruses circulating in Hipposideros bats, with the break-point located near 5' and 3' end of the spike (S) protein gene...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28076660/influenza-a-virus-ns1-protein-induced-jnk-activation-and-apoptosis-are-not-functionally-linked
#12
Wolfgang Nacken, Viktor Wixler, Christina Ehrhardt, Stephan Ludwig
Expression of the influenza A virus (IAV) non-structural protein NS1 results in the activation of c-Jun N-terminal kinase (JNK). Both NS1 and JNK are involved in apoptosis induction. To investigate their interrelationship, we stably expressed a tamoxifen inducible NS1 oestrogen receptor fusion-protein (NS1ERT) in mammalian cells. Upon tamoxifen stimulation, NS1ERT expressing cells partially rescued the attenuated replication of NS1-deficient IAVs and also inhibited interferon up-regulation, confirming the functional competence of NS1ERT...
January 11, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28076378/p62-pathology-model-in-the-rat-substantia-nigra-with-filamentous-inclusions-and-progressive-neurodegeneration
#13
Kasey L Jackson, Wen-Lang Lin, Sumitra Miriyala, Robert D Dayton, Manikandan Panchatcharam, Kevin J McCarthy, Monica Castanedes-Casey, Dennis W Dickson, Ronald L Klein
One of the proteins most frequently found in neuropathological lesions is the ubiquitin binding protein p62 (sequestosome 1). Post-mortem analysis of p62 is a defining diagnostic marker in several neurodegenerative diseases including amyotrophic lateral sclerosis and inclusion body myositis. Since p62 functions in protein degradation pathways including autophagy, the build-up of p62-positive inclusions suggests defects in protein clearance. p62 was expressed unilaterally in the rat substantia nigra with an adeno-associated virus vector (AAV9) in order to study p62 neuropathology...
2017: PloS One
https://www.readbyqxmd.com/read/28075409/the-hiv-1-vpr-protein-a-multifaceted-target-for-therapeutic-intervention
#14
REVIEW
María Eugenia González
The human immunodeficiency virus type 1 (HIV-1) Vpr protein is an attractive target for antiretroviral drug development. The conservation both of the structure along virus evolution and the amino acid sequence in viral isolates from patients underlines the importance of Vpr for the establishment and progression of HIV-1 disease. While its contribution to virus replication in dividing and non-dividing cells and to the pathogenesis of HIV-1 in many different cell types, both extracellular and intracellular forms, have been extensively studied, its precise mechanism of action nevertheless remains enigmatic...
January 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28073421/-research-advances-in-the-role-of-sphingolipids-in-hcv-and-hbv-life-cycles
#15
J Y Zhang, Z P Duan, J L Zhang, S J Zheng
Sphingolipids and their metabolites are not only important structural molecules of the cell membrane, but also involved in all phases of viral life cycle, including cell adhesion, membrane fusion, viral replication, viral assembly, intracellular transport, protein sorting, and exocytosis. In recent years, sphingolipids have become one of the focuses of lipid research. This article reviews the role of sphingolipids in the life cycles of hepatitis C virus and hepatitis B virus with reference to recent research achievements in China and foreign countries...
December 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28069378/role-of-n-glycosylation-on-zika-virus-e-protein-secretion-viral-assembly-and-infectivity
#16
M Mossenta, S Marchese, M Poggianella, J L Slon Campos, O R Burrone
Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells...
January 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28069291/antagonizing-cytokine-mediated-jak-stat-signaling-by-porcine-reproductive-and-respiratory-syndrome-virus
#17
REVIEW
Liping Yang, Yan-Jin Zhang
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is activated by myriad cytokines, which are involved in regulation of cell growth, proliferation, differentiation, apoptosis, angiogenesis, immunity and inflammatory response. Because of its significance in immune response, JAK-STAT pathway is often targeted by pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV causes reproductive failure in sows and respiratory disease in pigs of all ages...
December 30, 2016: Veterinary Microbiology
https://www.readbyqxmd.com/read/28067914/structure-of-the-immature-zika-virus-at-9-%C3%A3-resolution
#18
Vidya Mangala Prasad, Andrew S Miller, Thomas Klose, Devika Sirohi, Geeta Buda, Wen Jiang, Richard J Kuhn, Michael G Rossmann
The current Zika virus (ZIKV) epidemic is characterized by severe pathogenicity in both children and adults. Sequence changes in ZIKV since its first isolation are apparent when pre-epidemic strains are compared with those causing the current epidemic. However, the residues that are responsible for ZIKV pathogenicity are largely unknown. Here we report the cryo-electron microscopy (cryo-EM) structure of the immature ZIKV at 9-Å resolution. The cryo-EM map was fitted with the crystal structures of the precursor membrane and envelope glycoproteins and was shown to be similar to the structures of other known immature flaviviruses...
January 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28067384/nanocaged-platforms-modification-drug-delivery-and-nanotoxicity-opening-synthetic-cages-to-release-the-tiger
#19
REVIEW
Parham Sahandi Zangabad, Mahdi Karimi, Fatemeh Mehdizadeh, Hedieh Malekzad, Alireza Ghasemi, Sajad Bahrami, Hossein Zare, Mohsen Moghoofei, Amin Hekmatmanesh, Michael R Hamblin
Nanocages (NCs) have emerged as a new class of drug-carriers, with a wide range of possibilities in multi-modality medical treatments and theranostics. Nanocages can overcome such limitations as high toxicity caused by anti-cancer chemotherapy or by the nanocarrier itself, due to their unique characteristics. These properties consist of: (1) a high loading-capacity (spacious interior); (2) a porous structure (analogous to openings between the bars of the cage); (3) enabling smart release (a key to unlock the cage); and (4) a low likelihood of unfavorable immune responses (the outside of the cage is safe)...
January 9, 2017: Nanoscale
https://www.readbyqxmd.com/read/28067229/tubules-of-plant-reoviruses-exploit-tropomodulin-to-regulate-actin-based-tubule-motility-in-insect-vector
#20
Qian Chen, Linghua Zhang, Yanshuang Zhang, Qianzhuo Mao, Taiyun Wei
Plant reoviruses are known to exploit virion-packaging tubules formed by virus-encoding non-structural proteins for viral spread in insect vectors. Tubules are propelled by actin-based tubule motility (ABTM) to overcome membrane or tissue barriers in insect vectors. To further understand which insect factors mediate ABTM, we utilized yeast two-hybrid and bimolecular fluorescence complementation assays to test interactions between tubule protein Pns10 of rice dwarf virus (RDV), a plant reovirus, and proteins of its insect vector, the leafhopper Nephotettix cincticeps...
January 9, 2017: Scientific Reports
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