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https://www.readbyqxmd.com/read/29331676/identification-of-novel-amino-acid-residues-of-influenza-virus-pa-x-that-are-important-for-pa-x-shutoff-activity-by-using-yeast
#1
Kohei Oishi, Seiya Yamayoshi, Yoshihiro Kawaoka
The influenza A virus protein PA-X comprises an N-terminal PA region and a C-terminal PA-X-specific region. PA-X suppresses host gene expression, termed shutoff, via mRNA cleavage. Although the endonuclease active site in the N-terminal PA region of PA-X and basic amino acids in the C-terminal PA-X-specific region are known to be important for PA-X shutoff activity, other amino acids may also play a role. Here, we used yeast to identify novel amino acids of PA-X that are important for PA-X shutoff activity...
January 10, 2018: Virology
https://www.readbyqxmd.com/read/29330069/conformation-and-trimer-association-of-the-transmembrane-domain-of-the-parainfluenza-virus-fusion-protein-in-lipid-bilayers-from-solid-state-nmr-insights-into-the-sequence-determinants-of-trimer-structure-and-fusion-activity
#2
Myungwoon Lee, Hongwei Yao, Byungsu Kwon, Alan J Waring, Peter Ruchala, Chandan Singh, Mei Hong
Enveloped viruses enter cells by using their fusion proteins to merge the virus lipid envelope and the cell membrane. While crystal structures of the water-soluble ectodomains of many viral fusion proteins have been determined, the structure and assembly of the C-terminal transmembrane domain (TMD) remains poorly understood. Here we use solid-state NMR to determine the backbone conformation and oligomeric structure of the TMD of the parainfluenza virus 5 (PIV5) fusion protein. 13C chemical shifts indicate that the central leucine-rich segment of the TMD is α-helical in POPC/cholesterol membranes and POPE membranes, while the Ile- and Val-rich termini shift to the β-strand conformation in the POPE membrane...
January 9, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29329879/mir-134-modulates-chronic-stress-induced-structural-plasticity-and-depression-like-behaviors-via-downregulation-of-limk1-cofilin-signaling-in-rats
#3
Cuiqin Fan, Xiuzhi Zhu, Qiqi Song, Peng Wang, Zhuxi Liu, Shu Yan Yu
Increasing evidence has suggested that depression is a neuropsychiatric condition associated with neuroplasticity within specific brain regions. However, the mechanisms by which neuroplasticity exerts its effects in depression remain largely uncharacterized. In the present study we show that chronic stress effectively induces depression-like behaviors in rats, an effect which was associated with structural changes in dendritic spines and synapse abnormalities within neurons of the ventromedial prefrontal cortex (vmPFC)...
January 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29329682/feline-coronavirus-insights-into-viral-pathogenesis-based-on-the-spike-protein-structure-and-function
#4
Javier A Jaimes, Gary R Whittaker
Feline coronavirus (FCoV) is an etiological agent that causes a benign enteric illness and the fatal systemic disease feline infectious peritonitis (FIP). The FCoV spike (S) protein is considered the viral regulator for binding and entry to the cell. This protein is also involved in FCoV tropism and virulence, as well as in the switch from enteric disease to FIP. This regulation is carried out by spike's major functions: receptor binding and virus-cell membrane fusion. In this review, we address important aspects in FCoV genetics, replication and pathogenesis, focusing on the role of S...
January 9, 2018: Virology
https://www.readbyqxmd.com/read/29329078/schmallenberg-virus-non-structural-protein-nsm-intracellular-distribution-and-role-of-non-hydrophobic-domains
#5
Franziska Kraatz, Kerstin Wernike, Sven Reiche, Andrea Aebischer, Ilona Reimann, Martin Beer
Schmallenberg virus (SBV) induces fetal malformation, abortions and stillbirth in ruminants. While the non-structural protein NSs is a major virulence factor, the biological function of NSm, the second non-structural protein which consists of three hydrophobic transmembrane (I, III, V) and two non-hydrophobic regions (II, IV), is still unknown. Here, a series of NSm mutants displaying deletions of nearly the entire NSm or of the non-hydrophobic domains was generated and the intracellular distribution of NSm was assessed...
January 9, 2018: Virology
https://www.readbyqxmd.com/read/29325885/9-aminoacridine-based-agents-impair-the-bovine-viral-diarrhea-virus-bvdv-replication-targeting-the-rna-dependent-rna-polymerase-rdrp
#6
Roberta Loddo, Valeria Francesconi, Erik Laurini, Silvia Boccardo, Suzana Aulic, Maurizio Fermeglia, Sabrina Pricl, Michele Tonelli
Bovine viral diarrhea virus (BVDV) infection is still a plague that causes important livestock pandemics. Despite the availability of vaccines against BVDV, and the implementation of massive eradication or control programs, this virus still constitutes a serious agronomic burden. Therefore, the alternative approach to combat Pestivirus infections, based on the development of antiviral agents that specifically inhibit the replication of these viruses, is of preeminent actuality and importance. Capitalizing from a long-standing experience in antiviral drug design and development, in this work we present and characterize a series of small molecules based on the 9-aminoacridine scaffold that exhibit potent anti-BVDV activity coupled with low cytotoxicity...
January 4, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29324680/phylogenetic-analysis-and-characterization-of-a-sporadic-isolate-of-equine-influenza-a-h3n8-from-an-unvaccinated-horse-in-2015
#7
Chithra C Sreenivasan, Sunayana S Jandhyala, Sisi Luo, Ben M Hause, Milton Thomas, David E B Knudsen, Pamela Leslie-Steen, Travis Clement, Stephanie E Reedy, Thomas M Chambers, Jane Christopher-Hennings, Eric Nelson, Dan Wang, Radhey S Kaushik, Feng Li
Equine influenza, caused by the H3N8 subtype, is a highly contagious respiratory disease affecting equid populations worldwide and has led to serious epidemics and transboundary pandemics. This study describes the phylogenetic characterization and replication kinetics of recently-isolated H3N8 virus from a nasal swab obtained from a sporadic case of natural infection in an unvaccinated horse from Montana, USA. The nasal swab tested positive for equine influenza by Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR)...
January 11, 2018: Viruses
https://www.readbyqxmd.com/read/29322425/production-of-recombinant-killer-immunoglobulin-like-receptors-for-crystallography-and-luminex-based-assays
#8
Phillip Pymm, Julian P Vivian
The killer immunoglobulin-like receptors (KIR) are a highly diverse family of cell-surface receptors that are of importance to the effector function of Natural Killer cells. KIR have been implicated in the detection and clearance of malignantly transformed cells and in the immune-control of viruses including HIV, HCV and CMV. Recently, the mismatching of donor and recipient KIR has been demonstrated to improve success of hematopoietic stem cell transplantation treatments of leukemias. Due to the high degree of diversity amongst the KIR, a number of strategies are required for the production of recombinant protein for medical, biochemical and structural applications...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29322096/dystrophin-gene-expression-and-intracellular-calcium-changes-in-the-giant-freshwater-prawn-macrobrachium-rosenbergii-in-response-to-white-spot-symptom-disease-infection
#9
Anees Fathima Noor, Tze Chiew Christie Soo, Farhana Mohd Ghani, Zee Hong Goh, Li Teng Khoo, Subha Bhassu
Background: Dystrophin, an essential protein functional in the maintenance of muscle structural integrity is known to be responsible for muscle deterioration during white spot syndrome virus (WSSV) infection among prawn species. Previous studies have shown the upregulation of dystrophin protein in Macrobrachium rosenbergii (the giant freshwater prawn) upon white spot syndrome virus (WSSV) infection. The literature has also suggested the important role of calcium ion alterations in causing such muscle diseases...
December 2017: Heliyon
https://www.readbyqxmd.com/read/29321964/introduction-of-h2c2-type-zinc-binding-residues-into-hiv-2-vpr-increases-its-expression-level
#10
Ryoko Koga, Minami Yamamoto, Halil Ibrahim Ciftci, Masami Otsuka, Mikako Fujita
Human immunodeficiency virus type 2 has two structurally similar proteins, Vpx and Vpr. Vpx degrades the host anti-viral protein SAMHD1 and is expressed at high levels, while Vpr is responsible for cell cycle arrest and is expressed at much lower levels. We constructed a Vpr mutant with a high level of expression by replacing the amino acids HHCR/HHCH with a putative H2C2-type zinc-binding site that is carried by Vpx. Our finding suggests that during the evolution of Vpr and Vpx, zinc-binding likely became a mechanism for regulating their expression levels...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29321328/activities-of-thrombin-and-factor-xa-are-essential-for-replication-of-hepatitis-e-virus-and-are-possibly-implicated-in-the-orf1-polyprotein-processing
#11
Gayatri D Kanade, Kunal D Pingale, Yogesh A Karpe
Hepatitis E virus (HEV) is a clinically important positive-sense RNA virus. The ORF1 of HEV encodes a non-structural polyprotein of 1693 amino acids. It is not clear whether the ORF1 polyprotein is processed into distinct enzymatic domains. Many researchers have attempted to understand the mechanisms of pORF1 processing. However, these studies gave varied results and could never convincingly establish the mechanism of pORF1 processing. In this study, we demonstrated the possible role of thrombin and factor Xa in pORF1 processing...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321325/the-identification-and-characterization-of-sindbis-virus-rna-host-protein-interactions
#12
Autumn T LaPointe, Natasha N Gebhart, Megan E Meller, Richard W Hardy, Kevin J Sokoloski
Arthropod-borne viruses, such as the members of genus Alphavirus, are a significant concern to global public health. As obligate intracellular pathogens, RNA viruses must interact with the host cell machinery to establish, and complete, their viral lifecycles. Despite considerable efforts to define the host/pathogen interactions essential for alphaviral replication, an unbiased and inclusive assessment of alphaviral RNA:protein interactions has not been undertaken. Moreover, the biological and molecular importance of these interactions, in the full context of their molecular function as RNA-binding proteins, has not been fully realized...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321321/functional-analysis-of-the-dengue-virus-genome-using-an-insertional-mutagenesis-screen
#13
Jeffrey W Perry, Yanhua Chen, Elizabeth Speliotes, Andrew W Tai
In the last few decades, dengue virus, an arbovirus, has spread to over 120 countries. Although a vaccine has been approved in some countries, limitations on its effectiveness, and a lack of effective antiviral treatments reinforce the need for additional research. The functions of several viral nonstructural proteins are essentially unknown. To better understand the functions of these proteins and thus dengue virus pathogenesis, we embarked on a genome wide transposon mutagenesis screen with Next Generation Sequencing to determine sites in the viral genome that tolerate 15 nucleotide insertions...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321319/non-structural-protein-%C3%AF-1s-is-required-for-optimal-reovirus-protein-expression
#14
Matthew B Phillips, Johnasha D Stuart, Emily J Simon, Karl W Boehme
Reovirus non-structural protein σ1s is required for the establishment of viremia and hematogenous viral dissemination. However, the function of the σ1s protein during the reovirus replication cycle is not known. In this study, we found that σ1s was required for efficient reovirus replication in SV40-immortalized endothelial cells (SVECs), mouse embryonic fibroblasts, human umbilical vein endothelial cells (HUVECs), and T84 human colonic epithelial cells. In each of these cell lines, wild type reovirus produced substantially higher viral titers than a σ1s-deficient mutant...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321318/viperin-restricts-zika-virus-and-tick-borne-encephalitis-virus-replication-by-targeting-ns3-for-proteasomal-degradation
#15
Christakis Panayiotou, Richard Lindqvist, Chaitanya Kurhade, Kirstin Vonderstein, Jenny Pasto, Karin Edlund, Arunkumar S Upadhyay, Anna K Överby
Flaviviruses are arthropod-borne viruses that constitute a major global health problem, with millions of human infections annually. Their pathogenesis ranges from mild illness to severe manifestations such as hemorrhagic fever and fatal encephalitis. Type I interferons (IFNs) are induced in response to viral infection, and stimulate the expression of interferon-stimulated genes (ISGs), including that encoding viperin (virus-inhibitory protein, endoplasmic reticulum-associated, IFN-inducible), which shows antiviral activity against a broad spectrum of viruses including several flaviviruses...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321316/two-residues-in-nsp9-contribute-to-the-enhanced-replication-and-pathogenicity-of-highly-pathogenic-porcine-reproductive-and-respiratory-syndrome-virus
#16
Kuan Zhao, Jia-Cong Gao, Jun-Yao Xiong, Jin-Chao Guo, Yong-Bo Yang, Cheng-Gang Jiang, Yan-Dong Tang, Zhi-Jun Tian, Xue-Hui Cai, Guang-Zhi Tong, Tong-Qing An
Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) possesses greater replicative capacity and pathogenicity than classical PRRSV. However, the factors that lead to enhanced replication and pathogenicity remain unclear. In our study, an alignment of all available full-length sequences of North-American type PRRSVs (n = 204) revealed two consistent amino acid mutations that differed between HP-PRRSV and classical PRRSV and were located at positions 519 and 544 in non-structural protein 9...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321309/specific-mutations-in-the-pb2-protein-of-influenza-a-virus-compensate-for-the-lack-of-efficient-ifn-antagonism-of-the-ns1-protein-of-bat-influenza-a-like-viruses
#17
Teresa Aydillo, Juan Ayllon, Amzie Pavlisin, Carles Martinez-Romero, Shashank Tripathi, Ignacio Mena, Andrés Moreira-Soto, Amanda Vicente-Santos, Eugenia Corrales-Aguilar, Martin Schwemmle, Adolfo García-Sastre
Recently, two new influenza A-like viruses have been discovered in bats, HL17NL10 and HL18NL11. The hemagglutinin-like (HL) and neuraminidase like (NL) proteins of these viruses lack hemagglutination and neuraminidase activities despite their sequence and structural homologies with the HA and NA proteins of conventional influenza A virus. We now have investigated whether the NS1 proteins of HL17NL10 and HL18NL11 viruses can functionally substitute the NS1 protein of a conventional influenza A virus. For this purpose we generated recombinant influenza A/PR8/34 (PR8) H1N1 viruses containing the NS1 protein of PR8 WT, HL17NL10 and HL18NL11 viruses...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29319335/astrovirology-viruses-at-large-in-the-universe
#18
Aaron J Berliner, Tomohiro Mochizuki, Kenneth M Stedman
Viruses are the most abundant biological entities on modern Earth. They are highly diverse both in structure and genomic sequence, play critical roles in evolution, strongly influence terran biogeochemistry, and are believed to have played important roles in the origin and evolution of life. However, there is yet very little focus on viruses in astrobiology. Viruses arguably have coexisted with cellular life-forms since the earliest stages of life, may have been directly involved therein, and have profoundly influenced cellular evolution...
January 10, 2018: Astrobiology
https://www.readbyqxmd.com/read/29317308/molecular-characterization-of-caspase-members-and-expression-response-to-nervous-necrosis-virus-outbreak-in-pacific-cod
#19
Ming-Guang Mao, Jie-Lan Jiang, Zhi-Qiang Jiang, Rui-Ting Liu, Qi-Ya Zhang, Jian-Fang Gui
Multiple functions of caspases include normal cell turnover, proper development and function of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell injury. During artificial propagation of Pacific cod, Gadus macrocephalus, high mortality occurred during early development stages. Here, we performed various analyses on the cDNA and protein sequences of six different G. macrocephalus caspases namely GmCasp3, 6, 7, 8, 9 and 10, and tried to investigate the contributions of caspase family to the development and Nervous Necrosis Virus (NNV) resistance...
January 6, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29317151/structure-activity-relationships-of-cryptopleurine-analogs-with-e-ring-modifications-as-anti-hepatitis-c-virus-agents
#20
Ying Wang, Shao-Ru Chen, Xiaoming Yang, Kuo-Hsiung Lee, Yung-Chi Cheng
The tylophorine analog rac-cryptopleurine exhibited potent anti-hepatitis C virus (HCV) activity through allosteric regulation of ATPase activity of heat shock cognate protein 70 (Hsc70). We evaluated the impact of modifications on the E-ring of rac-cryptopleurine to the inhibitory activity against HCV replication and regulation of ATPase activity of Hsc70. Cryptopleurine analog YXM-110 with a 13α-hydroxyl group maintained activity against HCV and promoted ATP/ADP turnover of Hsc70; however, compounds with hydroxyl groups at other positions or with other orientations (YXM-109, YXM-139, and YXM-140) did not exhibit similar activities...
December 20, 2017: Bioorganic & Medicinal Chemistry
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