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viral nonstructural protein

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https://www.readbyqxmd.com/read/28650973/interferon-signaling-in-peromyscus-leucopus-confers-a-potent-and-specific-restriction-to-vector-borne-flaviviruses
#1
Adaeze O Izuogu, Kristin L McNally, Stephen E Harris, Brian H Youseff, John B Presloid, Christopher Burlak, Jason Munshi-South, Sonja M Best, R Travis Taylor
Tick-borne flaviviruses (TBFVs), including Powassan virus and tick-borne encephalitis virus cause encephalitis or hemorrhagic fevers in humans with case-fatality rates ranging from 1-30%. Despite severe disease in humans, TBFV infection of natural rodent hosts has little noticeable effect. Currently, the basis for resistance to disease is not known. We hypothesize that the coevolution of flaviviruses with their respective hosts has shaped the evolution of potent antiviral factors that suppress virus replication and protect the host from lethal infection...
2017: PloS One
https://www.readbyqxmd.com/read/28634750/t135i-substitution-in-the-nonstructural-protein-2c-enhances-foot-and-mouth-disease-virus-replication
#2
Tiangang Yuan, Haiwei Wang, Chen Li, Decheng Yang, Guohui Zhou, Li Yu
The foot-and-mouth disease virus (FMDV) nonstructural protein 3A plays an important role in viral replication, virulence, and host range. It has been shown that deletions of 10 or 19-20 amino acids in the C-terminal half of 3A attenuate serotype O and C FMDVs, which replicate poorly in bovine cells but normally in porcine-derived cells, and the C-terminal half of 3A is not essential for serotype Asia1 FMDV replication in BHK-21 cells. In this study, we constructed a 3A deletion FMDV mutant based on a serotype O FMDV, the wild-type virus O/YS/CHA/05, with a 60-amino acid deletion in the 3A protein sequence, between residues 84 and 143...
June 20, 2017: Virus Genes
https://www.readbyqxmd.com/read/28592628/chemiluminescence-immunoassay-for-the-detection-of-antibodies-against-the-2c-and-3abc-nonstructural-proteins-induced-by-infecting-pigs-with-the-foot-and-mouth-disease-virus
#3
Zezhong Liu, Junjun Shao, Furong Zhao, Guangqing Zhou, Shandian Gao, Wei Liu, Jianliang Lv, Xiumei Li, Yangfan Li, Huiyun Chang, Yongguang Zhang
The potential diagnostic value of chemiluminescence immunoassays (CLIAs) has been accepted in recent years, although its use for foot-and-mouth disease (FMD) diagnostics has not been reported. Full-length 3ABC and 2C proteins were expressed in bacteria and purified by affinity chromatography to develop a rapid and accurate approach to distinguish pigs infected with foot-and-mouth disease virus (FMDV) from vaccinated pigs (DIVA). The recombinant proteins were then used as antigens to develop two CLIAs for the detection of antibodies against nonstructural viral proteins...
June 7, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28580734/sars-unique-fold-in-the-rousettus-bat-coronavirus-hku9
#4
Robert G Hammond, Xuan Tan, Margaret A Johnson
The coronavirus nonstructural protein 3 (nsp3) is a multifunctional protein that comprises multiple structural domains. This protein assists viral polyprotein cleavage, host immune interference, and may play other roles in genome replication or transcription. Here, we report the solution NMR structure of a protein from the "SARS-unique region" of the bat coronavirus HKU9. The protein contains a frataxin fold or double-wing motif, which is an α + β fold that is associated with protein/protein interactions, DNA binding, and metal ion binding...
June 5, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28566381/hepatitis-c-virus-subverts-human-choline-kinase-%C3%AE-to-bridge-pi4kiii%C3%AE-and-ns5a-and-upregulates-pi4kiii%C3%AE-activation-thereby-promoting-the-translocation-of-the-ternary-complex-to-the-er-for-viral-replication
#5
Mun-Teng Wong, Steve S Chen
In this study, we elucidated the mechanism by which human choline kinase-α (hCKα) interacts with nonstructural protein (NS)5A and phosphatidylinositol-4-kinase (PI4K)IIIα, the lipid kinase crucial for maintaining the integrity of virus-induced membranous webs, and modulates hepatitis C virus (HCV) replication. hCKα activity positively modulated PI-4-phosphate (PI4P) levels in HCV-expressing cells, and hCKα-mediated PI4P accumulation was abolished by AL-9, a PI4KIIIα-specific inhibitor. hCKα colocalized with NS5A and PI4KIIIα or PI4P, NS5A expression increased hCKα and PI4KIIIα colocalization, and hCKα formed a ternary complex with PI4KIIIα and NS5A, supporting the functional interplay of hCKα with PI4KIIIα and NS5A...
May 31, 2017: Journal of Virology
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
#6
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
#7
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
#8
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...
June 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
#9
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/28501618/assessing-activity-of-hepatitis-a-virus-3c-protease-using-a-cyclized-luciferase-based-biosensor
#10
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/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
#11
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/28446677/variable-inhibition-of-zika-virus-replication-by-different-wolbachia-strains-in-mosquito-cell-cultures
#12
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/28410427/tcr-stimulation-strength-is-inversely-associated-with-establishment-of-functional-brain-resident-memory-cd8-t-cells-during-persistent-viral-infection
#13
Saumya Maru, Ge Jin, Todd D Schell, Aron E Lukacher
Establishing functional tissue-resident memory (TRM) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28410411/hepatitis-c-virus-impairs-natural-killer-cell-activity-via-viral-serine-protease-ns3
#14
Chang Mo Yang, Joo Chun Yoon, Jeon Han Park, Jae Myun Lee
Hepatitis C virus (HCV) infection is characterized by a high frequency of chronic cases owing to the impairment of innate and adaptive immune responses. The modulation of natural killer (NK) cell functions by HCV leads to an impaired innate immune response. However, the underling mechanisms and roles of HCV proteins in this immune evasion are controversial, especially in the early phase of HCV infection. To investigate the role of HCV nonstructural proteins especially NS3 in the impairment of NK functions, NK cells were isolated from the PBMCs by negative selection...
2017: PloS One
https://www.readbyqxmd.com/read/28403441/clinical-and-laboratory-diagnosis-of-dengue-virus-infection
#15
REVIEW
David A Muller, Alexandra C I Depelsenaire, Paul R Young
Infection with any of the 4 dengue virus serotypes results in a diverse range of symptoms, from mild undifferentiated fever to life-threatening hemorrhagic fever and shock. Given that dengue virus infection elicits such a broad range of clinical symptoms, early and accurate laboratory diagnosis is essential for appropriate patient management. Virus detection and serological conversion have been the main targets of diagnostic assessment for many years, however cross-reactivity of antibody responses among the flaviviruses has been a confounding issue in providing a differential diagnosis...
March 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28381575/filamentous-structures-induced-by-a-phytoreovirus-mediate-viral-release-from-salivary-glands-in-its-insect-vector
#16
Qianzhuo Mao, Zhengfeng Liao, Jiajia Li, Yuyan Liu, Wei Wu, Hongyan Chen, Qian Chen, Dongsheng Jia, Taiyun Wei
Numerous viral pathogens are persistently transmitted by insect vectors and cause agricultural or health problems. These viruses circulate in the vector body, enter the salivary gland, and then are released into the apical plasmalemma-lined cavities where saliva is stored. The cavity plasmalemma of vector salivary glands thus represents the last membrane barrier for viral transmission. Here, we report a novel mechanism used by a persistent virus to overcome this essential barrier. We observed that the infection by rice gall dwarf virus (RGDV), a species of the genus Phytoreovirus in the family Reoviridae, induced to form virus-associated filaments constructed by viral nonstructural protein Pns11 within the salivary glands of its leafhopper vector Recilia dorsalis Such filaments attached to actin-based apical plasmalemma and induced an exocytosis-like process for viral release into vector salivary gland cavities, through a direct interaction of Pns11 of RGDV and actin of R...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28373913/zika-virus-evades-interferon-mediated-antiviral-response-through-the-co-operation-of-multiple-nonstructural-proteins-in-vitro
#17
Yaoxing Wu, Qingxiang Liu, Jie Zhou, Weihong Xie, Cheng Chen, Zefang Wang, Haitao Yang, Jun Cui
Type I interferon (IFN) serves as the first line of defense against invading pathogens. Inhibition of IFN-triggered signaling cascade by Zika virus (ZIKV) plays a critical role for ZIKV to evade antiviral responses from host cells. Here we demonstrate that ZIKV nonstructural proteins NS1, NS4B and NS2B3 inhibit the induction of IFN and downstream IFN-stimulated genes through diverse strategies. NS1 and NS4B of ZIKV inhibit IFNβ signaling at TANK-binding kinase 1 level, whereas NS2B-NS3 of ZIKV impairs JAK-STAT signaling pathway by degrading Jak1 and reduces virus-induced apoptotic cell death...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28345656/structure-and-function-of-the-zika-virus-full-length-ns5-protein
#18
Baoyu Zhao, Guanghui Yi, Fenglei Du, Yin-Chih Chuang, Robert C Vaughan, Banumathi Sankaran, C Cheng Kao, Pingwei Li
The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28344409/outbreak-of-foot-and-mouth-disease-and-peste-des-petits-ruminants-in-sheep-flock-imported-for-immediate-slaughter-in-riyadh
#19
M A Mahmoud, S A Galbat
AIM: To detect and identify the causative agent or agents of the following clinical symptoms which were fever, lack of appetite, salivation, vesiculation, erosions of the buccal mucosa, nose, and feet. The signs vary from mild to severe. The mortality rate of the disease is high. The morbidity rate reaches up to 100%. Sheep also show bloody diarrhea and rapid respiration. Sheep flock resident in El-Kharje Governorate. MATERIALS AND METHODS: A total of 50 serum samples and 50 buffy coat samples were collected from Marino sheep flock suffered from high mortalities, fever, lameness, diarrhea, stomatitis, and respiratory distress...
February 2017: Veterinary World
https://www.readbyqxmd.com/read/28341934/molecular-chaperone-jiv-promotes-the-rna-replication-of-classical-swine-fever-virus
#20
Kangkang Guo, Haimin Li, Xuechao Tan, Mengmeng Wu, Qizhuang Lv, Wei Liu, Yanming Zhang
The nonstructural protein 2 (NS2) of classical swine fever virus (CSFV) is a self-splicing ribozyme wherein the precursor protein NS2-3 is cleaved, and the cleavage efficiency of NS2-3 is crucial to the replication of viral RNA. However, the proteolytic activity of NS2 autoprotease may be achieved through a cellular chaperone called J-domain protein interacting with viral protein (Jiv) or its fragment Jiv90, as evidence suggests that Jiv is required for the proper functioning of the NS2 protein of bovine viral diarrhea virus...
June 2017: Virus Genes
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