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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
#1
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 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28410411/hepatitis-c-virus-impairs-natural-killer-cell-activity-via-viral-serine-protease-ns3
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
March 24, 2017: Virus Genes
https://www.readbyqxmd.com/read/28288679/muscovy-duck-reovirus-%C3%AF-ns-protein-triggers-autophagy-enhancing-virus-replication
#9
Yijian Wu, Longping Cui, Erpeng Zhu, Wuduo Zhou, Quanxi Wang, Xiaoping Wu, Baocheng Wu, Yifan Huang, Hung-Jen Liu
BACKGROUND: Muscovy duck reovirus (MDRV) causes high morbidity and mortality in Muscovy ducklings at 10 days old and can persist in an infected flock until the ducklings of 6 weeks old. It shares common physicochemical properties with avian reovirus (ARV) and differs in coding assignment and pathogenicity. The ARV p17 protein has been shown to trigger autophagy via activation multiple signaling pathways, which benefits virus replication. Since MDRV lacks the p17 protein, whether and how MDRV induces autophagy remains unknown...
March 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/28257598/structural-basis-for-dimerization-and-rna-binding-of-avian-infectious-bronchitis-virus-nsp9
#10
Tingting Hu, Cheng Chen, Huiyan Li, Yanshu Dou, Ming Zhou, Deren Lu, Qi Zong, Yulei Li, Cheng Yang, Zhihui Zhong, Namit Singh, Honggang Hu, Rundong Zhang, Haitao Yang, Dan Su
The potential for infection by coronaviruses (CoVs) has become a serious concern with the recent emergence of Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) in the human population. CoVs encode two large polyproteins, which are then processed into 15-16 nonstructural proteins (nsps) that make significant contributions to viral replication and transcription by assembling the RNA replicase complex. Among them, nsp9 plays an essential role in viral replication by forming a homodimer that binds single-stranded RNA...
March 3, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28235682/nuclear-imprisonment-of-host-cellular-mrna-by-nsp1%C3%AE-protein-of-porcine-reproductive-and-respiratory-syndrome-virus
#11
Mingyuan Han, Hanzhong Ke, Qingzhan Zhang, Dongwan Yoo
Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome...
February 18, 2017: Virology
https://www.readbyqxmd.com/read/28202376/structural-features-of-zika-virus-non-structural-proteins-3-and-5-and-its-individual-domains-in-solution-as-well-as-insights-into-ns3-inhibition
#12
Wuan Geok Saw, Ankita Pan, Malathy Sony Subramanian Manimekalai, Gerhard Grüber
Zika virus (ZIKV) has emerged as a pathogen of major health concern. The virus relies on its non-structural protein 5 (NS5) including a methyl-transferase (MTase) and a RNA-dependent RNA polymerase (RdRp) for capping and synthesis of the viral RNA and the nonstructural protein 3 (NS3) with its protease and helicase domain for polyprotein possessing, unwinding dsRNA proceeding replication, and NTPase/RTPase activities. In this study we present for the first time insights into the overall structure of the entire French Polynesia ZIKV NS3 in solution...
February 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28198446/a-mutation-identified-in-neonatal-microcephaly-destabilizes-zika-virus-ns1-assembly-in-vitro
#13
Deping Wang, Cheng Chen, Shengnan Liu, Han Zhou, Kailin Yang, Qi Zhao, Xiaoyun Ji, Chen Chen, Wei Xie, Zefang Wang, Li-Zhi Mi, Haitao Yang
An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1172-352, which forms a head-to-head, symmetric dimer with a unique 14-stranded β-ladder conserved among flaviviruses...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196962/spatial-and-temporal-analysis-of-alphavirus-replication-and-assembly-in-mammalian-and-mosquito-cells
#14
Joyce Jose, Aaron B Taylor, Richard J Kuhn
Sindbis virus (SINV [genus Alphavirus, family Togaviridae]) is an enveloped, mosquito-borne virus. Alphaviruses cause cytolytic infections in mammalian cells while establishing noncytopathic, persistent infections in mosquito cells. Mosquito vector adaptation of alphaviruses is a major factor in the transmission of epidemic strains of alphaviruses. Though extensive studies have been performed on infected mammalian cells, the morphological and structural elements of alphavirus replication and assembly remain poorly understood in mosquito cells...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28151973/a-positive-strand-rna-virus-uses-alternative-protein-protein-interactions-within-a-viral-protease-cofactor-complex-to-switch-between-rna-replication-and-virion-morphogenesis
#15
Danilo Dubrau, M Alejandra Tortorici, Félix A Rey, Norbert Tautz
The viruses of the family Flaviviridae possess a positive-strand RNA genome and express a single polyprotein which is processed into functional proteins. Initially, the nonstructural (NS) proteins, which are not part of the virions, form complexes capable of genome replication. Later on, the NS proteins also play a critical role in virion formation. The molecular basis to understand how the same proteins form different complexes required in both processes is so far unknown. For pestiviruses, uncleaved NS2-3 is essential for virion morphogenesis while NS3 is required for RNA replication but is not functional in viral assembly...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28143984/in-situ-tagged-nsp15-reveals-interactions-with-coronavirus-replication-transcription-complex-associated-proteins
#16
Jeremiah Athmer, Anthony R Fehr, Matthew Grunewald, Everett Clinton Smith, Mark R Denison, Stanley Perlman
Coronavirus (CoV) replication and transcription are carried out in close proximity to restructured endoplasmic reticulum (ER) membranes in replication/transcription complexes (RTC). Many of the CoV nonstructural proteins (nsps) are required for RTC function; however, not all of their functions are known. nsp15 contains an endoribonuclease domain that is conserved in the CoV family. While the enzymatic activity and crystal structure of nsp15 are well defined, its role in replication remains elusive. nsp15 localizes to sites of RNA replication, but whether it acts independently or requires additional interactions for its function remains unknown...
January 31, 2017: MBio
https://www.readbyqxmd.com/read/28142057/the-effect-of-classical-swine-fever-virus-ns5a-and-ns5a-mutants-on-oxidative-stress-and-inflammatory-response-in-swine-testicular-cells
#17
Wang Dong, Huifang Lv, Yifan Wang, Xiaomeng Li, Cheng Li, Lu Wang, Chengbao Wang, Kangkang Guo, Yanming Zhang
Infection with classical swine fever virus (CSFV) results in highly significant economic losses; this infection is characterized by being highly contagious and accompanied by hyperthermia and systemic bleeding. Oxidative stress (OS) plays a critical role in the pathological process of viral infection. The function of the nonstructural protein 5A (NS5A) in the pathogenesis of CSFV has not been completely understood. Here, OS and the inflammatory response were studied with NS5A and substitution mutants in swine testicular (ST) cells...
January 13, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28131854/a-structural-view-of-the-rna-dependent-rna-polymerases-from-the-flavivirus-genus
#18
REVIEW
Guoliang Lu, Peng Gong
The RNA-dependent RNA polymerase (RdRP) from the Flavivirus genus is naturally fused to a methyltransferase (MTase), and the full-length protein is named nonstructural protein 5 (NS5). Similar to polymerases from other RNA viruses, the flavivirus RdRP has an encircled human right hand architecture with palm, fingers, and thumb domains surrounding its polymerase active site. In contrast to primer-dependent RdRPs that have a spacious front channel to accommodate the template-product RNA duplex, the flavivirus RdRP has a priming element as a thumb domain insertion, partially occupying the front channel to facilitate the de novo initiation process...
January 25, 2017: Virus Research
https://www.readbyqxmd.com/read/28122984/parvovirus-expresses-a-small-noncoding-rna-that-plays-an-essential-role-in-virus-replication
#19
Zekun Wang, Weiran Shen, Fang Cheng, Xuefeng Deng, John F Engelhardt, Ziying Yan, Jianming Qiu
Human bocavirus 1 (HBoV1) belongs to the species Primate bocaparvovirus of the genus Bocaparvovirus of the Parvoviridae family. HBoV1 causes acute respiratory tract infections in young children and has a selective tropism for the apical surface of well-differentiated human airway epithelia (HAE). In this study, we identified an additional HBoV1 gene, bocavirus-transcribed small noncoding RNA (BocaSR), within the 3' noncoding region (nucleotides [nt] 5199 to 5338) of the viral genome of positive sense. BocaSR is transcribed by RNA polymerase III (Pol III) from an intragenic promoter at levels similar to that of the capsid protein-coding mRNA and is essential for replication of the viral DNA in both transfected HEK293 and infected HAE cells...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28112593/oral-combination-vaccine-comprising-bifidobacterium-displaying-hepatitis-c-virus-nonstructural-protein-3-and-interferon-%C3%AE-induces-strong-cellular-immunity-specific-to-nonstructural-protein-3-in-mice
#20
Koichi Kitagawa, Chika Omoto, Tsugumi Oda, Ayame Araki, Hiroki Saito, Katsumi Shigemura, Takane Katayama, Hak Hotta, Toshiro Shirakawa
We previously generated an oral hepatitis C virus (HCV) vaccine using Bifidobacterium displaying the HCV nonstructural protein 3 (NS3) polypeptide. NS3-specific cellular immunity is important for viral clearance and recovery from HCV infection. In this study, we enhanced the cellular immune responses induced by our oral HCV vaccine, Bifidobacterium longum 2165 (B. longum 2165), by combining interferon-α (IFN-α) as an adjuvant with the vaccine in a mouse experimental model. IFN-α is a widely used cytokine meeting the standard of care (SOC) for HCV infection and plays various immunoregulatory roles...
April 2017: Viral Immunology
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