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https://www.readbyqxmd.com/read/28904127/therapeutic-effects-of-monoclonal-antibody-against-dengue-virus-ns1-in-a-stat1-knockout-mouse-model-of-dengue-infection
#1
Shu-Wen Wan, Pei-Wei Chen, Chin-Yu Chen, Yen-Chung Lai, Ya-Ting Chu, Chia-Yi Hung, Han Lee, Hsuan Franziska Wu, Yung-Chun Chuang, Jessica Lin, Chih-Peng Chang, Shuying Wang, Ching-Chuan Liu, Tzong-Shiann Ho, Chiou-Feng Lin, Chien-Kuo Lee, Betty A Wu-Hsieh, Robert Anderson, Trai-Ming Yeh, Yee-Shin Lin
Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti-DENV NS1 Ab-mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28893180/annexin-a2-anxa2-interacts-with-nonstructural-protein-1-and-promotes-the-replication-of-highly-pathogenic-h5n1-avian-influenza-virus
#2
Yong Ma, Jiashan Sun, Linlin Gu, Hongmei Bao, Yuhui Zhao, Lin Shi, Wei Yao, Guobin Tian, Xiurong Wang, Hualan Chen
BACKGROUND: Non-structural protein 1 (NS1) is a multifunctional protein and a crucial regulatory factor in the replication and pathogenesis of avian influenza virus (AIV). Studies have shown that NS1 can interact with a variety of host proteins to modulate the viral life cycle. We previously generated a monoclonal antibody against NS1 protein; In the current research study, using this antibody, we immunoprecipitated host proteins that interact with NS1 to better understand the roles played by NS1 in communications between virus and host...
September 11, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28882564/searching-for-synergy-identifying-optimal-antiviral-combination-therapy-using-hepatitis-c-virus-hcv-agents-in-a-replicon-system
#3
Justin J Pomeroy, George L Drusano, Jaime L Rodriquez, Ashley N Brown
Direct acting antiviral agents (DAAs) are potent inhibitors of Hepatitis C virus (HCV) that have revolutionized the treatment landscape for this important viral disease. There are currently four classes of DAAs that inhibit HCV replication via distinct mechanisms of action: nonstructural protein (NS) 3/4a protease inhibitors, NS5A inhibitors, NS5B nucleoside polymerase inhibitors, and NS5B non-nucleoside polymerase inhibitors. Combination therapy with two or more DAAs has great potential to further enhance antiviral potency...
September 4, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28876240/crystal-structures-of-the-methyltransferase-and-helicase-from-the-zika-1947-mr766-uganda-strain
#4
Malgorzata Bukrejewska, Urszula Derewenda, Malwina Radwanska, Daniel A Engel, Zygmunt S Derewenda
Two nonstructural proteins encoded by Zika virus strain MR766 RNA, a methyltransferase and a helicase, were crystallized and their structures were solved and refined at 2.10 and 2.01 Å resolution, respectively. The NS5 methyltransferase contains a bound S-adenosyl-L-methionine (SAM) co-substrate. The NS3 helicase is in the apo form. Comparison with published crystal structures of the helicase in the apo, nucleotide-bound and single-stranded RNA (ssRNA)-bound states suggests that binding of ssRNA to the helicase may occur through conformational selection rather than induced fit...
September 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28874549/molecular-basis-of-mammalian-transmissibility-of-avian-h1n1-influenza-viruses-and-their-pandemic-potential
#5
Mark Zanin, Sook-San Wong, Subrata Barman, Challika Kaewborisuth, Peter Vogel, Adam Rubrum, Daniel Darnell, Atanaska Marinova-Petkova, Scott Krauss, Richard J Webby, Robert G Webster
North American wild birds are an important reservoir of influenza A viruses, yet the potential of viruses in this reservoir to transmit and cause disease in mammals is not well understood. Our surveillance of avian influenza viruses (AIVs) at Delaware Bay, USA, revealed a group of similar H1N1 AIVs isolated in 2009, some of which were airborne-transmissible in the ferret model without prior adaptation. Comparison of the genomes of these viruses revealed genetic markers of airborne transmissibility in the Polymerase Basic 2 (PB2), PB1, PB1-F2, Polymerase Acidic-X (PA-X), Nonstructural Protein 1 (NS1), and Nuclear Export Protein (NEP) genes...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28854955/identification-of-two-mutation-sites-in-spike-and-envelope-proteins-mediating-optimal-cellular-infection-of-porcine-epidemic-diarrhea-virus-from-different-pathways
#6
Min Sun, Jiale Ma, Zeyanqiu Yu, Zihao Pan, Chengping Lu, Huochun Yao
Entry of the α-coronavirus porcine epidemic diarrhea virus (PEDV) requires specific proteases to activate spike (S) protein for the membrane fusion of the virion to the host cell following receptor binding. Herein, PEDV isolate 85-7 could proliferate and induce cell-cell fusion in a trypsin independent manner on Vero cells, and eight homologous mutation strains were screened by continuous proliferation in the absence of trypsin on Vero cells. According to the whole genome sequence comparative analysis, we identified four major variations located in nonstructural protein 2, S, open reading frame 3, and envelope (E) genes, respectively...
August 30, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28853260/-effect-of-porcine-epidemic-diarrhea-virus-nsp1-on-type-%C3%A2-interferon-response
#7
Xiaoxue Wang, Hongjie Li, Yongtao Li, Dongsheng Gao, Lu Chen, Hongtao Chang, Hongying Liu, Chuanqing Wang, Jun Zhao
Porcine epidemic diarrhea virus (PEDV) inhibits the host typeⅠinterferon and cellular antiviral response, but its inhibition mechanism is unclear, and the roles of PEDV nonstructural proteins in regulating typeⅠinterferon responses have been seldom studied. To study the effect of nsp1 on typeⅠinterferon response, nsp1 gene was cloned into a eukaryotic expression vector pCAGGS. The expression of nsp1 in transfected cells was determined by Western blot and indirect immunofluorescence assay. The effects of nsp1 on the induction of typeⅠinterferon were evaluated by dual luciferase reporter gene assay, ELISA and VSV bioassay...
August 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28852929/n-pro-his49-and-e-rns-lys412-mutations-in-pig-bovine-viral-diarrhea-virus-type-2-synergistically-enhance-the-cellular-antiviral-response
#8
Jie Tao, Benqiang Li, Jinghua Chen, Chunling Zhang, Yufei Ma, Guoqiang Zhu, Huili Liu
Type I interferons are major components of the innate immune response of hosts, and accordingly, many viruses have evolved mechanisms to modulate the host response during infection. Bovine viral diarrhea virus (BVDV) nonstructural protein N(pro) and structural protein E(rns) play important roles in inhibiting type I interferon. The aim of this study was to explore the epistatic effects of amino acid mutations in N(pro) and E(rns) in porcine ST cells to characterize the immune response induced by BVDV-2. Plasmids with mutant amino acids His49 (H49), Glu22 (E22) in N(pro), and His300 (H300), Lys412 (K412) in E(rns) which had been changed to Alanine (A) had similar effects on type I interferon production in MDBK and ST cells, but resulted in much greater ISG15, OAS, and Mx production in ST cells...
August 29, 2017: Virus Genes
https://www.readbyqxmd.com/read/28852124/oxidative-stress-and-immune-responses-during-hepatitis-c-virus-infection-in-tupaia-belangeri
#9
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Takahiro Sanada, Haiying Chi, Yukiko Hayashi, Khadija Rebbani, Bouchra Kitab, Aya Matsuu, Noriaki Miyoshi, Tsunekazu Hishima, Michinori Kohara, Kyoko Tsukiyama-Kohara
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. To address the molecular basis of HCV pathogenesis using tupaias (Tupaia belangeri), we characterized host responses upon HCV infection. Adult tupaias were infected with HCV genotypes 1a, 1b, 2a, or 4a. Viral RNA, alanine aminotransferase, anti-HCV core and anti-nonstructural protein NS3 antibody titres, reactive oxygen species (ROS), and anti-3β-hydroxysterol-Δ24reductase (DHCR24) antibody levels were measured at 2-week intervals from 0 to 41 weeks postinfection...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851847/rotavirus-nsp1-requires-casein-kinase-ii-mediated-phosphorylation-for-hijacking-of-cullin-ring-ligases
#10
Kaitlin A Davis, Marco Morelli, John T Patton
The rotavirus nonstructural protein NSP1 repurposes cullin-RING E3 ubiquitin ligases (CRLs) to antagonize innate immune responses. By functioning as substrate adaptors of hijacked CRLs, NSP1 causes ubiquitination and proteasomal degradation of host proteins that are essential for expression of interferon (IFN) and IFN-stimulated gene products. The target of most human and porcine rotaviruses is the β-transducin repeat-containing protein (β-TrCP), a regulator of NF-κB activation. β-TrCP recognizes a phosphorylated degron (DSGΦXS) present in the inhibitor of NF-κB (IκB); phosphorylation of the IκB degron is mediated by IκB kinase (IKK)...
August 29, 2017: MBio
https://www.readbyqxmd.com/read/28835495/the-uncoupling-of-protease-trans-cleavage-and-helicase-activities-in-the-pestivirus-ns3
#11
Fengwei Zheng, Guoliang Lu, Ling Li, Peng Gong, Zishu Pan
The nonstructural protein NS3 from the Flaviviridae family is a multi-functional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the Classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at 2.35 Å resolution. The structure reveals a previously unidentified ∼2200-Å(2) intra-molecular protease-helicase interface comprising three clusters of interactions, representing a "closed" global conformation related to the NS3-NS4A cis-cleavage event...
August 23, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28833932/nonstructural-protein-5a-ns5a-resistance-profile-in-patients-with-chronic-hepatitis-c-treated-with-ledipasvir-containing-regimens-without-sofosbuvir
#12
Kathryn M Kitrinos, Amoreena C Corsa, Angela Worth, Charlotte Hedskog, Diana Brainard, Michael D Miller, Hongmei Mo
The study aimed to evaluate the effects of baseline hepatitis C virus (HCV) NS5A resistance-associated substitutions (RASs) on sustained virologic response to ledipasvir (LDV)-containing regimens in the absence of sofosbuvir (SOF) in patients with HCV genotype (GT) 1 infection across 6 phase 2 clinical studies. We analyzed data from 1103 patients who received either LDV+vedroprevir (NS3 PI)+tegobuvir (NS5B inhibitor)±ribavirin or LDV+ribavirin+pegylated interferon. Population sequencing of HCV NS5A was performed at baseline and at virologic failure from patient plasma samples...
August 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28820725/understanding-hepatitis-c-virus-drug-resistance-clinical-implications-for-current-and-future-regimens
#13
David L Wyles, Anne F Luetkemeyer
Viral resistance to direct-acting antiviral drugs may impact their effectiveness during treatment of hepatitis C virus (HCV) infection. Most data on HCV drug resistance concern genotypes 1 and 3. The clinical impact of resistance to HCV nonstructural protein 5A (NS5A) inhibitors and a practical approach to indications and methods for resistance testing are discussed.
July 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28815532/hepatitis-c-virus-replication
#14
Tetsuro Suzuki
Viruses use synthetic mechanism and organelles of the host cells to facilitate their replication and make new viruses. Host's ATP provides necessary energy. Hepatitis C virus (HCV) is a major cause of liver disease. Like other positive-strand RNA viruses, the HCV genome is thought to be synthesized by the replication complex, which consists of viral- and host cell-derived factors, in tight association with structurally rearranged vesicle-like cytoplasmic membranes. The virus-induced remodeling of subcellular membranes, which protect the viral RNA from nucleases in the cytoplasm, promotes efficient replication of HCV genome...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28809743/outcomes-for-cirrhotic-patients-with-hepatitis-c-virus-1b-treated-with-asunaprevir-and-daclatasvir-combination
#15
Akihiro Tamori, Hoang Hai, Sawako Uchida-Kobayashi, Masaru Enomoto, Ritsuzo Kozuka, Hiroyuki Motoyama, Etsushi Kawamura, Atsushi Hagihara, Yuga Teranishi, Kanako Yoshida, Hiroyasu Morikawa, Yoshiki Murakami, Norifumi Kawada
BACKGROUND: The efficacy and safety of asunaprevir + daclatasvir combination therapy for treatment of hepatitis C virus (HCV) in compensated cirrhotic patients was not fully evaluated in real-world. Outcomes were assessed in cirrhotic patients with sustained viral response (SVR). MATERIAL AND METHODS: A total of 145 patients without resistance-associated substitutions (RASs) at L31 and Y93 in the nonstructural protein 5A of HCV genotype 1b, consisting of 49 hepatic cirrhotic and 96 non-cirrhotic patients, were enrolled to the therapy...
September 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28806616/parvovirus-b19-integration-into-human-cd36-erythroid-progenitor-cells
#16
Tyler Janovitz, Susan Wong, Neal S Young, Thiago Oliveira, Erik Falck-Pedersen
The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome...
August 11, 2017: Virology
https://www.readbyqxmd.com/read/28771475/evolution-and-spread-of-venezuelan-equine-encephalitis-complex-alphavirus-in-the-americas
#17
Naomi L Forrester, Joel O Wertheim, Vivian G Dugan, Albert J Auguste, David Lin, A Paige Adams, Rubing Chen, Rodion Gorchakov, Grace Leal, Jose G Estrada-Franco, Jyotsna Pandya, Rebecca A Halpin, Kumar Hari, Ravi Jain, Timothy B Stockwell, Suman R Das, David E Wentworth, Martin D Smith, Sergei L Kosakovsky Pond, Scott C Weaver
Venezuelan equine encephalitis (VEE) complex alphaviruses are important re-emerging arboviruses that cause life-threatening disease in equids during epizootics as well as spillover human infections. We conducted a comprehensive analysis of VEE complex alphaviruses by sequencing the genomes of 94 strains and performing phylogenetic analyses of 130 isolates using complete open reading frames for the nonstructural and structural polyproteins. Our analyses confirmed purifying selection as a major mechanism influencing the evolution of these viruses as well as a confounding factor in molecular clock dating of ancestors...
August 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28765561/antibodies-against-modified-ns1-wing-domain-peptide-protect-against-dengue-virus-infection
#18
Yen-Chung Lai, Yung-Chun Chuang, Ching-Chuan Liu, Tzong-Shiann Ho, Yee-Shin Lin, Robert Anderson, Trai-Ming Yeh
Dengue is the most common mosquito-transmitted viral infection for which an improved vaccine is still needed. Although nonstructural protein-1 (NS1) immunization can protect mice against dengue infection, molecular mimicry between NS1 and host proteins makes NS1-based vaccines challenging to develop. Based on the epitope recognized by the anti-NS1 monoclonal Ab (mAb) 33D2 which recognizes a conserved NS1 wing domain (NS1-WD) region but not host proteins, we synthesized a modified NS1-WD peptide to immunize mice...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759334/b-cell-tetramer-development-for-veterinary-vaccinology
#19
Michael C Rahe, Kevin L Gustafson, Michael P Murtaugh
Immunological memory is elicited after either vaccination or natural exposure to a pathogen and is essential for protection against re-exposure. Despite its critical importance, the ability to interrogate the veterinary animal memory immune response has long been hindered by a paucity of tools to assess immunological memory. As a result, the evaluation and analysis of protective immune responses that predict immune protection in food and fiber animals and facilitate vaccine development are obstructed. To fill this gap in knowledge in swine, we created a B cell tetramer to porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 7 (nsp7) to efficiently and effectively investigate the memory B cell response, a hallmark of anti-viral immunity...
July 31, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28758632/tree-shrew-a-potential-animal-model-for-hepatitis-c-supports-the-infection-and-replication-of-hcv-in-vitro-and-in-vivo
#20
Yue Feng, Yue-Mei Feng, Caixia Lu, Yuanyuan Han, Li Liu, Xiaomei Sun, Jiejie Dai, Xueshan Xia
The tree shrew (Tupaia belangeri chinensis), a small animal widely distributed in Southeast Asia and southwest China, has the potential to be developed as an animal model for hepatitis C. To determine the susceptibility of the tree shrew to hepatitis C virus (HCV) infection in vitro and in vivo, a well-established HCV, produced from the J6/JFH1-Huh7.5.1 culture system, was used to infect cultured primary tupaia hepatocytes (PTHs) and tree shrews. The in vitro results showed that HCV genomic RNA and HCV-specific nonstructural protein 5A (NS5A) could be detected in the PTH cell culture from days 3-15 post-infection, although the viral load was lower than that observed in Huh7...
August 2017: Journal of General Virology
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