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https://www.readbyqxmd.com/read/29792020/daclatasvir-and-asunaprevir-combination-therapy-for-patients-with-chronic-hepatitis-c-virus-genotype-1b-infection-in-real-world
#1
Jae Young Oh, Byung Seok Kim, Chang Hyeong Lee, Jeong Eun Song, Heon Ju Lee, Jung Gil Park, Jae Seok Hwang, Woo Jin Chung, Byoung Kuk Jang, Young Oh Kweon, Won Young Tak, Soo Young Park, Se Young Jang, Jeong Ill Suh, Sang Gyu Kwak
Background/Aims: Previous studies have reported a high rate of sustained virologic response (SVR) and a low rate of serious adverse events with the use of daclatasvir (DCV) and asunaprevir (ASV) combination therapy. We evaluated the efficacy and safety of DCV and ASV combination therapy for patients with chronic hepatitis C virus (HCV) genotype 1b infection in real world. Methods: We enrolled 278 patients (184 treatment-naïve patients) from five hospitals in Daegu and Gyeongsangbuk-do...
May 25, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29782916/identification-of-amino-acid-residues-in-infectious-hematopoietic-necrosis-virus-ihnv-nv-protein-necessary-for-viral-replication-and-pathogenicity
#2
Yang Wu, Li Wang, Tiantian Guo, Yanping Jiang, Xinyuan Qiao, Li Sun, Min Liu, Lijie Tang, Yigang Xu, Yijing Li
Our previous studies demonstrated that the nonstructural NV protein of infectious hematopoietic necrosis virus (IHNV) was essential for efficient viral replication and pathogenicity, and that the amino acid residues 32 EGDL35 of the NV protein were responsible for nuclear localization, and played important roles in suppressing IFN and inhibiting NF-κB activity. However, little is known about the influence of 32 EGDL35 on IHNV replication and pathogenicity. In the present study, two recombinant IHNV strains with deletions of NV 32 EGDL35 were generated and the effect on IHNV replication and pathogenicity was explored...
May 18, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29774829/novel-parvovirus-related-to-primate-bufaviruses-in-dogs
#3
Vito Martella, Gianvito Lanave, Eszter Mihalov-Kovács, Szilvia Marton, Renáta Varga-Kugler, Eszter Kaszab, Barbara Di Martino, Michele Camero, Nicola Decaro, Canio Buonavoglia, Krisztián Bányai
A novel protoparvovirus species, related genetically to human bufaviruses, was identified in dogs with respiratory signs. The canine bufavirus was distantly related to the well-known canine protoparvovirus, canine parvovirus type 2, sharing low amino acid identities in the nonstructural protein 1 (40.6%) and in the capsid protein 1 (33.4%). By screening collections of fecal, nasal, and oropharyngeal samples obtained from juvenile dogs (<1 year of age), canine bufavirus DNA appeared as a common component of canine virome...
June 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29770590/genomic-and-antigenic-characterization-of-porcine-epidemic-diarrhoea-virus-strains-isolated-from-south-korea-2017
#4
Sunhee Lee, Changhee Lee
Porcine epidemic diarrhoea virus (PEDV) is a globally emerging and re-emerging enteric coronavirus in pigs causing serious economic threats to the world swine industry. Since the re-emergence of massive PEDV outbreaks in South Korea in 2013-2014, domestic pig farms have continued to experience PED epidemics or endemics. This study represents the molecular characterization of PEDV isolates identified in diarrhoeic animals collected across the country in 2017. Initial sequencing analysis of the full-length S genes revealed that 70% of the 2017 isolates (7/10) belong to the G2b subgroup, while the remaining isolates were classified as G1b...
May 16, 2018: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29769334/reovirus-nonstructural-protein-%C3%AF-ns-acts-as-an-rna-stability-factor-promoting-viral-genome-replication
#5
Paula F Zamora, Liya Hu, Jonathan J Knowlton, Roni M Lahr, Rodolfo A Moreno, Andrea J Berman, B V Venkataram Prasad, Terence S Dermody
Viral nonstructural proteins, which are not packaged into virions, are essential for replication of most viruses. Reovirus, a nonenveloped, double-stranded RNA (dsRNA) virus, encodes three nonstructural proteins that are required for viral replication and dissemination in the host. Reovirus nonstructural protein σNS is a single-stranded RNA (ssRNA)-binding protein that must be expressed in infected cells for production of viral progeny. However, activities of σNS during individual steps of the reovirus replication cycle are poorly understood...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29760190/tick-borne-encephalitis-virus-nonstructural-protein-ns5-induces-rantes-expression-dependent-on-the-rna-dependent-rna-polymerase-activity
#6
Zifeng Zheng, Jieyu Yang, Xuan Jiang, Yalan Liu, Xiaowei Zhang, Mei Li, Mudan Zhang, Ming Fu, Kai Hu, Hanzhong Wang, Min-Hua Luo, Peng Gong, Qinxue Hu
Tick-borne encephalitis virus (TBEV) is one of the flaviviruses that targets the CNS and causes encephalitis in humans. The mechanism of TBEV that causes CNS destruction remains unclear. It has been reported that RANTES-mediated migration of human blood monocytes and T lymphocytes is specifically induced in the brain of mice infected with TBEV, which causes ensuing neuroinflammation and may contribute to brain destruction. However, the viral components responsible for RANTES induction and the underlying mechanisms remain to be fully addressed...
May 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29743360/orsay-%C3%AE-protein-is-required-for-non-lytic-viral-egress
#7
Wang Yuan, Ying Zhou, Yanlin Fan, Yizhi J Tao, Weiwei Zhong
Non-enveloped gastrointestinal viruses such as human rotavirus can exit infected cells from the apical surface without cell lysis. The mechanism of such non-lytic exit is poorly understood. The non-enveloped Orsay virus is an RNA virus infecting the intestine cells of the nematode Caenorhabditis elegans Dye staining results suggested that Orsay exits from the intestine of infected worms in a non-lytic manner. Therefore, the Orsay- C. elegans system provides an excellent in vivo model to study viral exit. The Orsay genome encodes three proteins: RNA-dependent RNA polymerase, capsid protein (CP), and a nonstructural protein δ...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29742479/flaviviridae-virus-nonstructural-proteins-5-and-5a-mediate-viral-immune-evasion-and-are-promising-targets-in-drug-development
#8
REVIEW
Shun Chen, Chao Yang, Wei Zhang, Suresh Mahalingam, Mingshu Wang, Anchun Cheng
Infections with viruses in the Flaviviridae family have a vast global and economic impact because of the high morbidity and mortality. The pathogenesis of Flaviviridae infections is very complex and not fully understood because these viruses can inhibit multiple immune pathways including the complement system, NK cells, and IFN induction and signalling pathways. The non-structural (NS) 5 and 5A proteins of Flaviviridae viruses are highly conserved and play an important role in resisting host immunity through various evasion mechanisms...
May 6, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29730006/crystal-structure-of-chikungunya-virus-nsp2-cysteine-protease-reveals-a-putative-flexible-loop-blocking-its-active-site
#9
Manju Narwal, Harvijay Singh, Shivendra Pratap, Anjali Malik, Richard J Kuhn, Pravindra Kumar, Shailly Tomar
Chikungunya virus (CHIKV), a mosquito-borne pathogenic alphavirus is a growing public health threat. No vaccines or antiviral drug is currently available in the market for chikungunya treatment. nsP2pro, the viral cysteine protease, carries out an essential function of nonstructural polyprotein processing and forms four nonstructural proteins (nsPs) that makes the replication complex, hence constitute a promising drug target. In this study, crystal structure of nsP2pro has been determined at 2.59 Ǻ, which reveals that the protein consists of two subdomains: N-terminal protease subdomain and C-terminal methyltransferase subdomain...
May 3, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29725417/identification-and-functional-analysis-of-a-core-gene-module-associated-with-hepatitis-c-virus-induced-human-hepatocellular-carcinoma-progression
#10
Gaobo Bai, Wenling Zheng, Wenli Ma
Hepatitis C virus (HCV)-induced human hepatocellular carcinoma (HCC) progression may be due to a complex multi-step processes. The developmental mechanism of these processes is worth investigating for the prevention, diagnosis and therapy of HCC. The aim of the present study was to investigate the molecular mechanism underlying the progression of HCV-induced hepatocarcinogenesis. First, the dynamic gene module, consisting of key genes associated with progression between the normal stage and HCC, was identified using the Weighted Gene Co-expression Network Analysis tool from R language...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29708867/development-of-monoclonal-antibodies-specifically-recognizing-the-nonstructural-protein-12-of-type-2-porcine-reproductive-and-respiratory-syndrome-virus
#11
Liwei Li, Fei Gao, Yifeng Jiang, Wu Tong, Hao Zheng, Tongling Shan, Ning Kong, Hai Yu, Deqiang Yang, Kuan Zhao, Yujiao Zhang, Guangzhi Tong
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important viral pathogens that has caused tremendous economic losses to the swine industry worldwide. Although extensive research has been focused on PRRSV, little is known about the structure and biological functions of individual nonstructural viral proteins, especially the nonstructural protein 12 (Nsp12). In this study, we generated and identified the monoclonal antibody (mAb) against PRRSV Nsp12. Six strains of hybridoma cells named 2B10, 2B12, 5E1, 5G6, 5E7, and 8B2 secreting anti-Nsp12 mAbs were obtained by the hybridoma technique...
April 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29703432/antiviral-activity-safety-and-tolerability-of-multiple-ascending-doses-of-elbasvir-or-grazoprevir-in-participants-infected-with-hepatitis-c-virus-genotype-1-or-3
#12
Wendy W Yeh, Iain P Fraser, Patricia Jumes, Amelia Petry, Inge De Lepeleire, Martine Robberechts, Christina Reitmann, Kristien Van Dyck, Xiaobi Huang, Zifang Guo, Deborah Panebianco, Robert B Nachbar, Edward O'Mara, John A Wagner, Joan R Butterton, Frank J Dutko, Valentin Moiseev, Zhanna Kobalava, Andreas Hüser, Sorin Visan, Christian Schwabe, Edward Gane, Serghei Popa, Nelea Ghicavii, Markus Uhle, Frank Wagner
PURPOSE: Elbasvir (MK-8742) and grazoprevir (MK-5172; Merck & Co, Inc, Kenilworth, New Jersey) are hepatitis C virus (HCV)-specific inhibitors of the nonstructural protein 5A phosphoprotein and the nonstructural protein 3/4A protease, respectively. The aims of these studies were to evaluate the antiviral activity and safety of different doses of elbasvir or grazoprevir each administered as monotherapy to participants infected with either HCV genotype (GT) 1 or GT3. METHODS: These 2 double-blind, randomized, placebo-controlled, sequential-panel, multiple ascending dose studies were conducted to assess the safety and pharmacodynamics of 5 days of once-daily elbasvir or 7 days of once-daily grazoprevir in adult male participants chronically infected with either HCV GT1 or GT3...
April 24, 2018: Clinical Therapeutics
https://www.readbyqxmd.com/read/29702687/macrophage-migration-inhibitory-factor-is-critical-for-dengue-ns1-induced-endothelial-glycocalyx-degradation-and-hyperpermeability
#13
Hong-Ru Chen, Chiao-Hsuan Chao, Ching-Chuan Liu, Tzong-Shiann Ho, Huey-Pin Tsai, Guey-Chuen Perng, Yee-Shin Lin, Jen-Ren Wang, Trai-Ming Yeh
Vascular leakage is one of the salient characteristics of severe dengue. Nonstructural protein 1 (NS1) of dengue virus (DENV) can stimulate endothelial cells to secrete endothelial hyperpermeability factor, macrophage migration inhibitory factor (MIF), and the glycocalyx degradation factor heparanase 1 (HPA-1). However, it is unclear whether MIF is directly involved in NS1-induced glycocalyx degradation. In this study, we observed that among NS1, MIF and glycocalyx degradation-related molecules, the HPA-1, metalloproteinase 9 (MMP-9) and syndecan 1 (CD138) serum levels were all increased in dengue patients, and only NS1 and MIF showed a positive correlation with the CD138 level in severe patients...
April 27, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29673347/structure-activity-relationship-sar-and-quantitative-structure-activity-relationship-qsar-studies-showed-plant-flavonoids-as-potential-inhibitors-of-dengue-ns2b-ns3-protease
#14
Muhammad Waseem Sarwar, Adeel Riaz, Syed Muhammad Raihan Dilshad, Ahmed Al-Qahtani, Muhammad Shah Nawaz-Ul-Rehman, Muhammad Mubin
BACKGROUND: Due to dengue virus disease, half of the world population is at severe health risk. Viral encoded NS2B-NS3 protease complex causes cleavage in the nonstructural region of the viral polyprotein. The cleavage is essentially required for fully functional viral protein. It has already been reported that if function of NS2B-NS3 complex is disrupted, viral replication is inhibited. Therefore, the NS2B-NS3 is a well-characterized target for designing antiviral drug. RESULTS: In this study docking analysis was performed with active site of dengue NS2B-NS3 protein with selected plant flavonoids...
April 19, 2018: BMC Structural Biology
https://www.readbyqxmd.com/read/29661824/development-of-dengue-virus-serotype-specific-ns1-capture-assays-for-the-rapid-and-highly-sensitive-identification-of-the-infecting-serotype-in-human-sera
#15
Katharina Röltgen, Natalie Rose, Alessia Ruggieri, Louisa Warryn, Nicole Scherr, Carlos Augusto Pinho-Nascimento, Marco Tamborrini, Thomas Jaenisch, Gerd Pluschke
Dengue fever can be caused by one of four distinct dengue virus (DENV) serotypes that cocirculate in many parts of the world. Point of care serotype-specific nonstructural protein-1 (NS1) capture assays for the rapid serotyping of DENV in human sera would greatly support epidemiological surveillance and potentially also prognosis in individual patients. To ensure both serotype specificity and broad coverage of variants within serotypes, we have applied an innovative approach for the generation and selection of serotype-specific anti-NS1 mAbs...
April 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29599610/successful-combination-of-direct-antiviral-agents-in-liver-transplanted-patients-with-recurrent-hepatitis-c-virus
#16
Christian Rupp, Theresa Hippchen, Manuel Neuberger, Peter Sauer, Jan Pfeiffenberger, Wolfgang Stremmel, Daniel Nils Gotthardt, Arianeb Mehrabi, Karl-Heinz Weiss
AIM: To analyze the safety and efficiency of direct-acting antiviral (DAA) regimens in liver-transplanted patients with hepatitis C virus (HCV) reinfection. METHODS: Between January 2014 and December 2016, 39 patients with HCV reinfection after liver transplantation were treated at our tertiary referral center with sofosbuvir (SOF)-based regimens, including various combinations with interferon (IFN), daclatasvir (DAC), simeprivir (SIM) and/or ledipasvir (LDV). Thirteen patients were treated with SOF + IFN ± RBV...
March 28, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29590589/molecular-mechanisms-of-tight-binding-through-fuzzy-interactions
#17
Qingliang Shen, Jie Shi, Danyun Zeng, Baoyu Zhao, Pingwei Li, Wonmuk Hwang, Jae-Hyun Cho
Many intrinsically disordered proteins (IDPs) form fuzzy complexes upon binding to their targets. Although many IDPs are weakly bound in fuzzy complexes, some IDPs form high-affinity complexes. One example is the nonstructural protein 1 (NS1) of the 1918 Spanish influenza A virus, which hijacks cellular CRKII through the strong binding affinity (Kd ∼10 nM) of its proline-rich motif (PRMNS1 ) to the N-terminal Src-homology 3 domain of CRKII. However, its molecular mechanism remains elusive. Here, we examine the interplay between structural disorder of a bound PRMNS1 and its long-range electrostatic interactions...
March 27, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29588492/sfts-phlebovirus-promotes-lc3-ii-accumulation-and-nonstructural-protein-of-sfts-phlebovirus-co-localizes-with-autophagy-proteins
#18
Yue Sun, Miao-Miao Liu, Xiao-Ying Lei, Xue-Jie Yu
Autophagy is essential for eukaryotic cell homeostasis and can perform both anti-viral and pro-viral roles depending on the kinds of viruses, cell types and cell environment. Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) is a newly discovered tick-borne virus in the Phenuiviridae family that causes a severe hemorrhagic fever disease in East Asia. In this study we determined interactions between SFTSV and autophagy. Our results showed that LC3-II (microtubule associated protein 1 light chain 3-II) protein accumulated from 4 h to 24 h after SFTSV infection compared to mock-infected Vero cells, and the use of E64d and pepstatin A did not affect the expression of LC3-II protein, which indicated that the increased LC3-II may be the result of inhibition of autophagic degradation caused by SFTSV infection...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29584650/identification-of-a-novel-recombinant-type-2-porcine-reproductive-and-respiratory-syndrome-virus-in-china
#19
Long Zhou, Runmin Kang, Bo Xie, Yiming Tian, Xuan Wu, Xuebin Lv, Xin Yang, Hongning Wang
Since the emergence of NADC30-like porcine reproductive and respiratory syndrome virus (PRRSV) in China in 2013, PRRSVs have undergone rapid evolution. In this study, a novel variant of PRRSV strain (designated SCcd17) was successfully isolated from piglets with clinical signs in Sichuan Province in China in 2017, and the complete genomic sequence was determined. The genome of this new isolate was 15,015 nucleotides (nt) long, and comparative analysis revealed that SCcd17 exhibited 90.2%, 85.2%, 84.9%, and 84...
March 27, 2018: Viruses
https://www.readbyqxmd.com/read/29563291/a-naturally-occurring-deletion-in-the-effector-domain-of-h5n1-swine-influenza-virus-nonstructural-protein-1-regulates-viral-fitness-and-host-innate-immunity
#20
Junyong Wang, Yan Zeng, Shuai Xu, Jiayun Yang, Wanbing Wang, Bo Zhong, Jinying Ge, Lei Yin, Zhigao Bu, Hong-Bing Shu, Hualan Chen, Cao-Qi Lei, Qiyun Zhu
Nonstructural protein 1 (NS1) of influenza A virus regulates innate immune responses via various mechanisms. We previously showed that a naturally occurring deletion (the EALQR motif) in the NS1 effector domain of an H5N1 swine-origin avian influenza virus impairs the inhibition of type I interferon (IFN) in chicken fibroblasts and attenuates virulence in chickens. Here, we found that the virus bearing this deletion in its NS1 effector domain showed diminished inhibition of IFN-related cytokine expression and attenuated virulence in mice...
March 21, 2018: Journal of Virology
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