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viral nonstructural protein

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https://www.readbyqxmd.com/read/29769334/reovirus-nonstructural-protein-%C3%AF-ns-acts-as-an-rna-stability-factor-promoting-viral-genome-replication
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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/29719060/phylogenetic-analysis-of-human-g9p-8-rotavirus-strains-circulating-in-jiangsu-china-between-2010-and-2016
#7
Cheng Xu, Jianguang Fu, Jing Ai, Jun Zhang, Cheng Liu, Xiang Huo, Changjun Bao, Yefei Zhu
Rotavirus A (RVA) is the leading cause of acute viral gastroenteritis in children under 5 years of age worldwide. G9P[8] is a common RVA genotype that has been persistently prevalent in Jiangsu, China. To determine the genetic diversity of G9P[8] RVAs, seven representative G9P[8] strains collected from Suzhou Children's Hospital between 2010 and 2016 (named JS2010-JS2016) were analyzed through whole-genome sequencing. All evaluated strains showed the Wa-like constellation G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1...
May 2, 2018: Journal of Medical Virology
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
#8
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
#9
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/29673347/structure-activity-relationship-sar-and-quantitative-structure-activity-relationship-qsar-studies-showed-plant-flavonoids-as-potential-inhibitors-of-dengue-ns2b-ns3-protease
#10
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/29588492/sfts-phlebovirus-promotes-lc3-ii-accumulation-and-nonstructural-protein-of-sfts-phlebovirus-co-localizes-with-autophagy-proteins
#11
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/29563291/a-naturally-occurring-deletion-in-the-effector-domain-of-h5n1-swine-influenza-virus-nonstructural-protein-1-regulates-viral-fitness-and-host-innate-immunity
#12
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
https://www.readbyqxmd.com/read/29563287/nonstructural-5a-impairs-dna-damage-repair-implication-of-hepatitis-c-virus-mediated-hepatocarcinogenesis
#13
Tram T Nguyen, Eun-Mee Park, Yun-Sook Lim, Soon B Hwang
RAD51-associated protein 1 (RAD51AP1) is a member of the multiprotein complexes postulated to carry out RAD51-mediated homologous recombination and DNA repair in mammalian cells. In the present study, we showed that hepatitis C virus (HCV) NS5A directly bound RAD51AP1 and increased protein level of RAD51AP1 through modulation of the ubiquitin-proteasome pathway. We also demonstrated that RAD51AP1 protein levels were increased in the liver tissues of HCV-infected patients and NS5A transgenic mice. Importantly, NS5A impaired DNA repair by disrupting RAD51/RAD51AP1/UAF1 complex and rendered HCV-infected cells more sensitive to DNA damage...
March 21, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29558158/interactome-analysis-of-ns1-protein-encoded-by-influenza-a-h7n9-virus-reveals-an-inhibitory-role-of-ns1-in-host-mrna-maturation
#14
Rei-Lin Kuo, Chi-Jene Chen, Ee-Hong Tam, Chung-Guei Huang, Li-Hsin Li, Zong-Hua Li, Pei-Chia Su, Hao-Ping Liu, Chih-Ching Wu
Influenza A virus infections can result in severe respiratory diseases. The H7N9 subtype of avian influenza A virus has been transmitted to humans and caused severe disease and death. Nonstructural protein 1 (NS1) of influenza A virus is a virulence determinant during viral infection. To elucidate the functions of the NS1 encoded by influenza A H7N9 virus (H7N9 NS1), interaction partners of H7N9 NS1 in human cells were identified with immunoprecipitation followed by SDS-PAGE coupled with liquid chromatography-tandem mass spectrometry (GeLC-MS/MS)...
March 20, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29557328/dengue-fever-as-an-emerging-infection-in-southeast-iran
#15
Mostafa Heydari, Maliheh Metanat, Mohammad-Ali Rouzbeh-Far, Seyed Mehdi Tabatabaei, Mohammad Rakhshani, Nahid Sepehri-Rad, Maryam Keshtkar-Jahromi
Dengue fever (DF) is a mosquito-borne acute viral disease presenting with hemorrhagic manifestations in severe cases. Southeast Iran is in close proximity to Pakistan, an endemic country for DF. This cross-sectional study was conducted in the Sistan and Baluchestan province in the southeast of Iran to investigate possibility of DF (immunoglobulin M [IgM], immunoglobulin G [IgG], and nonstructural protein 1 [NS1] antigen tests) in 60 clinically suspected patients (April 2013 to August 2015). NS1 protein was detected in 5% ( N = 3), at least one of the antibodies (IgM and/ or IgG) was detected in 11% ( N = 7) of the samples...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29548803/molecular-typing-of-a-novel-canine-parvovirus-type-2a-mutant-circulating-in-italy
#16
Francesco Mira, Giulia Dowgier, Giuseppa Purpari, Domenico Vicari, Santina Di Bella, Giusi Macaluso, Francesca Gucciardi, Vincenzo Randazzo, Nicola Decaro, Annalisa Guercio
Canine parvovirus (CPV) is the etiological agent of a severe viral disease of dogs. After its emergence in late 1970s, the CPV original type (CPV-2) was rapidly and totally replaced by three antigenic variants named CPV-2a, CPV-2b and CPV-2c. CPV has an evolutionary rate nearest to those of RNA viruses, with consequences on disease diagnosis and epidemiology. This paper reports the molecular characterization of eight CPV-2a strains collected from dogs in Italy in 2016-2017. Genetic analysis was conducted on a CPV genomic region encompassing both open reading frames (ORFs) encoding for nonstructural (NS1-NS2) and structural proteins (VP1-VP2)...
March 13, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29535204/interactions-between-the-hepatitis-c-virus-nonstructural-2-protein-and-host-adaptor-proteins-1-and-4-orchestrate-virus-release
#17
Fei Xiao, Stanley Wang, Rina Barouch-Bentov, Gregory Neveu, Szuyuan Pu, Melanie Beer, Stanford Schor, Sathish Kumar, Vlad Nicolaescu, Brett D Lindenbach, Glenn Randall, Shirit Einav
Hepatitis C virus (HCV) spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs) AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting. We reported that AP-1A mediates HCV trafficking during release, whereas the endocytic adaptor AP-2 mediates entry and assembly...
March 13, 2018: MBio
https://www.readbyqxmd.com/read/29525670/cellular-hsp27-interacts-with-classical-swine-fever-virus-ns5a-protein-and-negatively-regulates-viral-replication-by-the-nf-%C3%AE%C2%BAb-signaling-pathway
#18
Shifeng Ling, Mingyang Luo, Shengnan Jiang, Jiayu Liu, Chunying Ding, Qinghuan Zhang, Huancheng Guo, Wenjie Gong, Changchun Tu, Jinfu Sun
Classical swine fever virus (CSFV) nonstructural protein NS5A is a multifunctional protein functioning in regulation of viral genome replication, protein translation and assembly by interaction with viral or host proteins. Here, heat shock protein 27 (Hsp27) has been identified as a novel binding partner of NS5A by using His tag "pull down" coupled with shotgun LC-MS/MS, with interaction of both proteins further confirmed by co-immunoprecipitation and laser confocal assays. In PK-15 cells, silencing of Hsp27 expression by siRNA enhanced CSFV replication, and upregulation of Hsp27 inhibited viral proliferation...
March 8, 2018: Virology
https://www.readbyqxmd.com/read/29523827/hsp90-interacts-with-multiple-dengue-virus-2-proteins
#19
Kanjana Srisutthisamphan, Krit Jirakanwisal, Suwipa Ramphan, Natthida Tongluan, Atichat Kuadkitkan, Duncan R Smith
Infections with the mosquito-borne dengue virus (DENV) remain a significant public health challenge. In the absence of a commercial therapeutic to treat DENV infection, a greater understanding of the processes of cellular replication is required. The abundant cellular chaperone protein heat shock protein 90 (Hsp90) has been shown to play a proviral role in the replication cycle of several viruses, predominantly through the stabilization of specific viral proteins. To investigate any potential role of Hsp90 in DENV infection the interaction between Hsp90 and DENV proteins was determined through co-immunoprecipitation experiments...
March 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29518228/the-nlrp3-inflammasome-activation-mediates-zika-virus-associated-inflammation
#20
Zhenjian He, Jiahui Chen, Shu An, Xinhuai Dong, Jianchen Yu, Shihao Zhang, Yun Wu, Ge Li, Yu Zhang, Jueheng Wu, Xun Zhu, Mengfeng Li
Zika virus (ZIKV) is a mosquito-borne virus that has been identified as a cause of several severe disease manifestations, including congenital microcephaly and Guillain-Barré syndrome, meningoencephalitis and myelitis. Previous studies showed that ZIKV-infected patients exhibited elevated plasma levels of interleukin-1β (IL-1β), indicating that ZIKV may activate inflammasomes. However, the molecular basis for its viral pathogenesis remains poorly understood. In this current study, we found that ZIKV infection caused severe inflammatory pathological changes and promoted IL-1β production in vitro as well as in vivo...
March 6, 2018: Journal of Infectious Diseases
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