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Flavivirus NS3

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https://www.readbyqxmd.com/read/27903271/differential-humoral-and-cellular-immunity-induced-by-vaccination-using-plasmid-dna-and-protein-recombinant-expressing-the-ns3-protein-of-dengue-virus-type-3
#1
M L Hurtado-Melgoza, A Ramos-Ligonio, L M Álvarez-Rodríguez, T Meza-Menchaca, A López-Monteon
BACKGROUND: The dengue non-structural 3 (NS3) is a multifunctional protein, containing a serine-protease domain, located at the N-terminal portion, and helicase, NTPase and RTPase domains present in the C-terminal region. This protein is considered the main target for CD4+ and CD8+ T cell responses during dengue infection, which may be involved in protection. However, few studies have been undertaken evaluating the use of this protein as a protective antigen against dengue, as well as other flavivirus...
December 1, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27845325/structure-of-the-ns2b-ns3-protease-from-zika-virus-after-self-cleavage
#2
Wint Wint Phoo, Yan Li, Zhenzhen Zhang, Michelle Yueqi Lee, Ying Ru Loh, Yaw Bia Tan, Elizabeth Yihui Ng, Julien Lescar, CongBao Kang, Dahai Luo
The recent outbreak of Zika virus (ZIKV) infections in the Americas represents a serious threat to the global public health. The viral protease that processes viral polyproteins during infection appears as an attractive drug target. Here we report a crystal structure at 1.84 Å resolution of ZIKV non-structural protein NS2B-NS3 protease with the last four amino acids of the NS2B cofactor bound at the NS3 active site. This structure represents a post-proteolysis state of the enzyme during viral polyprotein processing and provides insights into peptide substrate recognition by the protease...
November 15, 2016: Nature Communications
https://www.readbyqxmd.com/read/27805221/analysis-of-worldwide-sequence-mutations-in-zika-virus-proteins-e-ns1-ns3-and-ns5-from-a-structural-point-of-view
#3
C F Baez, V A Barel, A M T de Souza, C R Rodrigues, R B Varella, N Cirauqui
Zika virus (ZIKV) is an emergent arbovirus that has attracted attention in the last year as a possible causative agent of congenital malformation; it shows a remarkably increased microcephaly risk during otherwise healthy pregnancies. We present here an analysis of all ZIKV sequences available in Genbank up to April 2016, studying the mutations in the whole polyprotein and their possible structural implications for the proteins E, NS1, NS3 and NS5. This study suggests that microcephaly is not a consequence of any particular amino acid substitution but, conceivably, is a feature of ZIKV itself...
November 2, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27763656/cd4-and-cd8-t-cell-immunity-to-dengue-lessons-for-the-study-of-zika-virus
#4
Laura Rivino, Mei Qiu Lim
Dengue (DENV) and Zika viruses (ZIKV) are rapidly emerging mosquito-borne flaviviruses which represent a public health concern. Understanding host protective immunity to these viruses is critical for the design of optimal vaccines. Over a decade of research has highlighted a significant contribution of the T cell response to both protection and/or disease enhancement during dengue infection, the latter being mainly associated with sub-optimal cross-reactive T cell responses during secondary infections. Phase IIb/III clinical trials of the first licensed tetravalent dengue vaccine highlight increased vaccine efficacy in dengue-immune as opposed to dengue-naïve vaccinees, suggesting a possible immunoprotective role of pre-existing DENV-specific T cells that are boosted upon vaccination...
October 20, 2016: Immunology
https://www.readbyqxmd.com/read/27679979/structure-based-discovery-of-two-antiviral-inhibitors-targeting-the-ns3-helicase-of-japanese-encephalitis-virus
#5
Jin'e Fang, Huan Li, Dexin Kong, Shengbo Cao, Guiqing Peng, Rui Zhou, Huanchun Chen, Yunfeng Song
Japanese encephalitis virus (JEV) is a flavivirus that threatens more than half of the world's population. Vaccination can prevent the disease, but no specific antiviral drug is yet available for clinical therapy, and the death rate caused by JEV can reach as high as 60%. The C-terminus of non-structural protein 3 (NS3) of flavivirus encodes helicase and has been identified as a potential drug target. In this study, high throughput molecular docking was employed to identify candidate JEV NS3 helicase inhibitors in a commercial library containing 250,000 compounds...
September 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27670692/phylogenesys-and-homology-modeling-in-zika-virus-epidemic-food-for-thought
#6
Silvia Angeletti, Alessandra Lo Presti, Marta Giovanetti, Alba Grifoni, Massimo Amicosante, Marco Ciotti, Luiz-Carlos J Alcantara, Eleonora Cella, Massimo Ciccozzi
Zika virus (ZIKV) is an emerging Flavivirus that have recently caused an outbreak in Brazil and rapid spread in several countries. In this study, the consequences of ZIKV evolution on protein recognition by the host immune system have been analyzed. Evolutionary analysis was combined with homology modeling and T-B cells epitope predictions. Two separate clades, the African one with the Uganda sequence, as the most probable ancestor, and the second one containing all the most recent sequences from the equatorial belt were identified...
September 27, 2016: Pathogens and Global Health
https://www.readbyqxmd.com/read/27593564/the-ns3-and-ns4a-genes-as-the-targets-of-rna-interference-inhibit-replication-of-japanese-encephalitis-virus-in-vitro-and-in-vivo
#7
Lei Yuan, Rui Wu, Hanyang Liu, Xintian Wen, Xiaobo Huang, Yiping Wen, Xiaoping Ma, Qigui Yan, Yong Huang, Qin Zhao, Sanjie Cao
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that can cause acute encephalitis with a high fatality rate. RNA interference (RNAi) is a powerful tool to silence gene expression and a potential therapy for virus infection. In this study, the antiviral ability of eight shRNA expression plasmids targeting different sites of the NS3 and NS4A genes of JEV was determined in BHK21 cells and mice. The pGP-NS3-3 and pGP-NS4A-4 suppressed 93.9% and 82.0% of JEV mRNA in cells, respectively. The virus titer in cells was reduced approximately 950-fold by pretreating with pGP-NS3-4, and 640-fold by pretreating with pGP-NS4A-4...
December 15, 2016: Gene
https://www.readbyqxmd.com/read/27548676/utilisation-of-isa-reverse-genetics-and-large-scale-random-codon-re-encoding-to-produce-attenuated-strains-of-tick-borne-encephalitis-virus-within-days
#8
Lauriane de Fabritus, Antoine Nougairède, Fabien Aubry, Ernest A Gould, Xavier de Lamballerie
Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27384651/infection-of-common-marmosets-with-gb-virus-b-chimeric-virus-encoding-the-major-nonstructural-proteins-ns2-to-ns4a-of-hepatitis-c-virus
#9
Shaomei Zhu, Tingting Li, Bochao Liu, Yuxia Xu, Yachun Sun, Yilin Wang, Yuanzhan Wang, Lifang Shuai, Zixuan Chen, Jean-Pierre Allain, Chengyao Li
UNLABELLED: A lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis C virus (HCV) vaccines and affordable antiviral drugs. In this study, HCV/GB virus B (GBV-B) chimeric virus carrying the major nonstructural proteins NS2 to NS4A (HCV NS2 to -4A chimera) was produced and used to infect common marmosets, since HCV NS2 to NS4A proteins are critical proteases and major antigens. Seven marmosets were inoculated intrahepatically with HCV NS2 to -4A chimera RNA for primary infection or intravenously injected with chimera-containing serum for passage infection...
September 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27296393/predicting-zika-virus-structural-biology-challenges-and-opportunities-for-intervention
#10
Bryan D Cox, Richard A Stanton, Raymond F Schinazi
BACKGROUND: Zika virus is an emerging crisis as infection is implicated in severe neurological disorders-Guillain-Barré syndrome and fetal microcephaly. There are currently no treatment options available for Zika virus infection. This virus is part of the flavivirus genus and closely related to Dengue Fever Virus, West Nile Virus, and Japanese Encephalitis Virus. Like other flaviviruses, the Zika virus genome encodes three structural proteins (capsid, precursor membrane, and envelope) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5)...
August 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/27198866/insect-specific-flaviviruses-in-aedes-mosquitoes-in-greece
#11
Anna Papa, Elpida Papadopoulou, Ravish Paliwal, Stella Kalaitzopoulou, Spiros Mourelatos, Matthias Niedrig
Mosquitoes of the genus Aedes are known vectors of pathogenic flaviviruses, and insect-specific flaviviruses (ISFs) have been detected in members of this genus in numerous parts of the world. In order to gain insight into whether Aedes mosquitoes in Greece are infected by flaviviruses, 1173 Aedes spp. mosquitoes collected in 2010 and 2012 were grouped in 53 pools and tested by RT nested PCR using flavivirus generic primers. Eight pools (15.09 %) were found to be PCR positive: five pools (5/53, 9.4 %) contained RNA sequences related to Ochlerotatus caspius flavivirus (OCFV), an ISF previously detected in the Iberian peninsula, two pools (2/53, 3...
August 2016: Archives of Virology
https://www.readbyqxmd.com/read/27169727/population-genomics-of-dengue-virus-serotype-4-insights-into-genetic-structure-and-evolution
#12
Vaishali P Waman, Sunitha Manjari Kasibhatla, Mohan M Kale, Urmila Kulkarni-Kale
The spread of dengue disease has become a global public health concern. Dengue is caused by dengue virus, which is a mosquito-borne arbovirus of the genus Flavivirus, family Flaviviridae. There are four dengue virus serotypes (1-4), each of which is known to trigger mild to severe disease. Dengue virus serotype 4 (DENV-4) has four genotypes and is increasingly being reported to be re-emerging in various parts of the world. Therefore, the population structure and factors shaping the evolution of DENV-4 strains across the world were studied using genome-based population genetic, phylogenetic and selection pressure analysis methods...
August 2016: Archives of Virology
https://www.readbyqxmd.com/read/27053551/transmembrane-domains-of-ns2b-contribute-to-both-viral-rna-replication-and-particle-formation-in-japanese-encephalitis-virus
#13
Xiao-Dan Li, Cheng-Lin Deng, Han-Qing Ye, Hong-Lei Zhang, Qiu-Yan Zhang, Dong-Dong Chen, Pan-Tao Zhang, Pei-Yong Shi, Zhi-Ming Yuan, Bo Zhang
UNLABELLED: Flavivirus nonstructural protein 2B (NS2B) is a transmembrane protein that functions as a cofactor for viral NS3 protease. The cytoplasmic region (amino acids 51 to 95) alone of NS2B is sufficient for NS3 protease activity, whereas the role of transmembrane domains (TMDs) remains obscure. Here, we demonstrate for the first time that flavivirus NS2B plays a critical role in virion assembly. Using Japanese encephalitis virus (JEV) as a model, we performed a systematic mutagenesis at the flavivirus conserved residues within the TMDs of NS2B...
June 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27038827/detection-and-sequencing-of-west-nile-virus-rna-from-human-urine-and-serum-samples-during-the-2014-seasonal-period
#14
Anna Nagy, Enikő Bán, Orsolya Nagy, Emőke Ferenczi, Ágnes Farkas, Krisztián Bányai, Szilvia Farkas, Mária Takács
West Nile virus, a widely distributed mosquito-borne flavivirus, is responsible for numerous animal and human infections in Europe, Africa and the Americas. In Hungary, the average number of human infections falls between 10 and 20 cases each year. The severity of clinically manifesting infections varies widely from the milder form of West Nile fever to West Nile neuroinvasive disease (WNND). In routine laboratory diagnosis of human West Nile virus infections, serological methods are mainly applied due to the limited duration of viremia...
July 2016: Archives of Virology
https://www.readbyqxmd.com/read/27009958/a-proline-rich-n-terminal-region-of-the-dengue-virus-ns3-is-crucial-for-infectious-particle-production
#15
Leopoldo G Gebhard, Néstor G Iglesias, Laura A Byk, Claudia V Filomatori, Federico A De Maio, Andrea V Gamarnik
UNLABELLED: Dengue virus is currently the most important insect-borne viral human pathogen. Viral nonstructural protein 3 (NS3) is a key component of the viral replication machinery that performs multiple functions during viral replication and participates in antiviral evasion. Using dengue virus infectious clones and reporter systems to dissect each step of the viral life cycle, we examined the requirements of different domains of NS3 on viral particle assembly. A thorough site-directed mutagenesis study based on solvent-accessible surface areas of NS3 revealed that, in addition to being essential for RNA replication, different domains of dengue virus NS3 are critically required for production of infectious viral particles...
June 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/26864387/an-updated-evolutionary-study-of-flaviviridae-ns3-helicase-and-ns5-rna-dependent-rna-polymerase-reveals-novel-invariable-motifs-as-potential-pharmacological-targets
#16
Louis Papageorgiou, Styliani Loukatou, Kossida Sofia, Dimitrios Maroulis, Dimitrios Vlachakis
The rate of Flaviviridae family virus infections worldwide has increased dramatically in the last few years. In addition, infections caused by arthropod vector viruses including Hepatitis C, West Nile, Dengue fever, Yellow fever and Japanese encephalitis are emerging throughout the world. Based on a recent taxon update, the Flaviviridae family comprises four main genera; Flavivirus, Hepacivirus, Pestivirus and a recent genus Pegivirus. Although the new scientific classification plays a key role in providing useful information about the relationships between viruses, many new documented viruses remain unclassified...
June 21, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/26819305/microrna-33a-5p-modulates-japanese-encephalitis-virus-replication-by-targeting-eukaryotic-translation-elongation-factor-1a1
#17
Zheng Chen, Jing Ye, Usama Ashraf, Yunchuan Li, Siqi Wei, Shengfeng Wan, Ali Zohaib, Yunfeng Song, Huanchun Chen, Shengbo Cao
UNLABELLED: Japanese encephalitis virus (JEV) is a typical mosquito-borne flavivirus responsible for acute encephalitis and meningitis in humans. However, the molecular mechanism for JEV pathogenesis is still unclear. MicroRNAs (miRNAs) are small noncoding RNAs that act as gene regulators. They are directly or indirectly involved in many cellular functions owing to their ability to target mRNAs for degradation or translational repression. However, how cellular miRNAs are regulated and their functions during JEV infection are largely unknown...
April 2016: Journal of Virology
https://www.readbyqxmd.com/read/26585500/development-of-a-recombinant-chimeric-tetravalent-dengue-vaccine-candidate
#18
REVIEW
Jorge E Osorio, Charalambos D Partidos, Derek Wallace, Dan T Stinchcomb
Dengue is a significant threat to public health worldwide. Currently, there are no licensed vaccines available for dengue. Takeda Vaccines Inc. is developing a live, attenuated tetravalent dengue vaccine candidate (TDV) that consists of an attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the prM and E protein genes of DENV-1, -3 and -4 expressed in the context of the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4, respectively). TDV has been shown to be immunogenic and efficacious in nonclinical animal models...
December 10, 2015: Vaccine
https://www.readbyqxmd.com/read/26491167/divergent-viruses-discovered-in-arthropods-and-vertebrates-revise-the-evolutionary-history-of-the-flaviviridae-and-related-viruses
#19
Mang Shi, Xian-Dan Lin, Nikos Vasilakis, Jun-Hua Tian, Ci-Xiu Li, Liang-Jun Chen, Gillian Eastwood, Xiu-Nian Diao, Ming-Hui Chen, Xiao Chen, Xin-Cheng Qin, Steven G Widen, Thomas G Wood, Robert B Tesh, Jianguo Xu, Edward C Holmes, Yong-Zhen Zhang
UNLABELLED: Viruses of the family Flaviviridae are important pathogens of humans and other animals and are currently classified into four genera. To better understand their diversity, evolutionary history, and genomic flexibility, we used transcriptome sequencing (RNA-seq) to search for the viruses related to the Flaviviridae in a range of potential invertebrate and vertebrate hosts. Accordingly, we recovered the full genomes of five segmented jingmenviruses and 12 distant relatives of the known Flaviviridae ("flavi-like" viruses) from a range of arthropod species...
October 21, 2015: Journal of Virology
https://www.readbyqxmd.com/read/26367391/phenylalanine-and-phenylglycine-analogues-as-arginine-mimetics-in-dengue-protease-inhibitors
#20
Lena F Weigel, Christoph Nitsche, Dominik Graf, Ralf Bartenschlager, Christian D Klein
Dengue virus is an increasingly global pathogen. One of the promising targets for antiviral drug discovery against dengue and related flaviviruses such as West Nile virus is the viral serine protease NS2B-NS3. We here report the synthesis and in vitro characterization of potent peptidic inhibitors of dengue virus protease that incorporate phenylalanine and phenylglycine derivatives as arginine-mimicking groups with modulated basicity. The most promising compounds were (4-amidino)-L-phenylalanine-containing inhibitors, which reached nanomolar affinities against dengue virus protease...
October 8, 2015: Journal of Medicinal Chemistry
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