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https://www.readbyqxmd.com/read/29379028/an-evolutionary-ns1-mutation-enhances-zika-virus-evasion-of-host-interferon-induction
#1
Hongjie Xia, Huanle Luo, Chao Shan, Antonio E Muruato, Bruno T D Nunes, Daniele B A Medeiros, Jing Zou, Xuping Xie, Maria Isabel Giraldo, Pedro F C Vasconcelos, Scott C Weaver, Tian Wang, Ricardo Rajsbaum, Pei-Yong Shi
Virus-host interactions determine an infection outcome. The Asian lineage of Zika virus (ZIKV), responsible for the recent epidemics, has fixed a mutation in the NS1 gene after 2012 that enhances mosquito infection. Here we report that the same mutation confers NS1 to inhibit interferon-β induction. This mutation enables NS1 binding to TBK1 and reduces TBK1 phosphorylation. Engineering the mutation into a pre-epidemic ZIKV strain debilitates the virus for interferon-β induction; reversing the mutation in an epidemic ZIKV strain invigorates the virus for interferon-β induction; these mutational effects are lost in IRF3-knockout cells...
January 29, 2018: Nature Communications
https://www.readbyqxmd.com/read/29321318/viperin-restricts-zika-virus-and-tick-borne-encephalitis-virus-replication-by-targeting-ns3-for-proteasomal-degradation
#2
Christakis Panayiotou, Richard Lindqvist, Chaitanya Kurhade, Kirstin Vonderstein, Jenny Pasto, Karin Edlund, Arunkumar S Upadhyay, Anna K Överby
Flaviviruses are arthropod-borne viruses that constitute a major global health problem, with millions of human infections annually. Their pathogenesis ranges from mild illness to severe manifestations such as hemorrhagic fever and fatal encephalitis. Type I interferons (IFNs) are induced in response to viral infection, and stimulate the expression of interferon-stimulated genes (ISGs), including that encoding viperin (virus-inhibitory protein, endoplasmic reticulum-associated, IFN-inducible), which shows antiviral activity against a broad spectrum of viruses including several flaviviruses...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29147783/new-virus-of-the-family-flaviviridae-detected-in-lumpfish-cyclopterus-lumpus
#3
Renate Hvidsten Skoge, Jarle Brattespe, Arnfinn Lodden Økland, Heidrun Plarre, Are Nylund
In this study, we determined the complete coding sequence of a putative new member of the family Flaviviridae, named "Cyclopterus lumpus virus" (CLuV), which is associated with a serious disease in lumpfish (Cyclopterus lumpus). The virus was present in all tissues tested, but pathology was primarily observed in the liver and kidneys. CLuV shows low but distinct similarity to the unassigned Tamana bat virus (TABV). Unlike other known members of the family Flaviviridae, translation of the entire CLuV polyprotein is dependent on a - 1 ribosomal frameshift in the NS2A region...
November 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29141913/multiplexed-biomarker-panels-discriminate-zika-and-dengue-virus-infection-in-humans
#4
Guang Song, Hee-Sool Rho, Jianbo Pan, Pedro Ramos, Ki-Jun Yoon, Freddy A Medina, Emily M Lee, Daniel J Eichinger, Guo-Li Ming, Jorge L Muñoz-Jordan, Hengli Tang, Ignacio Pino, Hongjun Song, Jiang Qian, Heng Zhu
Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses that cause widespread, acute febrile illnesses, notably microcephaly for fetuses of infected pregnant women. Detecting the viral cause of these illnesses is paramount to determine risks to patients, counsel pregnant women, and help fight outbreaks. A combined diagnostic algorithm for ZIKV and DENV requires Reverse transcription polymerase chain reaction (RT-PCR) and IgM antibody detection. RT-PCR differentiates between DENV and ZIKV infections during the acute phases of infection, but differentiation based on IgM antibodies is currently nearly impossible in endemic areas...
November 15, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29094318/discovery-of-t-cell-driven-subunit-vaccines-from-zika-virus-genome-an-immunoinformatics-approach
#5
Dibyabhaba Pradhan, Monika Yadav, Rashi Verma, Noor Saba Khan, Lingaraja Jena, Arun Kumar Jain
The recent outbreaks of Zika virus and the absence of a specific therapy have necessitated to identify T-cell-stimulating antigenic peptides as potential subunit vaccine candidates. The translated ssRNA (+) genome of Zika virus was explored in EMBOSS antigenic and VaxiJen to predict 63 peptides as potential antigens. Three MHC-II binding peptide prediction tools, viz. NetMHCIIpan, PREDIVAC and immune epitope database (IEDB) were employed in consensus on 63 antigenic peptides to propose 14 T-helper cell epitopes...
November 1, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28991176/innate-immune-evasion-mediated-by-flaviviridae-non-structural-proteins
#6
REVIEW
Shun Chen, Zhen Wu, Mingshu Wang, Anchun Cheng
Flaviviridae-caused diseases are a critical, emerging public health problem worldwide. Flaviviridae infections usually cause severe, acute or chronic diseases, such as liver damage and liver cancer resulting from a hepatitis C virus (HCV) infection and high fever and shock caused by yellow fever. Many researchers worldwide are investigating the mechanisms by which Flaviviridae cause severe diseases. Flaviviridae can interfere with the host's innate immunity to achieve their purpose of proliferation. For instance, dengue virus (DENV) NS2A, NS2B3, NS4A, NS4B and NS5; HCV NS2, NS3, NS3/4A, NS4B and NS5A; and West Nile virus (WNV) NS1 and NS4B proteins are involved in immune evasion...
October 7, 2017: Viruses
https://www.readbyqxmd.com/read/28956770/genome-wide-mutagenesis-of-dengue-virus-reveals-plasticity-of-the-ns1-protein-and-enables-generation-of-infectious-tagged-reporter-viruses
#7
Nicholas S Eyre, Stephen M Johnson, Auda A Eltahla, Maria Aloi, Amanda L Aloia, Christopher A McDevitt, Rowena A Bull, Michael R Beard
Dengue virus (DENV) is a major global pathogen that causes significant morbidity and mortality in tropical and subtropical areas worldwide. An improved understanding of the regions within the DENV genome and its encoded proteins that are required for the virus replication cycle will expedite the development of urgently required therapeutics and vaccines. We subjected an infectious DENV genome to unbiased insertional mutagenesis and used next-generation sequencing to identify sites that tolerate 15-nucleotide insertions during the virus replication cycle in hepatic cell culture...
December 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28919920/virulence-determinants-of-west-nile-virus-how-can-these-be-used-for-vaccine-design
#8
REVIEW
Jaclyn A Kaiser, Tian Wang, Alan Dt Barrett
West Nile virus (WNV), a neurotropic mosquito-borne flavivirus, has become endemic in the USA and parts of Europe since 1999. There is no licensed WNV vaccine for humans. Considering the robust immunity from immunization with live, attenuated vaccines, a live WNV vaccine is an ideal platform for disease control. Animal and mosquito studies have identified a number of candidate attenuating mutations, including the structural proteins premembrane/membrane and envelope, and the nonstructural proteins NS1, NS2A, NS3, NS4A, NS4B and NS5, and the 3' UTR...
May 2017: Future Virology
https://www.readbyqxmd.com/read/28826723/zika-virus-encoded-ns2a-disrupts-mammalian-cortical-neurogenesis-by-degrading-adherens-junction-proteins
#9
Ki-Jun Yoon, Guang Song, Xuyu Qian, Jianbo Pan, Dan Xu, Hee-Sool Rho, Nam-Shik Kim, Christa Habela, Lily Zheng, Fadi Jacob, Feiran Zhang, Emily M Lee, Wei-Kai Huang, Francisca Rojas Ringeling, Caroline Vissers, Cui Li, Ling Yuan, Koeun Kang, Sunghan Kim, Junghoon Yeo, Yichen Cheng, Sheng Liu, Zhexing Wen, Cheng-Feng Qin, Qingfeng Wu, Kimberly M Christian, Hengli Tang, Peng Jin, Zhiheng Xu, Jiang Qian, Heng Zhu, Hongjun Song, Guo-Li Ming
Zika virus (ZIKV) directly infects neural progenitors and impairs their proliferation. How ZIKV interacts with the host molecular machinery to impact neurogenesis in vivo is not well understood. Here, by systematically introducing individual proteins encoded by ZIKV into the embryonic mouse cortex, we show that expression of ZIKV-NS2A, but not Dengue virus (DENV)-NS2A, leads to reduced proliferation and premature differentiation of radial glial cells and aberrant positioning of newborn neurons. Mechanistically, in vitro mapping of protein-interactomes and biochemical analysis suggest interactions between ZIKA-NS2A and multiple adherens junction complex (AJ) components...
September 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28723277/ns2a-comprises-a-putative-viroporin-of-dengue-virus-2
#10
Gaurav Shrivastava, Julio García-Cordero, Moisés León-Juárez, Goldie Oza, Jose Tapia-Ramírez, Nicolas Villegas-Sepulveda, Leticia Cedillo-Barrón
No abstract text is available yet for this article.
July 19, 2017: Virulence
https://www.readbyqxmd.com/read/28720531/molecular-cloning-and-characterization-of-the-genes-encoding-the-proteins-of-zika-virus
#11
Wangheng Hou, Ruth Cruz-Cosme, Najealicka Armstrong, Lilian Akello Obwolo, Fayuan Wen, Wenhui Hu, Min-Hua Luo, Qiyi Tang
Zika virus (ZIKV) encodes a precursor protein (also called polyprotein) of about 3424 amino acids that is processed by proteases to generate 10 mature proteins and a small peptide. In the present study, we characterized the chemical features, suborganelle distribution and potential function of each protein using Flag-tagged protein expression system. Western blot analysis revealed the molecular weight of the proteins and the polymerization of E, NS1, and NS3 proteins. In addition, we performed multi-labeled fluorescent immunocytochemistry and subcellular fractionation to determine the subcellular localization of these proteins in host cells...
September 10, 2017: Gene
https://www.readbyqxmd.com/read/28666739/spontaneous-membrane-insertion-of-a-dengue-virus-ns2a-peptide
#12
Emmanuel Fajardo-Sánchez, Vicente Galiano, José Villalaín
Non-structural NS2A protein of Dengue virus is essential for viral replication but poorly characterized because of its high hydrophobicity. We have previously shown experimentally that NS2A possess a segment, peptide dens25, known to insert into membranes and interact specifically with negatively-charged phospholipids. To characterize its membrane interaction we have used two types of molecular dynamics membrane model systems, a highly mobile membrane mimetic (HMMM) and an endoplasmic reticulum (ER) membrane-like model...
August 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28631054/adaptation-of-tick-borne-encephalitis-virus-from-human-brain-to-different-cell-cultures-induces-multiple-genomic-substitutions
#13
Eugenia P Ponomareva, Vladimir A Ternovoi, Tamara P Mikryukova, Elena V Protopopova, Anastasia V Gladysheva, Alexander N Shvalov, Svetlana N Konovalova, Eugene V Chausov, Valery B Loktev
The C11-13 strain from the Siberian subtype of tick-borne encephalitis virus (TBEV) was isolated from human brain using pig embryo kidney (PEK), 293, and Neuro-2a cells. Analysis of the complete viral genome of the C11-13 variants during six passages in these cells revealed that the cell-adapted C11-13 variants had multiple amino acid substitutions as compared to TBEV from human brain. Seven out of eight amino acids substitutions in the high-replicating C11-13(PEK) variant mapped to non-structural proteins; 13 out of 14 substitutions in the well-replicating C11-13(293) variant, and all four substitutions in the low-replicating C11-13(Neuro-2a) variant were also localized in non-structural proteins, predominantly in the NS2a (2), NS3 (6) and NS5 (3) proteins...
June 19, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28456663/comparative-whole-genome-analysis-of-dengue-virus-serotype-2-strains-differing-in-trans-endothelial-cell-leakage-induction-in-vitro
#14
Sneha Singh, M G Anupriya, Easwaran Sreekumar
The role of genetic differences among dengue virus (DENV) in causing increased microvascular permeability is less explored. In the present study, we compared two closely related DENV serotype-2 strains of Cosmopolitan genotype for their in vitro infectivity phenotype and ability to induce trans-endothelial leakage. We found that these laboratory strains differed significantly in infecting human microvascular endothelial cells (HMEC-1) and hepatocytes (Huh7), two major target cells of DENV in in vivo infections...
April 27, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28441781/dengue-virus-non-structural-protein-5
#15
REVIEW
Abbas El Sahili, Julien Lescar
The World Health Organization estimates that the yearly number of dengue cases averages 390 million. This mosquito-borne virus disease is endemic in over 100 countries and will probably continue spreading, given the observed trend in global warming. So far, there is no antiviral drug available against dengue, but a vaccine has been recently marketed. Dengue virus also serves as a prototype for the study of other pathogenic flaviviruses that are emerging, like West Nile virus and Zika virus. Upon viral entry into the host cell and fusion of the viral lipid membrane with the endosomal membrane, the viral RNA is released and expressed as a polyprotein, that is then matured into three structural and seven non-structural (NS) proteins...
April 24, 2017: Viruses
https://www.readbyqxmd.com/read/28411164/high-levels-of-local-inter-and-intra-host-genetic-variation-of-west-nile-virus-and-evidence-of-fine-scale-evolutionary-pressures
#16
Dylan J Ehrbar, Kiet A Ngo, Scott R Campbell, Laura D Kramer, Alexander T Ciota
West Nile virus (WNV; Flaviviridae, Flavivirus) has been endemic in New York State (NYS) since its 1999 introduction, yet prevalence in Culex mosquitoes varies substantially over small spatial and temporal scales. It is unclear if viral genetics plays a role in this variability, as genetic and phenotypic characterization on local scales has generally been lacking. In addition, intrahost diversity of circulating strains have not been fully characterized despite the documented role of minority variants in viral fitness and virulence...
April 12, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28388487/characterization-of-virus-specific-vesicles-assembled-by-west-nile-virus-non-structural-proteins
#17
Li Yu, Kazuyo Takeda, Yamei Gao
Flavivirus genome encodes seven non-structural proteins (NSPs) and these NSPs are believed to be involved in their genomic RNA replication, of which the mechanism is unclear. We find that West Nile virus (WNV) NSPs were capable of self-assembling membranous vesicles in cells, which are composed of the host endoplasmic reticulum membrane integrated with viral NS1 and NS4A, and possibly NS2A. The vesicles can further organize into replication complex (RC)-associated vesicles which combine both the vesicle and predicted RC components...
June 2017: Virology
https://www.readbyqxmd.com/read/28381578/mutagenesis-of-dengue-virus-protein-ns2a-revealed-a-novel-domain-responsible-for-virus-induced-cytopathic-effect-and-interactions-between-ns2a-and-ns2b-transmembrane-segments
#18
Ren-Huang Wu, Ming-Han Tsai, Kuen-Nan Tsai, Jia Ni Tian, Jian-Sung Wu, Su-Ying Wu, Jyh-Haur Chern, Chun-Hong Chen, Andrew Yueh
The NS2A protein of dengue virus (DENV) has eight predicted transmembrane segments (pTMS1 to -8) and participates in RNA replication, virion assembly, and host antiviral response. However, the roles of specific amino acid residues within the pTMS regions of NS2A during the viral life cycle are not clear. Here, we explore the function of DENV NS2A by introducing a series of alanine substitutions into the N-terminal half (pTMS1 to -4) of the protein in the context of a DENV infectious clone or subgenomic replicon...
June 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28261172/the-complement-system-in-flavivirus-infections
#19
Jonas N Conde, Emiliana M Silva, Angela S Barbosa, Ronaldo Mohana-Borges
The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical climates worldwide, affecting hundreds of millions of people each year. The Flaviviridae family includes dengue, West Nile, Zika, Japanese encephalitis, and yellow fever viruses that are typically transmitted by mosquitoes or ticks, and cause a wide range of symptoms, such as fever, shock, meningitis, paralysis, birth defects, and death. The flavivirus genome is composed of a single positive-sense RNA molecule encoding a single viral polyprotein...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28214373/improved-detection-of-zika-virus-rna-in-human-and-animal-specimens-by-a-novel-highly-sensitive-and-specific-real-time-rt-pcr-assay-targeting-the-5-untranslated-region-of-zika-virus
#20
Jasper Fuk-Woo Chan, Cyril Chik-Yan Yip, Kah-Meng Tee, Zheng Zhu, Jessica Oi-Ling Tsang, Kenn Ka-Heng Chik, Terance Gi-Wai Tsang, Chris Chung-Sing Chan, Vincent Kwok-Man Poon, Siddharth Sridhar, Feifei Yin, Ivan Fan-Ngai Hung, Sandy Ka-Yee Chau, Anna Jinxia Zhang, Kwok-Hung Chan, Kwok-Yung Yuen
OBJECTIVE AND METHOD: We developed and evaluated five novel real-time RT-PCR assays targeting conserved regions in the 5'-untranslated region (5'-UTR), envelope (E'), non-structural protein 2A (NS2A), NS5 and 3'-UTR of the ZIKV genome. RESULTS: The ZIKV-5'-UTR assay exhibited the lowest in vitro limit of detection (5-10 RNA copies/reaction and 3.0 × 10(-1) plaque-forming units/ml). Compared to the modified version of a widely adopted RT-PCR assay targeting the ZIKV-E gene, the ZIKV-5'-UTR assay showed better sensitivity in human clinical specimens, and representative mouse specimens, including many organs which are known to be involved in human ZIKV infection but difficult to obtain in clinical settings...
May 2017: Tropical Medicine & International Health: TM & IH
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