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https://www.readbyqxmd.com/read/29874999/inhibition-of-west-nile-virus-replication-by-bifunctional-sirna-targeting-the-ns2a-and-ns5-conserved-region
#1
Divyanshi Karothia, Paban Kumar Dash, M M Parida, Sameer Bhagyawant, Jyoti S Kumar
BACKGROUND: The West Nile virus (WNV) has emerged as one of the most significant arboviral infection in many parts of the world and is associated with the encephalitis affecting mainly human and horses. In spite of the fact that the WNV is threat for the public health, there is no vaccine or therapeutic available for the treatment of WNV. METHODS: In this study, we tested a novel RNA interference based technique to inhibit WNV replication in Vero cells. Two siRNAs were designed against the NS2A and NS5 region of WNV which are highly conserved among Flaviviruses as it play important role in apoptosis and in viral replication respectively...
June 6, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29868505/epidemiology-pathogenesis-and-control-of-a-tick-borne-disease-kyasanur-forest-disease-current-status-and-future-directions
#2
REVIEW
Syed Z Shah, Basit Jabbar, Nadeem Ahmed, Anum Rehman, Hira Nasir, Sarooj Nadeem, Iqra Jabbar, Zia Ur Rahman, Shafiq Azam
In South Asia, Haemaphysalis spinigera tick transmits Kyasanur Forest Disease Virus (KFDV), a flavivirus that causes severe hemorrhagic fever with neurological manifestations such as mental disturbances, severe headache, tremors, and vision deficits in infected human beings with a fatality rate of 3-10%. The disease was first reported in March 1957 from Kyasanur forest of Karnataka (India) from sick and dying monkeys. Since then, between 400 and 500 humans cases per year have been recorded; monkeys and small mammals are common hosts of this virus...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29845532/establishment-and-application-of-flavivirus-replicons
#3
Beate M Kümmerer
Dengue virus (DENV) and Zika virus (ZIKV) are enveloped, positive-strand RNA viruses belonging to the genus Flavivirus in the family Flaviviridae. The genome of ~11 kb length encodes one long open reading frame flanked by a 5' and a 3' untranslated region (UTR). The 5' end is capped and the 3' end lacks a poly(A) tail. The encoded single polyprotein is cleaved co-and posttranslationally by cellular and viral proteases. The first one-third of the genome encodes the structural proteins (C-prM-E), whereas the nonstructural (NS) proteins NS1-NS2A-NS3-NS4A-2K-NS4B-NS5 are encoded by the remaining two-thirds of the genome...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29789537/detection-of-japanese-encephalitis-virus-rna-in-human-throat-samples-in-laos-a-pilot-study
#4
Tehmina Bharucha, Onanong Sengvilaipaseuth, Malee Seephonelee, Malavanh Vongsouvath, Manivanh Vongsouvath, Sayaphet Rattanavong, Géraldine Piorkowski, Marc Lecuit, Christopher Gorman, Jean-David Pommier, Paul N Newton, Xavier de Lamballerie, Audrey Dubot-Pérès
Japanese encephalitis virus (JEV) is the most commonly identified cause of acute encephalitis syndrome (AES) in Asia. The WHO recommended test is anti-JEV IgM-antibody-capture-enzyme-linked-immunosorbent-assay (JEV MAC-ELISA). However, data suggest this has low positive predictive value, with false positives related to other Flavivirus infections and vaccination. JEV RT-PCR in cerebrospinal fluid (CSF) and/or serum is highly specific, but is rarely positive; 0-25% of patients that fulfil the WHO definition of JE (clinical Acute Encephalitis Syndrome (AES) and JEV MAC-ELISA positive)...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29699483/emergence-of-the-asian-lineage-dengue-virus-type-3-genotype-iii-in-malaysia
#5
Kim-Kee Tan, Nurul-Izzani Zulkifle, Syuhaida Sulaiman, Sui-Ping Pang, NurAsyura NorAmdan, NorAziyah MatRahim, Juraina Abd-Jamil, Meng-Hooi Shu, Nor Muhammad Mahadi, Sazaly AbuBakar
BACKGROUND: Dengue virus type 3 genotype III (DENV3/III) is associated with increased number of severe infections when it emerged in the Americas and Asia. We had previously demonstrated that the DENV3/III was introduced into Malaysia in the late 2000s. We investigated the genetic diversity of DENV3/III strains recovered from Malaysia and examined their phylogenetic relationships against other DENV3/III strains isolated globally. RESULTS: Phylogenetic analysis revealed at least four distinct DENV3/III lineages...
April 24, 2018: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/29674002/dengue-virus-ns2-and-ns4-minor-proteins-mammoth-roles
#6
REVIEW
Sindhoora Bhargavi Gopala Reddy, Wei-Xin Chin, Nanjunda Swamy Shivananju
Despite the ever-increasing global incidence of dengue fever, there are no specific chemotherapy regimens for its treatment. Structural studies on dengue virus (DENV) proteins have revealed potential drug targets. Major DENV proteins such as the envelope protein and non-structural (NS) proteins 3 and 5 have been extensively investigated in antiviral studies, but with limited success in vitro. However, the minor NS proteins NS2 and NS4 have remained relatively underreported. Emerging evidence indicating their indispensable roles in virus propagation and host immunomodulation should encourage us to target these proteins for drug discovery...
April 17, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29655579/hungarian-tick-borne-encephalitis-viruses-isolated-from-a-0-5-ha-focus-are-closely-related-to-finnish-strains
#7
László Egyed, Zsuzsanna Rónai, Ádám Dán
Four tick-borne encephalitis virus strains were isolated from a small 0.5-ha focus over a six-year-long period (2011-2016) in Hungary. Two strains with identical genomes were isolated from Ixodes ricinus and Haemaphysalis concinna two months apart, which shows that the virus had not evolved separately in these tick species. Whole-genome sequencing of the virus revealed that the isolates differed from each other in 4 amino acids and 9 nucleotides. The calculated substitution rates indicated that the speed of genome evolution differs from habitat to habitat, and continuously changes even within the same focus...
April 7, 2018: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/29619598/pcr-array-profiling-of-antiviral-genes-in-human-embryonic-kidney-cells-expressing-human-coronavirus-oc43-structural-and-accessory-proteins
#8
Meshal Beidas, Wassim Chehadeh
Human coronavirus OC43 (HCoV-OC43) is a respiratory virus that usually causes a common cold. However, it has the potential to cause severe infection in young children and immunocompromised adults. Both SARS-CoV and MERS-CoV were shown to express proteins with the potential to evade early innate immune responses. However, the ability of HCoV-OC43 to antagonise the intracellular antiviral defences has not yet been investigated. The potential role of the HCoV-OC43 structural (M and N) and accessory proteins (ns2a and ns5a) in the alteration of antiviral gene expression was investigated in this study...
April 4, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29593046/host-factor-spcs1-regulates-the-replication-of-japanese-encephalitis-virus-through-interactions-with-transmembrane-domains-of-ns2b
#9
Le Ma, Fang Li, Jing-Wei Zhang, Wei Li, Dong-Ming Zhao, Han Wang, Rong-Hong Hua, Zhi-Gao Bu
Signal peptidase complex subunit 1 (SPCS1) is a newly identified host factor that regulates flavivirus replication, but the molecular mechanism is not fully understood. Here, using Japanese encephalitis virus (JEV) as a model, we investigated the mechanism through which the host factor SPCS1 regulates the replication of flaviviruses. We first validated the regulatory function of SPCS1 in JEV propagation by knocking down and knocking out endogenous SPCS1. The loss of SPCS1 function markedly reduced intracellular virion assembly and the production of infectious JEV particles but did not affect cell entry, RNA replication, or translation of the virus...
June 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29570739/development-of-an-improved-rt-qpcr-assay-for-detection-of-japanese-encephalitis-virus-jev-rna-including-a-systematic-review-and-comprehensive-comparison-with-published-methods
#10
Tehmina Bharucha, Onanong Sengvilaipaseuth, Manivanh Vongsouvath, Malavanh Vongsouvath, Viengmon Davong, Phonepasith Panyanouvong, Géraldine Piorkowski, Jeremy A Garson, Paul N Newton, Xavier de Lamballerie, Audrey Dubot-Pérès
BACKGROUND: Japanese encephalitis virus (JEV) is a major cause of encephalitis in Asia, and the commonest cause of mosquito-borne encephalitis worldwide. Detection of JEV RNA remains challenging due to the characteristic brief and low viraemia, with 0-25% of patients positive, and the mainstay of diagnosis remains detection of anti-JEV IgM antibody. METHODS: We performed a systematic review of published RT-PCR protocols, and evaluated them in silico and in vitro alongside new primers and probes designed using a multiple genome alignment of all JEV strains >9,000nt from GenBank, downloaded from the NCBI website (November 2016)...
2018: PloS One
https://www.readbyqxmd.com/read/29379028/an-evolutionary-ns1-mutation-enhances-zika-virus-evasion-of-host-interferon-induction
#11
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
#12
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...
April 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29147783/new-virus-of-the-family-flaviviridae-detected-in-lumpfish-cyclopterus-lumpus
#13
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...
March 2018: Archives of Virology
https://www.readbyqxmd.com/read/29141913/multiplexed-biomarker-panels-discriminate-zika-and-dengue-virus-infection-in-humans
#14
Guang Song, Hee-Sool Rho, Jianbo Pan, Pedro Ramos, Ki-Jun Yoon, Freddy A Medina, Emily M Lee, Daniel 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...
February 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29094318/discovery-of-t-cell-driven-subunit-vaccines-from-zika-virus-genome-an-immunoinformatics-approach
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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.
October 3, 2017: Virulence
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