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Dengue immune evasion

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https://www.readbyqxmd.com/read/28515302/transposon-mutagenesis-of-the-zika-virus-genome-highlights-regions-essential-for-rna-replication-and-restricted-for-immune-evasion
#1
Benjamin O Fulton, David Sachs, Megan C Schwarz, Peter Palese, Matthew J Evans
The molecular constraints affecting Zika virus (ZIKV) evolution are not well understood. To investigate ZIKV genetic flexibility, we used transposon mutagenesis to add 15-nucleotide insertions throughout the MR766 ZIKV genome and subsequently deep sequenced the viable mutants. Few ZIKV insertion mutants replicated, which likely reflects a high degree of functional constraints on the genome. The NS1 gene exhibited distinct mutational tolerances at different stages of the screen. This result may define regions of the NS1 protein that are required for the different stages of the viral life cycle...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28465426/a-novel-agonist-of-the-trif-pathway-induces-a-cellular-state-refractory-to-replication-of-zika-chikungunya-and-dengue-viruses
#2
Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason Baird, Michael Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R DeFilippis
The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread...
May 2, 2017: MBio
https://www.readbyqxmd.com/read/28335410/non-canonical-roles-of-dengue-virus-non-structural-proteins
#3
REVIEW
Julianna D Zeidler, Lorena O Fernandes-Siqueira, Glauce M Barbosa, Andrea T Da Poian
The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes. This can be explained by the plurality of functions exerted by the few proteins coded by viral genomes, with some of these functions shared among members of a same family, but others being unique for each virus species. These non-canonical functions probably have evolved independently and may serve as the base to the development of specific therapies for each of those diseases...
March 13, 2017: Viruses
https://www.readbyqxmd.com/read/28327809/subversion-of-immunoproteasome-subunit-expression-in-dengue-virus-serotype-2-infected-hepg2-cells
#4
Chye Sheng Gan, Pei Jean Lim, Muhammad Fazril Mohamad Razif, Rohana Yusof, Shatrah Othman
INTRODUCTION: Infection with all serotypes of dengue virus (DV) results in augmented antigen presentation by MHC class I molecules. However, the upregulation of immunoproteasome subunits only results from infection with two serotypes. This study aims to elucidate changes in the expression of immunoproteasome subunits resulting from infection with DV, particularly DV serotype 2 (DV2). METHODS: HepG2 cells were grown in various culture milieu. Total cellular RNA and proteins were extracted and quantified...
January 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28264033/dengue-virus-genomic-variation-associated-with-mosquito-adaptation-defines-the-pattern-of-viral-non-coding-rnas-and-fitness-in-human-cells
#5
Claudia V Filomatori, Juan M Carballeda, Sergio M Villordo, Sebastian Aguirre, Horacio M Pallarés, Ana M Maestre, Irma Sánchez-Vargas, Carol D Blair, Cintia Fabri, Maria A Morales, Ana Fernandez-Sesma, Andrea V Gamarnik
The Flavivirus genus includes a large number of medically relevant pathogens that cycle between humans and arthropods. This host alternation imposes a selective pressure on the viral population. Here, we found that dengue virus, the most important viral human pathogen transmitted by insects, evolved a mechanism to differentially regulate the production of viral non-coding RNAs in mosquitos and humans, with a significant impact on viral fitness in each host. Flavivirus infections accumulate non-coding RNAs derived from the viral 3'UTRs (known as sfRNAs), relevant in viral pathogenesis and immune evasion...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28137230/proteases-in-mosquito-borne-diseases-new-avenues-in-drug-development
#6
A Pant, R Pasupureddy, V Pande, S Seshadri, R Dixit, K C Pandey
Mosquito borne diseases continue to propagate and cause millions of deaths annually. They are caused either by protozoan parasites such as Plasmodium, Toxoplasma or by flaviviruses including Dengue and Zika. Among the proteome of such parasitic organisms, proteases play essential roles in events such as host invasion, hemoglobin hydrolysis, replication and immune evasion. Plasmepsin V (PMV), an endoplasmic reticulum resident aspartic protease of Plasmodium spp., is involved in the export of ~400 proteins containing the conserved Plasmodium Export Element motif (PEXEL)...
January 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28128003/current-and-future-developments-in-the-treatment-of-virus-induced-hypercytokinemia
#7
Jonathan P Wong, Satya Viswanathan, Ming Wang, Lun-Quan Sun, Graeme C Clark, Riccardo V D'Elia
Emerging pathogenic viruses such as Ebola and Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) can cause acute infections through the evasion of the host's antiviral immune responses and by inducing the upregulation of inflammatory cytokines. This immune dysregulation, termed a cytokine storm or hypercytokinemia, is potentially fatal and is a significant underlying factor in increased mortality of infected patients. The prevalence of global outbreaks in recent years has offered opportunities to study the progression of various viral infections and have provided an improved understanding of hypercytokinemia associated with these diseases...
January 27, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/27798151/secreted-ns1-protects-dengue-virus-from-mannose-binding-lectin-mediated-neutralization
#8
Somchai Thiemmeca, Chamaiporn Tamdet, Nuntaya Punyadee, Tanapan Prommool, Adisak Songjaeng, Sansanee Noisakran, Chunya Puttikhunt, John P Atkinson, Michael S Diamond, Alongkot Ponlawat, Panisadee Avirutnan
Flavivirus nonstructural protein 1 (NS1) is a unique secreted nonstructural glycoprotein. Although it is absent from the flavivirus virion, intracellular and extracellular forms of NS1 have essential roles in viral replication and the pathogenesis of infection. The fate of NS1 in insect cells has been more controversial, with some reports suggesting it is exclusively cell associated. In this study, we confirm NS1 secretion from cells of insect origin and characterize its physical, biochemical, and functional properties in the context of dengue virus (DENV) infection...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27792906/innate-immune-escape-by-dengue-and-west-nile-viruses
#9
REVIEW
Michaela U Gack, Michael S Diamond
Dengue (DENV) and West Nile (WNV) viruses are mosquito-transmitted flaviviruses that cause significant morbidity and mortality worldwide. Disease severity and pathogenesis of DENV and WNV infections in humans depend on many factors, including pre-existing immunity, strain virulence, host genetics and virus-host interactions. Among the flavivirus-host interactions, viral evasion of type I interferon (IFN)-mediated innate immunity has a critical role in modulating pathogenesis. DENV and WNV have evolved effective strategies to evade immune surveillance pathways that lead to IFN induction and to block signaling downstream of the IFN-α/β receptor...
October 2016: Current Opinion in Virology
https://www.readbyqxmd.com/read/27716465/evasion-of-early-innate-immune-response-by-2-o-methylation-of-dengue-genomic-rna
#10
David C Chang, Long T Hoang, Ahmad Nazri Mohamed Naim, Hongping Dong, Mark J Schreiber, Martin L Hibberd, Min Jie Alvin Tan, Pei-Yong Shi
Dengue virus (DENV) is the most prevalent mosquito-borne virus pathogen in humans. There is currently no antiviral therapeutic or widely available vaccine against dengue infection. The DENV RNA genome is methylated on its 5' cap by its NS5 protein. DENV bearing a single E216A point mutation in NS5 loses 2'-O-methylation of its genome. While this mutant DENV is highly attenuated and immunogenic, the mechanism of this attenuation has not been elucidated. In this study, we find that replication of this mutant DENV is attenuated very early during infection...
December 2016: Virology
https://www.readbyqxmd.com/read/27702593/lipids-and-flaviviruses-present-and-future-perspectives-for-the-control-of-dengue-zika-and-west-nile-viruses
#11
REVIEW
Miguel A Martín-Acebes, Ángela Vázquez-Calvo, Juan-Carlos Saiz
Flaviviruses are emerging arthropod-borne pathogens that cause life-threatening diseases such as yellow fever, dengue, West Nile encephalitis, tick-borne encephalitis, Kyasanur Forest disease, tick-borne encephalitis, or Zika disease. This viral genus groups >50 viral species of small enveloped plus strand RNA virus that are phylogenetically closely related to hepatitis C virus. Importantly, the flavivirus life cycle is intimately associated to host cell lipids. Along this line, flaviviruses rearrange intracellular membranes from the endoplasmic-reticulum of the infected cells to develop adequate platforms for viral replication and particle biogenesis...
October 2016: Progress in Lipid Research
https://www.readbyqxmd.com/read/27666184/flavivirus-rna-transactions-from-viral-entry-to-genome-replication
#12
Mariano A Garcia-Blanco, Subhash G Vasudevan, Shelton S Bradrick, Christopher Nicchitta
Upon release of the ∼11 kb single-stranded positive polarity dengue virus genomic RNA (gRNA) into the cytoplasm of an infected cell, it serves as the template for translation of the viral polyprotein, which is cleaved into three structural and seven non-structural proteins. The structural organization of the viral replication complex and RNA is not known but it is increasingly becoming evident that the viral gRNA and replication intermediates adopt unique structural features and localize to discrete regions in the infected cell...
October 2016: Antiviral Research
https://www.readbyqxmd.com/read/27588756/nonstructural-proteins-are-preferential-positive-selection-targets-in-zika-virus-and-related-flaviviruses
#13
Manuela Sironi, Diego Forni, Mario Clerici, Rachele Cagliani
The Flavivirus genus comprises several human pathogens such as dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV). Although ZIKV usually causes mild symptoms, growing evidence is linking it to congenital birth defects and to increased risk of Guillain-Barré syndrome. ZIKV encodes a polyprotein that is processed to produce three structural and seven nonstructural (NS) proteins. We investigated the evolution of the viral polyprotein in ZIKV and in related flaviviruses (DENV, Spondweni virus, and Kedougou virus)...
September 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27578809/contribution-of-intertwined-loop-to-membrane-association-revealed-by-zika-virus-full-length-ns1-structure
#14
Xiaoying Xu, Hao Song, Jianxun Qi, Yuqian Liu, Haiyuan Wang, Chao Su, Yi Shi, George F Gao
The association of Zika virus (ZIKV) infections with microcephaly and neurological diseases has highlighted an emerging public health concern. Here, we report the crystal structure of the full-length ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis, and immune evasion. Of note, a long intertwined loop is observed in the wing domain of ZIKV NS1, and forms a hydrophobic "spike", which can contribute to cellular membrane association. For different flaviviruses, the amino acid sequences of the "spike" are variable but their common characteristic is either hydrophobic or positively charged, which is a beneficial feature for membrane binding...
October 17, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27575706/role-of-the-myeloid-differentiation-primary-response-myd88-and-tir-domain-containing-adapter-inducing-interferon-%C3%AE-trif-pathways-in-dengue
#15
Anyelo Duran, Nereida Valero, Jesus Mosquera, Lineth Delgado, Melchor Alvarez-Mon, Mariana Torres
AIMS: Dengue disease courses with high viremia titers and high cytokine production suggesting viral replication and active immune response that could be related to viral evasion. One of the main targets of dengue virus (DENV) is monocyte/macrophage cells; however, little information regarding viral evasive mechanisms and pathway activation in monocytes infected by DENV is available. The aim of this study was to determine the role of myeloid differentiation primary response (MyD88), TIR-domain-containing adapter- inducing interferon-β (TRIF) and NF-kB pathways in viral replication and cytokine production in human monocyte cultures infected by DENV2...
October 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27558165/autophagy-associated-dengue-vesicles-promote-viral-transmission-avoiding-antibody-neutralization
#16
Yan-Wei Wu, Clément Mettling, Shang-Rung Wu, Chia-Yi Yu, Guey-Chuen Perng, Yee-Shin Lin, Yea-Lih Lin
One of the major defense mechanisms against virus spread in vivo is the blocking of viral infectibility by neutralizing antibodies. We describe here the identification of infectious autophagy-associated dengue vesicles released from infected cells. These vesicles contain viral proteins E, NS1, prM/M, and viral RNA, as well as host lipid droplets and LC3-II, an autophagy marker. The viral RNA can be protected within the autophagic organelles since anti-dengue neutralizing antibodies do not have an effect on the vesicle-mediated transmission that is able to initiate a new round of infection in target cells...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27473856/flavivirus-ns1-a-multifaceted-enigmatic-viral-protein
#17
REVIEW
Meghana Rastogi, Nikhil Sharma, Sunit Kumar Singh
Flaviviruses are emerging arthropod-borne viruses representing an immense global health problem. The prominent viruses of this group include dengue virus, yellow fever virus, Japanese encephalitis virus, West Nile virus tick borne encephalitis virus and Zika Virus. These are endemic in many parts of the world. They are responsible for the illness ranging from mild flu like symptoms to severe hemorrhagic, neurologic and cognitive manifestations leading to death. NS1 is a highly conserved non-structural protein among flaviviruses, which exist in diverse forms...
July 29, 2016: Virology Journal
https://www.readbyqxmd.com/read/27252539/dengue-virus-subverts-host-innate-immunity-by-targeting-adaptor-protein-mavs
#18
Zhenjian He, Xun Zhu, Weitao Wen, Jie Yuan, Yiwen Hu, Jiahui Chen, Shu An, Xinhuai Dong, Cuiji Lin, Jianchen Yu, Jueheng Wu, Yi Yang, Junchao Cai, Jun Li, Mengfeng Li
UNLABELLED: Dengue virus (DENV) is the most common mosquito-borne virus infecting humans and is currently a serious global health challenge. To establish infection in its host cells, DENV must subvert the production and/or antiviral effects of interferon (IFN). The aim of this study was to understand the mechanisms by which DENV suppresses IFN production. We determined that DENV NS4A interacts with mitochondrial antiviral signaling protein (MAVS), which was previously found to activate NF-κB and IFN regulatory factor 3 (IRF3), thus inducing type I IFN in the mitochondrion-associated endoplasmic reticulum membranes (MAMs)...
August 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27233361/a-glance-at-subgenomic-flavivirus-rnas-and-micrornas-in-flavivirus-infections
#19
REVIEW
Lorena Bavia, Ana Luiza Pamplona Mosimann, Mateus Nóbrega Aoki, Claudia Nunes Duarte Dos Santos
The family Flaviviridae comprises a wide variety of viruses that are distributed worldwide, some of which are associated with high rates of morbidity and mortality. There are neither vaccines nor antivirals for most flavivirus infections, reinforcing the importance of research on different aspects of the viral life cycle. During infection, cytoplasmic accumulation of RNA fragments mainly originating from the 3' UTRs, which have been designated subgenomic flavivirus RNAs (sfRNAs), has been detected. It has been shown that eukaryotic exoribonucleases are involved in viral sfRNA production...
May 28, 2016: Virology Journal
https://www.readbyqxmd.com/read/27102744/correlating-flavivirus-virulence-and-levels-of-intrinsic-disorder-in-shell-proteins-protective-roles-vs-immune-evasion
#20
Gerard Kian-Meng Goh, A Keith Dunker, Vladimir N Uversky
Computational analyses revealed correlations between the intrinsic disorder propensity of shell proteins and case fatality rates (CFRs) among Flaviviruses and within at least two Flavivirus species, such as tick-borne encephalitis virus (TBEV) and dengue virus (DENV). The shell proteins analyzed in this study are capsid (C) and membrane (PrM, Pr, and M) proteins. The highest correlations can be found when regression analyses were conducted using Pr (Flavivirus: r(2) = 0.78, p < 0.01) or M (Flavivirus: r(2) = 0...
May 24, 2016: Molecular BioSystems
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