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Flavivirus assembly

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https://www.readbyqxmd.com/read/29234310/modulation-of-lipid-droplet-metabolism-a-potential-target-for-therapeutic-intervention-in-flaviviridae-infections
#1
REVIEW
Jingshu Zhang, Yun Lan, Sumana Sanyal
Lipid droplets (LDs) are endoplasmic reticulum (ER)-related dynamic organelles that store and regulate fatty acids and neutral lipids. They play a central role in cellular energy storage, lipid metabolism and cellular homeostasis. It has become evident that viruses have co-evolved in order to exploit host lipid metabolic pathways. This is especially characteristic of the Flaviviridae family, including hepatitis C virus (HCV) and several flaviviruses. Devoid of an appropriate lipid biosynthetic machinery of their own, these single-strand positive-sense RNA viruses can induce dramatic changes in host metabolic pathways to establish a favorable environment for viral multiplication and acquire essential components to facilitate their assembly and traffic...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29099073/helicase-domain-of-west-nile-virus-ns3-protein-plays-a-role-in-inhibition-of-type-i-interferon-signalling
#2
Yin Xiang Setoh, Parthiban Periasamy, Nias Yong Gao Peng, Alberto A Amarilla, Andrii Slonchak, Alexander A Khromykh
West Nile virus (WNV) is a neurotropic flavivirus that can cause encephalitis in mammalian and avian hosts. In America, the virulent WNV strain (NY99) is causing yearly outbreaks of encephalitis in humans and horses, while in Australia the less virulent Kunjin strain of WNV strain has not been associated with significant disease outbreaks until a recent 2011 large outbreak in horses (but not in humans) caused by NSW2011 strain. Using chimeric viruses between NY99 and NSW2011 strains we previously identified a role for the non-structural proteins of NY99 strain and especially the NS3 protein, in enhanced virus replication in type I interferon response-competent cells and increased virulence in mice...
November 2, 2017: Viruses
https://www.readbyqxmd.com/read/29074234/development-of-a-rapid-and-quantitative-method-for-the-analysis-of-viral-entry-and-release-using-a-nanoluc-luciferase-complementation-assay
#3
Michihito Sasaki, Paulina D Anindita, Wallaya Phongphaew, Michael Carr, Shintaro Kobayashi, Yasuko Orba, Hirofumi Sawa
Subviral particles (SVPs) self-assemble and are released from cells transfected with expression plasmids encoding flavivirus structural proteins. Flavivirus-like particles (VLPs), consisting of flavivirus structural proteins and a subgenomic replicon, can enter cells and cause single-round infections. Neither SVPs or VLPs possess complete viral RNA genomes, therefore are replication-incompetent systems; however, they retain the capacity to fuse and bud from target cells and follow the same maturation process as whole virions...
October 23, 2017: Virus Research
https://www.readbyqxmd.com/read/29070684/ns3-from-hcv-strain-jfh-1-is-an-unusually-robust-helicase-that-is-primed-to-bind-and-unwind-viral-rna
#4
Ting Zhou, Xiaoming Ren, Rebecca L Adams, Anna Marie Pyle
Hepatitis C viruses (HCV) encode a helicase enzyme that is essential for viral replication and assembly (NS3). This helicase has become the focus of extensive basic research on general helicase mechanism and it is also of interest as a novel drug target. Despite the importance of this protein, mechanistic work on NS3 has been conducted almost exclusively on variants from HCV genotype 1. Our understanding of NS3 from the highly active HCV strains that are used to study HCV genetics and mechanism in cell culture (such as JFH-1) is lacking...
October 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29046456/viperin-targets-flavivirus-virulence-by-inducing-assembly-of-non-infectious-capsid-particles
#5
Kirstin Vonderstein, Emma Nilsson, Philipp Hubel, Lars Nygård Skalman, Arunkumar Upadhyay, Jenny Pasto, Andreas Pichlmair, Richard Lundmark, Anna K Överby
Efficient antiviral immunity requires interference with virus replication at multiple layers targeting diverse steps in the viral life cycle. Here we describe a novel flavivirus inhibition mechanism that results in interferon-mediated obstruction of tick-borne encephalitis virus particle assembly, and involves release of malfunctional membrane associated capsid (C) particles. This mechanism is controlled by the activity of the interferon-induced protein viperin, a broad spectrum antiviral interferon stimulated gene...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29022864/reverse-genetic-system-genetically-stable-reporter-viruses-and-packaged-subgenomic-replicon-based-on-a-brazilian-zika-virus-isolate
#6
Margit Mutso, Sirle Saul, Kai Rausalu, Olga Susova, Eva Žusinaite, Suresh Mahalingam, Andres Merits
Zika virus (ZIKV, genus Flavivirus) has emerged as a major mosquito-transmitted human pathogen, with recent outbreaks associated with an increased incidence of neurological complications, particularly microcephaly and the Guillain-Barré syndrome. Because the virus has only very recently emerged as an important pathogen, research is being hampered by a lack of reliable molecular tools. Here we report an infectious cDNA (icDNA) clone for ZIKV isolate BeH819015 from Brazil, which was selected as representative of South American ZIKV isolated at early stages of the outbreak...
November 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28916391/zika-virus-structural-biology-and-progress-in-vaccine-development
#7
REVIEW
Hsiao-Han Lin, Bak-Sau Yip, Li-Min Huang, Suh-Chin Wu
The growing number of zika virus (ZIKV) infections plus a 20-fold increase in neonatal microcephaly in newborns in Brazil have raised alarms in many countries regarding the threat to pregnant women. Instances of microcephaly and central nervous system malformations continue to increase in ZIKV outbreak regions. ZIKV is a small enveloped positive-strand RNA virus belonging to the Flavivirus genus of the Flaviviridae family. High-resolution ZIKV structures recently identified by cryo-electron microscopy indicate that the overall ZIKV structure is similar to those of other flaviviruses...
September 12, 2017: Biotechnology Advances
https://www.readbyqxmd.com/read/28715409/zika-virus-inhibits-eif2%C3%AE-dependent-stress-granule-assembly
#8
Raquel Amorim, Abdelkrim Temzi, Bryan D Griffin, Andrew J Mouland
Zika virus (ZIKV), a member of the Flaviviridae family, is the most recent emerging arbovirus with pandemic potential. During infection, viruses trigger the host cell stress response, leading to changes in RNA translation and the assembly of large aggregates of stalled translation preinitiation complexes, termed stress granules (SGs). Several reports demonstrate that flaviviruses modulate the assembly of stress granules (SG). As an emerging pathogen, little is known however about how ZIKV modulates the host cell stress response...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28674411/in-vitro-assembly-and-stabilization-of-dengue-and-zika-virus-envelope-protein-homo-dimers
#9
Stefan W Metz, Emily N Gallichotte, Alex Brackbill, Lakshmanane Premkumar, Michael J Miley, Ralph Baric, Aravinda M de Silva
Zika virus (ZIKV) and the 4 dengue virus (DENV) serotypes are mosquito-borne Flaviviruses that are associated with severe neuronal and hemorrhagic syndromes. The mature flavivirus infectious virion has 90 envelope (E) protein homo-dimers that pack tightly to form a smooth protein coat with icosahedral symmetry. Human antibodies that strongly neutralize ZIKV and DENVs recognize complex quaternary structure epitopes displayed on E-homo-dimers and higher order structures. The ZIKV and DENV E protein expressed as a soluble protein is mainly a monomer that does not display quaternary epitopes, which may explain the modest success with soluble recombinant E (sRecE) as a vaccine and diagnostic antigen...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673021/emergence-of-west-nile-virus-in-west-bengal-india-a-new-report
#10
Tanuja Khatun, Shyamalendu Chatterjee
Background: The ICMR virus unit in Kolkata functions as an Appex Referral Laboratory for the detection of dengue (DENV) and chikungunya (CHIKV) infections in the eastern part of India. In spite of efforts for confirmatory diagnosis, some samples remain undiagnosed every year. West Nile virus (WNV) infection may mimic either dengue (flavivirus) or chikungunya (alphavirus) like illness. WNV is endemic in the tropical region where its principal/potential vectors are Aedes and Culex. Methods: We explored the existence of WNV within undiagnosed samples to identify the emergence of a new public health problem...
April 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28656015/bip-master-regulator-of-the-unfolded-protein-response-and-crucial-factor-in-flavivirus-biology%C3%A2
#11
REVIEW
Tyler G Lewy, Jeffrey M Grabowski, Marshall E Bloom
Flaviviruses have an intimate relationship with their host cells, utilizing host proteins during replication. Much of viral genome replication and virion assembly occurs on and within the endoplasmic reticulum (ER). As a cellular protein folding hub, the ER provides an ideal environment for flaviviruses to replicate. Flaviviruses can interact with several ER processes, including the unfolded protein response (UPR), a cellular stress mechanism responsible for managing unfolded protein accumulation and ER stress...
June 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28592527/zika-virus-hijacks-stress-granule-proteins-and-modulates-the-host-stress-response
#12
Shangmei Hou, Anil Kumar, Zaikun Xu, Adriana M Airo, Iryna Stryapunina, Cheung Pang Wong, William Branton, Egor Tchesnokov, Matthias Götte, Christopher Power, Tom C Hobman
Zika virus (ZIKV), a member of the Flaviviridae family, has recently emerged as an important human pathogen with increasing economic and health impact worldwide. Because of its teratogenic nature and association with the serious neurological condition Guillain-Barré syndrome, a tremendous amount of effort has focused on understanding ZIKV pathogenesis. To gain further insights into ZIKV interaction with host cells, we investigated how this pathogen affects stress response pathways. While ZIKV infection induces stress signaling that leads to phosphorylation of eIF2α and cellular translational arrest, stress granule (SG) formation was inhibited...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28461071/host-oxidative-folding-pathways-offer-novel-anti-chikungunya-virus-drug-targets-with-broad-spectrum-potential
#13
Rose M Langsjoen, Albert J Auguste, Shannan L Rossi, Christopher M Roundy, Heidy N Penate, Maria Kastis, Matthew K Schnizlein, Kevin C Le, Sherry L Haller, Rubing Chen, Stanley J Watowich, Scott C Weaver
Alphaviruses require conserved cysteine residues for proper folding and assembly of the E1 and E2 envelope glycoproteins, and likely depend on host protein disulfide isomerase-family enzymes (PDI) to aid in facilitating disulfide bond formation and isomerization in these proteins. Here, we show that in human HEK293 cells, commercially available inhibitors of PDI or modulators thereof (thioredoxin reductase, TRX-R; endoplasmic reticulum oxidoreductin-1, ERO-1) inhibit the replication of CHIKV chikungunya virus (CHIKV) in vitro in a dose-dependent manner...
April 28, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28441781/dengue-virus-non-structural-protein-5
#14
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/28424472/temperature-dependent-folding-allows-stable-dimerization-of-secretory-and-virus-associated-e-proteins-of-dengue-and-zika-viruses-in-mammalian-cells
#15
J L Slon Campos, S Marchese, J Rana, M Mossenta, M Poggianella, M Bestagno, O R Burrone
Dengue and Zika are two of the most important human viral pathogens worldwide. In both cases, the envelope glycoprotein E is the main target of the antibody response. Recently, new complex quaternary epitopes were identified which are the consequence of the arrangement of the antiparallel E dimers on the viral surface. Such epitopes can be exploited to develop more efficient cross-neutralizing vaccines. Here we describe a successful covalent stabilization of E dimers from Dengue and Zika viruses in mammalian cells...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28388487/characterization-of-virus-specific-vesicles-assembled-by-west-nile-virus-non-structural-proteins
#16
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
#17
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/28318141/zika-virus-induced-cellular-remodelling
#18
Evan D Rossignol, Kristen N Peters, John H Connor, Esther Bullitt
Zika virus (ZIKV) has been associated with morbidities such as Guillain-Barré, infant microcephaly, and ocular disease. The spread of this positive-sense, single-stranded RNA virus and its growing public health threat underscore gaps in our understanding of basic ZIKV virology. To advance knowledge of the virus replication cycle within mammalian cells, we use serial section 3-dimensional electron tomography to demonstrate the widespread remodelling of intracellular membranes upon infection with ZIKV. We report extensive structural rearrangements of the endoplasmic reticulum and reveal stages of the ZIKV viral replication cycle...
August 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28251184/epitope-addition-and-ablation-via-manipulation-of-a-dengue-virus-serotype-1-infectious-clone
#19
Emily N Gallichotte, Vineet D Menachery, Boyd L Yount, Douglas G Widman, Kenneth H Dinnon, Steven Hartman, Aravinda M de Silva, Ralph S Baric
Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses...
January 2017: MSphere
https://www.readbyqxmd.com/read/28241074/arsenite-induced-stress-granule-formation-is-inhibited-by-elevated-levels-of-reduced-glutathione-in-west-nile-virus-infected-cells
#20
Mausumi Basu, Sean C Courtney, Margo A Brinton
Oxidative stress activates the cellular kinase HRI, which then phosphorylates eIF2α, resulting in stalled translation initiation and the formation of stress granules (SGs). SG assembly redirects cellular translation to stress response mRNAs and inhibits cap-dependent viral RNA translation. Flavivirus infections were previously reported to induce oxidative stress in infected cells but flavivirus-infected cells paradoxically develop resistance to arsenite (Ars)-induced SG formation with time after infection...
February 2017: PLoS Pathogens
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