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Flavivirus assembly

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https://www.readbyqxmd.com/read/28715409/zika-virus-inhibits-eif2%C3%AE-dependent-stress-granule-assembly
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28198446/a-mutation-identified-in-neonatal-microcephaly-destabilizes-zika-virus-ns1-assembly-in-vitro
#14
Deping Wang, Cheng Chen, Shengnan Liu, Han Zhou, Kailin Yang, Qi Zhao, Xiaoyun Ji, Chen Chen, Wei Xie, Zefang Wang, Li-Zhi Mi, Haitao Yang
An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1172-352, which forms a head-to-head, symmetric dimer with a unique 14-stranded β-ladder conserved among flaviviruses...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196656/a-cdna-clone-launched-platform-for-high-yield-production-of-inactivated-zika-vaccine
#15
Yujiao Yang, Chao Shan, Jing Zou, Antonio E Muruato, Diniz Nunes Bruno, Barbosa de Almeida Medeiros Daniele, Pedro F C Vasconcelos, Shannan L Rossi, Scott C Weaver, Xuping Xie, Pei-Yong Shi
A purified inactivated vaccine (PIV) using the Zika virus (ZIKV) Puerto Rico strain PRVABC59 showed efficacy in monkeys, and is currently in a phase I clinical trial. High-yield manufacture of this PIV is essential for its development and vaccine access. Here we report an infectious cDNA clone-launched platform to maximize its yield. A single NS1 protein substitution (K265E) was identified to increase ZIKV replication on Vero cells (a cell line approved for vaccine production) for both Cambodian FSS13025 and Puerto Rico PRVABC59 strains...
March 2017: EBioMedicine
https://www.readbyqxmd.com/read/28174309/understanding-zika-virus-stability-and-developing-a-chimeric-vaccine-through-functional-analysis
#16
Xuping Xie, Yujiao Yang, Antonio E Muruato, Jing Zou, Chao Shan, Bruno T D Nunes, Daniele B A Medeiros, Pedro F C Vasconcelos, Scott C Weaver, Shannan L Rossi, Pei-Yong Shi
Compared with other flaviviruses, Zika virus (ZIKV) is uniquely associated with congenital diseases in pregnant women. One recent study reported that (i) ZIKV has higher thermostability than dengue virus (DENV [a flavivirus closely related to ZIKV]), which might contribute to the disease outcome; (ii) the higher thermostability of ZIKV could arise from an extended loop structure in domain III of the viral envelope (E) protein and an extra hydrogen-bond interaction between E molecules (V. A. Kostyuchenko, E...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28137230/proteases-in-mosquito-borne-diseases-new-avenues-in-drug-development
#17
REVIEW
A Pant, R Pasupureddy, V Pande, S Seshadri, R Dixit, K C Pandey
INTRODUCTION: 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)...
2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28124222/recent-advances-in-the-identification-of-the-host-factors-involved-in-dengue-virus-replication
#18
REVIEW
Yi Wang, Ping Zhang
Dengue virus (DENV) belongs to the genus Flavivirus of the family Flaviviridae and it is primarily transmitted via Aedes aegypti and Aedes albopictus mosquitoes. The life cycle of DENV includes attachment, endocytosis, protein translation, RNA synthesis, assembly, egress, and maturation. Recent researches have indicated that a variety of host factors, including cellular proteins and microRNAs, positively or negatively regulate the DENV replication process. This review summarizes the latest findings (from 2014 to 2016) in the identification of the host factors involved in the DENV life cycle and Dengue infection...
February 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28102736/dengue-and-zika-viruses-subvert-reticulophagy-by-ns2b3-mediated-cleavage-of-fam134b
#19
Nicholas J Lennemann, Carolyn B Coyne
The endoplasmic reticulum (ER) is exploited by several diverse viruses during their infectious life cycles. Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), utilize the ER as a source of membranes to establish their replication organelles and to facilitate their assembly and eventual maturation along the secretory pathway. To maintain normal homeostasis, host cells have evolved highly efficient processes to dynamically regulate the ER, such as through reticulophagy, a selective form of autophagy that leads to ER degradation...
February 2017: Autophagy
https://www.readbyqxmd.com/read/28101536/host-range-restriction-of-insect-specific-flaviviruses-occurs-at-several-levels-of-the-viral-life-cycle
#20
Sandra Junglen, Marvin Korries, Wolfgang Grasse, Janett Wieseler, Anne Kopp, Kyra Hermanns, Moises León-Juárez, Christian Drosten, Beate Mareike Kümmerer
The genus Flavivirus contains emerging arthropod-borne viruses (arboviruses) infecting vertebrates, as well as insect-specific viruses (ISVs) (i.e., viruses whose host range is restricted to insects). ISVs are evolutionary precursors to arboviruses. Knowledge of the nature of the ISV infection block in vertebrates could identify functions necessary for the expansion of the host range toward vertebrates. Mapping of host restrictions by complementation of ISV and arbovirus genome functions could generate knowledge critical to predicting arbovirus emergence...
January 2017: MSphere
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