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Flavivirus assembly

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https://www.readbyqxmd.com/read/29610346/flavivirus-internalization-is-regulated-by-a-size-dependent-endocytic-pathway
#1
Brent A Hackett, Sara Cherry
Flaviviruses enter host cells through the process of clathrin-mediated endocytosis, and the spectrum of host factors required for this process are incompletely understood. Here we found that lymphocyte antigen 6 locus E (LY6E) promotes the internalization of multiple flaviviruses, including West Nile virus, Zika virus, and dengue virus. Perhaps surprisingly, LY6E is dispensable for the internalization of the endogenous cargo transferrin, which is also dependent on clathrin-mediated endocytosis for uptake. Since viruses are substantially larger than transferrin, we reasoned that LY6E may be required for uptake of larger cargoes and tested this using transferrin-coated beads of similar size as flaviviruses...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29593046/host-factor-spcs1-regulates-the-replication-of-japanese-encephalitis-virus-through-interactions-with-transmembrane-domains-of-ns2b
#2
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. Herein, using Japanese encephalitis virus (JEV) as a model, we investigated the mechanism through which 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. Loss of SPCS1 function markedly reduced intracellular virion assembly and production of infectious JEV particles, but did not affect virus cell entry, RNA replication, or translation...
March 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29563905/molecular-basis-of-encapsidation-of-hepatitis-c-virus-genome
#3
REVIEW
Guoli Shi, Tetsuro Suzuki
Hepatitis C virus (HCV), a major etiologic agent of human liver diseases, is a positive-sense single-stranded RNA virus and is classified in the Flaviviridae family. Although research findings for the assembly of HCV particles are accumulating due to development of HCV cell culture system, the mechanism(s) by which the HCV genome becomes encapsidated remains largely unclear. In general, viral RNA represents only a small fraction of the RNA molecules in the cells infected with RNA viruses, but the viral genomic RNA is considered to selectively packaged into virions...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29454707/crystal-structure-of-the-capsid-protein-from-zika-virus
#4
Zifang Shang, Hao Song, Yi Shi, Jianxun Qi, George F Gao
Recently, Zika virus (ZIKV) emerged as a global public health concern, and is distinct from other flaviviruses in many aspects, e.g., causing transplacental infection, fetal abnormalities and vector-independent transmission through body fluids in humans. The capsid (C) protein is a multifunctional protein, since it binds to viral RNA in the process of nucleocapsid assembly and plays important roles in virus infection processes by interacting with cellular proteins, modulating cellular metabolism, apoptosis and immune response...
February 15, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29447265/dynamic-remodeling-of-lipids-coincides-with-dengue-virus-replication-in-the-midgut-of-aedes-aegypti-mosquitoes
#5
Nunya Chotiwan, Barbara G Andre, Irma Sanchez-Vargas, M Nurul Islam, Jeffrey M Grabowski, Amber Hopf-Jannasch, Erik Gough, Ernesto Nakayasu, Carol D Blair, John T Belisle, Catherine A Hill, Richard J Kuhn, Rushika Perera
We describe the first comprehensive analysis of the midgut metabolome of Aedes aegypti, the primary mosquito vector for arboviruses such as dengue, Zika, chikungunya and yellow fever viruses. Transmission of these viruses depends on their ability to infect, replicate and disseminate from several tissues in the mosquito vector. The metabolic environments within these tissues play crucial roles in these processes. Since these viruses are enveloped, viral replication, assembly and release occur on cellular membranes primed through the manipulation of host metabolism...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29323278/structural-biology-of-zika-virus-and-other-flaviviruses
#6
REVIEW
S Saif Hasan, Madhumati Sevvana, Richard J Kuhn, Michael G Rossmann
Zika virus (ZIKV) is an enveloped, icosahedral flavivirus that has structural and functional similarities to other human flavivirus pathogens such as dengue (DENV), West Nile (WNV) and Japanese encephalitis (JEV) viruses. ZIKV infections have been linked to fetal microcephaly and the paralytic Guillain-Barré syndrome. This review provides a comparative structural analysis of the assembly, maturation and host-cell entry of ZIKV with other flaviviruses, especially DENV. We also discuss the mechanisms of neutralization by antibodies...
January 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29300359/geometric-defects-and-icosahedral-viruses
#7
REVIEW
Joseph Che-Yen Wang, Suchetana Mukhopadhyay, Adam Zlotnick
We propose that viruses with geometric defects are not necessarily flawed viruses. A geometric defect may be a reactive site. Defects may facilitate assembly, dissociation, or accessibility of cellular proteins to virion components. In single molecule studies of hepadnavirus assembly, defects and overgrowth are common features. Icosahedral alphaviruses and flaviviruses, among others, have capsids with geometric defects. Similarly, immature retroviruses, which are non-icosahedral, have numerous "errors"...
January 4, 2018: Viruses
https://www.readbyqxmd.com/read/29234310/modulation-of-lipid-droplet-metabolism-a-potential-target-for-therapeutic-intervention-in-flaviviridae-infections
#8
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
#9
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
#10
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-hepatitis-c-virus-strain-jfh-1-is-an-unusually-robust-helicase-that-is-primed-to-bind-and-unwind-viral-rna
#11
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 (nonstructural protein 3 [NS3]). This helicase has become the focus of extensive basic research on the 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...
January 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29046456/viperin-targets-flavivirus-virulence-by-inducing-assembly-of-non-infectious-capsid-particles
#12
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
#13
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
#14
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...
January 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/28715409/zika-virus-inhibits-eif2%C3%AE-dependent-stress-granule-assembly
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
July 2017: Antiviral Research
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