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https://www.readbyqxmd.com/read/28534487/rules-of-engagement-between-%C3%AE-v%C3%AE-6-integrin-and-foot-and-mouth-disease-virus
#1
Abhay Kotecha, Quan Wang, Xianchi Dong, Serban L Ilca, Marina Ondiviela, Rao Zihe, Julian Seago, Bryan Charleston, Elizabeth E Fry, Nicola G A Abrescia, Timothy A Springer, Juha T Huiskonen, David I Stuart
Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1. Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections. HS interaction has been visualized at a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28533400/the-pentameric-complex-drives-immunologically-covert-cell-cell-transmission-of-wild-type-human-cytomegalovirus
#2
Isa Murrell, Carmen Bedford, Kristin Ladell, Kelly L Miners, David A Price, Peter Tomasec, Gavin W G Wilkinson, Richard J Stanton
Human cytomegalovirus (HCMV) strains that have been passaged in vitro rapidly acquire mutations that impact viral growth. These laboratory-adapted strains of HCMV generally exhibit restricted tropism, produce high levels of cell-free virus, and develop susceptibility to natural killer cells. To permit experimentation with a virus that retained a clinically relevant phenotype, we reconstructed a wild-type (WT) HCMV genome using bacterial artificial chromosome technology. Like clinical virus, this genome proved to be unstable in cell culture; however, propagation of intact virus was achieved by placing the RL13 and UL128 genes under conditional expression...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28531161/development-of-optimized-inhibitor-rnas-allowing-multisite-targeting-of-the-hcv-genome
#3
Cristina Romero-López, Thomas Lahlali, Beatriz Berzal-Herranz, Alfredo Berzal-Herranz
Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in drugs with potentially enhanced therapeutic properties. In the present work, the anti-HCV chimeric inhibitor RNA HH363-10, which has a hammerhead catalytic domain and an aptamer RNA domain, was subjected to an in vitro selection strategy to isolate ten different optimised chimeric inhibitor RNAs...
May 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28528686/hpv-entry-into-cells
#4
REVIEW
Pinar Aksoy, Elinor Y Gottschalk, Patricio I Meneses
Human papillomavirus (HPV) is a sexually transmitted virus responsible for the development of cervical cancer, anal cancer, head and throat cancers, as well as genital area warts. A major focus of current HPV research is on preventing the virus from entering a cell and transferring its genetic material to the nucleus, thus potentially preventing the development of cancer. Although the available HPV vaccines are extremely successful, approximately 15 additional cancer-causing HPVs have been identified that the vaccines do not protect against...
April 2017: Mutation Research
https://www.readbyqxmd.com/read/28528445/interindividual-spread-of-herpesviruses
#5
Keith W Jarosinski
Interindividual spread of herpesviruses is essential for the virus life cycle and maintenance in host populations. For most herpesviruses, the virus-host relationship is close, having coevolved over millions of years resulting in comparatively high species specificity. The mechanisms governing interindividual spread or horizontal transmission are very complex, involving conserved herpesviral and cellular proteins during the attachment, entry, replication, and egress processes of infection. Also likely, specific herpesviruses have evolved unique viral and cellular interactions during cospeciation that are dependent on their relationship...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528444/assembly-and-egress-of-an-alphaherpesvirus-clockwork
#6
Gregory A Smith
All viruses produce infectious particles that possess some degree of stability in the extracellular environment yet disassemble upon cell contact and entry. For the alphaherpesviruses, which include many neuroinvasive viruses of mammals, these metastable virions consist of an icosahedral capsid surrounded by a protein matrix (referred to as the tegument) and a lipid envelope studded with glycoproteins. Whereas the capsid of these viruses is a rigid structure encasing the DNA genome, the tegument and envelope are dynamic assemblies that orchestrate a sequential series of events that ends with the delivery of the genome into the nucleus...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528438/herpes-simplex-virus-membrane-fusion
#7
Darin J Weed, Anthony V Nicola
Herpes simplex virus mediates multiple distinct fusion events during infection. HSV entry is initiated by fusion of the viral envelope with either the limiting membrane of a host cell endocytic compartment or the plasma membrane. In the infected cell during viral assembly, immature, enveloped HSV particles in the perinuclear space fuse with the outer nuclear membrane in a process termed de-envelopment. A cell infected with some strains of HSV with defined mutations spread to neighboring cells by a fusion event called syncytium formation...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528437/initial-contact-the-first-steps-in-herpesvirus-entry
#8
Walid Azab, Klaus Osterrieder
The entry process of herpesviruses into host cells is complex and highly variable. It involves a sequence of well-orchestrated events that begin with virus attachment to glycan-containing proteinaceous structures on the cell surface. This initial contact tethers virus particles to the cell surface and results in a cascade of molecular interactions, including the tight interaction of viral envelope glycoproteins to specific cell receptors. These interactions trigger intracellular signaling and finally virus penetration after fusion of the viral envelope with cellular membranes...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#9
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28522392/low-molecular-weight-mannogalactofucans-prevent-herpes-simplex-virus-type-1-infection-via-activation-of-toll-like-receptor-2
#10
Woo Jung Kim, Ji Won Choi, Won Jong Jang, Young-Sun Kang, Chang Won Lee, Andriy Synytsya, Yong Il Park
Low-molecular-weight mannogalactofucans (LMMGFs, <4000g/mol) were prepared by the enzymatic degradation of Undaria pinnatifida sporophyll galactofucan (MF) and evaluated or their antiviral activities and underlying action mechanisms against herpes simplex virus type 1 (HSV-1). The 50% inhibitory concentrations (IC50) of LMMGFs and MF were 2.64 and 2.42μg/mL, respectively. LMMGFs inhibited the viral entry on the host cell surface and also exhibited inhibitory activity directly against viral particles, as observed in a virucidal assay...
May 15, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28522322/imaging-macropinosomes-during-shigella-infections
#11
REVIEW
Noelia Lopez-Montero, Yuen-Yan Chang, Anna Sartori-Rupp, Sonja Kühn, Jost Enninga
Macropinocytosis is the uptake of extracellular fluid within vesicles of varying size that takes place during numerous cellular processes in a large variety of cells. A growing number of pathogens, including viruses, parasites, and bacteria are known to induce macropinocytosis during their entry into targeted host cells. We have recently discovered that the human enteroinvasive, bacterial pathogen Shigella causes in situ macropinosome formation during its entry into epithelial cells. These infection-associated macropinosomes are not generated to ingest the bacteria, but are instead involved in Shigella's intracellular niche formation...
May 15, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28521215/adaptation-of-hiv-1-to-cells-with-low-expression-of-the-ccr5-coreceptor
#12
Nicole Espy, Beatriz Pacheco, Joseph Sodroski
The binding of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer ((gp120/gp41)3) to the receptors CD4 and CCR5 triggers virus entry into host cells. To identify Env regions that respond to CCR5 binding, HIV-1 was serially passaged on a CD4-positive canine cell line expressing progressively lower levels of CCR5. HIV-1 replication was observed in cells expressing ~1300 CCR5 molecules/cell. Env changes that conferred this low-CCR5 replication phenotype were located outside of the known CCR5-binding region of the gp120 Env subunit and did not apparently increase CCR5 binding affinity...
May 15, 2017: Virology
https://www.readbyqxmd.com/read/28515293/virus-like-vesicles-of-kaposi-s-sarcoma-associated-herpesvirus-activate-lytic-replication-through-triggering-differentiation-signaling
#13
Danyang Gong, Xinghong Dai, Yuchen Xiao, Yushen Du, Travis J Chapa, Jeffrey R Johnson, Xinmin Li, Nevan J Krogan, Hongyu Deng, Ting-Ting Wu, Ren Sun
Virus-like vesicles (VLVs) are membrane enclosed vesicles that resemble native enveloped viruses in organization, but lack viral capsid and genome. During the productive infection of tumor associated gamma-herpesviruses, both virions and VLVs are produced and released into the extracellular space. However, studies of gamma-herpesvirus associated VLVs have been largely restricted by the technical difficulty of separating VLVs from mature virions. Here, we report a strategy of using a Kaposi's sarcoma-associated herpesvirus (KSHV) mutant defective in small capsid protein, unable to produce mature virions, to selectively isolate VLVs...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28515290/a-point-mutation-in-the-rhesus-rotavirus-vp4-protein-generated-through-rotavirus-reverse-genetics-system-attenuates-the-murine-model-of-biliary-atresia
#14
Sujit K Mohanty, Bryan Donnelly, Phylicia Dupree, Inna Lobeck, Sarah Mowery, Jaroslaw Meller, Monica McNeal, Greg Tiao
Rotavirus infection is one of the most common causes of diarrheal illness in humans. In neonatal mice, rhesus rotavirus (RRV) can induce biliary atresia (BA), a disease resulting in inflammatory obstruction of the extra-hepatic biliary tract and intrahepatic bile ducts. We have previously shown that the amino acid, arginine (R) within the sequence "SRL" (amino acids 445-447) on the RRV VP4 protein is required for viral binding and entry into biliary epithelial cells. To determine if the single amino acid (R) influences the pathogenicity of the virus, we generated a recombinant virus with a single amino acid mutation at this site through a reverse genetics system...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28514853/targeting-the-central-nervous-system-cns-a-review-of-rabies-virus-targeting-strategies
#15
Mira Oswald, Simon Geissler, Achim Goepferich
The transport of drugs across the blood-brain barrier is challenging. The use of peptide sequences derived from viruses with a central nervous system (CNS) tropism is one elegant option. A prominent example is the rabies virus glycopeptide-29 (RVG-29), which is said to enable a targeted brain delivery. Although the entry mechanism of the rabies virus into the CNS is very well characterized, it is unknown whether RVG-29-functionalized drug delivery systems (DDSs) follow this pathway. RVG-29-functionalized DDSs present themselves with modifications of the RVG-29 peptide sequence and different physicochemical properties compared to the rabies virus...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28513596/an-innate-defense-peptide-bpifa1-splunc1-restricts-influenza-a-virus-infection
#16
K M Akram, N A Moyo, G H Leeming, L Bingle, S Jasim, S Hussain, A Schorlemmer, A Kipar, P Digard, R A Tripp, R V Shohet, C D Bingle, J P Stewart
The airway epithelium secretes proteins that function in innate defense against infection. Bactericidal/permeability-increasing fold-containing family member A1 (BPIFA1) is secreted into airways and has a protective role during bacterial infections, but it is not known whether it also has an antiviral role. To determine a role in host defense against influenza A virus (IAV) infection and to find the underlying defense mechanism, we developed transgenic mouse models that are deficient in BPIFA1 and used these, in combination with in vitro three-dimensional mouse tracheal epithelial cell (mTEC) cultures, to investigate its antiviral properties...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28512095/structure-based-mutations-in-the-herpes-simplex-virus-1-glycoprotein-b-ectodomain-arm-impart-a-slow-entry-phenotype
#17
Qing Fan, Sarah J Kopp, Sarah A Connolly, Richard Longnecker
Glycoprotein B (gB) is the conserved herpesvirus fusion protein, and it is required for the entry of herpesviruses. The structure of the postfusion conformation of gB has been solved for several herpesviruses; however, the gB prefusion crystal structure and the details of how the protein refolds from a prefusion to a postfusion form to mediate fusion have not been determined. Using structure-based mutagenesis, we previously reported that three mutations (I671A, H681A, and F683A) in the C-terminal arm of the gB ectodomain greatly reduced cell-cell fusion...
May 16, 2017: MBio
https://www.readbyqxmd.com/read/28512091/conformational-flexibility-in-the-immunoglobulin-like-domain-of-the-hepatitis-c-virus-glycoprotein-e2
#18
Ieva Vasiliauskaite, Ania Owsianka, Patrick England, Abdul Ghafoor Khan, Sarah Cole, Dorothea Bankwitz, Steven K H Foung, Thomas Pietschmann, Joseph Marcotrigiano, Felix A Rey, Arvind H Patel, Thomas Krey
The hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing antibodies and is therefore highly relevant for vaccine design. Its structure features a central immunoglobulin (Ig)-like β-sandwich that contributes to the binding site for the cellular receptor CD81. We show that a synthetic peptide corresponding to a β-strand of this Ig-like domain forms an α-helix in complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of hydrophobic residues and a secondary structure change in the composite CD81 binding site...
May 16, 2017: MBio
https://www.readbyqxmd.com/read/28511927/coordinated-regulation-of-ifitm1-2-and-3-genes-by-an-ifn-responsive-enhancer-through-long-range-chromatin-interactions
#19
Ping Li, Ming-Lei Shi, Wen-Long Shen, Zhang Zhang, De-Jian Xie, Xiang-Yuan Zhang, Chao He, Yan Zhang, Zhi-Hu Zhao
Interferon-induced transmembrane protein (IFITM) 1, 2 and 3 are a family of interferon (IFN)-induced transmembrane proteins that block entry of a broad spectrum of pathogens. However, the transcriptional regulation of these genes, especially whether there exists any enhancers and their roles during the IFN induction process remain elusive. Here, combining episomal luciferase reporter assay and in vivo genome editing, we identified an IFNβ-responsive enhancer located 35kb upstream of IFITM3 gene promoter upregulating the IFNβ-induced expression of IFITM1, 2 and 3 genes, thus contributing to IFNβ-mediated resistance to influenza A virus (IAV) infection...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28501330/virus-entry-and-replication-in-the-brain-precedes-blood-brain-barrier-disruption-during-intranasal-alphavirus-infection
#20
Matthew D Cain, Hamid Salimi, Yongfeng Gong, Lihua Yang, Samantha L Hamilton, James R Heffernan, Jianghui Hou, Mark J Miller, Robyn S Klein
Viral infections of the central nervous system (CNS) are often associated with blood-brain barrier (BBB) disruption, yet the impact of virus replication and immune cell recruitment on BBB integrity are incompletely understood. Using two-photon microscopy, we demonstrate that Venezuelan equine encephalitis virus (VEEV) strain TC83-GFP, a GFP expressing, attenuated strain with a G3A mutation within the 5' UTR that is associated with increased sensitivity to type I interferons (IFNs), does not directly impact BBB permeability...
May 1, 2017: Journal of Neuroimmunology
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