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https://www.readbyqxmd.com/read/28331097/loss-of-the-human-cytomegalovirus-us16-protein-abrogates-virus-entry-into-endothelial-and-epithelial-cells-by-reducing-the-virion-content-of-the-pentamer
#1
Anna Luganini, Noemi Cavaletto, Stefania Raimondo, Stefano Geuna, Giorgio Gribaudo
The Human Cytomegalovirus (HCMV) US12 gene family encodes a group of predicted seven-transmembrane proteins whose functions have yet to be established. While inactivation of individual US12 members in laboratory strains of HCMV does not affect viral replication in fibroblasts, disruption of the US16 gene in the low-passage TR strain prevents viral growth in endothelial and epithelial cells. In these cells, the US16-null viruses fail to express IE, E, and L viral proteins due to a defect which occurs prior to IE gene expression...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28331092/monkeypox-virus-host-factor-screen-in-haploid-cells-identifies-essential-role-of-garp-complex-in-extracellular-virus-formation
#2
Susan Realegeno, Andreas S Puschnik, Amrita Kumar, Cynthia Goldsmith, Jillybeth Burgado, Suryaprakash Sambhara, Victoria A Olson, Darin Carroll, Inger Damon, Tetsuya Hirata, Taroh Kinoshita, Jan E Carette, Panayampalli Subbian Satheshkumar
Monkeypox virus (MPXV) is a human pathogen that is a member of the Orthopoxvirus genus, which includes Vaccinia virus and Variola virus (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis and glycosylphosphatidylinositol (GPI) - anchor biosynthesis...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28331084/structural-insights-into-emerging-pediatric-pathogens-human-bocaparvoviruses
#3
Mario Mietzsch, Shweta Kailasan, Jamie Garrison, Maria Ilyas, Paul Chipman, Kalle Kantola, Mandy E Janssen, John Spear, Duncan Sousa, Robert McKenna, Kevin Brown, Maria Söderlund-Venermo, Timothy Baker, Mavis Agbandje-McKenna
Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocaviruses 1 (HBoV1) causes severe respiratory infections and HBoV2-4 gastrointestinal infections in young children. Recent reports of life threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms demand the need to study these pathogens on a molecular and structural level for the development of therapeutics. Towards this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to 2...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28323529/altered-expression-of-a-chloroplast-protein-affects-the-outcome-of-virus-and-nematode-infection
#4
Elena Ganusova, J Hollis Rice, Timothy Scott Carlew, Akshita Patel, Emmanuel Perrodin-Njoku, Tarek Hewezi, Tessa M Burch-Smith
The chloroplast-resident RNA helicase ISE2 (INCREASED SIZE EXCLUSION LIMIT 2) can modulate the formation and distribution of plasmodesmata and intercellular trafficking. We have determined that ISE2 expression is induced by viral infection. Therefore the responses of Nicotiana benthamiana plants with varying levels of ISE2 expression to infection by Tobacco mosaic virus (TMV) and Turnip mosaic virus (TuMV) were examined. Surprisingly, increased or decreased ISE2 expression led to faster viral systemic spread and is some cases enhanced systemic necrosis...
March 21, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28315475/evolution-of-the-ability-to-modulate-host-chemokine-networks-via-gene-duplication-in-human-cytomegalovirus-hcmv
#5
Jessica A Scarborough, John R Paul, Juliet V Spencer
Human cytomegalovirus (HCMV) is a widespread pathogen that is particularly skillful at evading immune detection and defense mechanisms, largely due to extensive co-evolution with its host. One aspect of this co-evolution involves the acquisition of virally encoded G protein-coupled receptors (GPCRs) with homology to the chemokine receptor family. GPCRs are the largest family of cell surface proteins, found in organisms from yeast to humans, and they regulate a variety of cellular processes including development, sensory perception, and immune cell trafficking...
March 14, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28302316/defining-nervous-system-susceptibility-during-acute-and-latent-herpes-simplex-virus-1-infection
#6
REVIEW
Chandra M Menendez, Daniel J J Carr
Herpes simplex viruses are neurotropic human pathogens that infect and establish latency in peripheral sensory neurons of the host. Herpes Simplex Virus-1 (HSV-1) readily infects the facial mucosa that can result in the establishment of a latent infection in the sensory neurons of the trigeminal ganglia (TG). From latency, HSV-1 can reactivate and cause peripheral pathology following anterograde trafficking from sensory neurons. Under rare circumstances, HSV-1 can migrate into the central nervous system (CNS) and cause Herpes Simplex Encephalitis (HSE), a devastating disease of the CNS...
March 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28298605/cxcr5-dependent-entry-of-cd8-t-cells-into-rhesus-macaque-b-cell-follicles-achieved-through-t-cell-engineering
#7
Victor I Ayala, Claire Deleage, Matthew T Trivett, Sumiti Jain, Lori V Coren, Matthew W Breed, Joshua A Kramer, James A Thomas, Jacob D Estes, Jeffrey D Lifson, David E Ott
Follicular helper CD4 T cells, TFH, residing in B-cell follicles within secondary lymphoid tissues, are readily infected by AIDS viruses and are a major source of persistent virus despite relative control of viral replication. This persistence is due at least in part to a relative exclusion of effective antiviral CD8 T cells from B-cell follicles. To determine whether CD8 T cells could be engineered to enter B-cell follicles, we genetically modified unselected CD8 T cells to express CXCR5, the chemokine receptor implicated in cellular entry into B-cell follicles...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28295920/importin-%C3%AE-1-targeting-by-hepatitis-c-virus-ns3-4a-protein-restricts-irf3-and-nf-%C3%AE%C2%BAb-signaling-of-ifnb1-antiviral-response
#8
Bridget Gagné, Nicolas Tremblay, Alex Y Park, Martin Baril, Daniel Lamarre
In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon-β (IFNB1) induction. Using a comprehensive microscopy-based high-content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A-interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF-κB p65 upon Sendai virus (SeV) infection...
March 13, 2017: Traffic
https://www.readbyqxmd.com/read/28288652/conserved-residues-within-the-hiv-1-vpu-transmembrane-proximal-hinge-region-modulate-bst2-binding-and-antagonism
#9
Sabelo Lukhele, Éric A Cohen
BACKGROUND: BST2 inhibits HIV-1 release by tethering nascent virions to the surface of infected cells. HIV-1 Vpu overcomes this restriction by removing BST2 from viral budding sites via BST2 intracellular trapping and sequestration, surface downregulation and/or displacement mechanisms. Vpu is composed of a short luminal tail, a transmembrane domain (TMD) and a cytoplasmic hinge region that is followed by two helices. BST2 counteraction relies on the ability of Vpu to physically bind BST2 through TMD interactions and recruit the clathrin-dependent trafficking machinery via a canonical acidic di-leucine signalling motif within the helix-2 of Vpu...
March 14, 2017: Retrovirology
https://www.readbyqxmd.com/read/28273804/domain-4-d4-of-perfringolysin-o-to-visualize-cholesterol-in-cellular-membranes-the-update
#10
REVIEW
Masashi Maekawa
The cellular membrane of eukaryotes consists of phospholipids, sphingolipids, cholesterol and membrane proteins. Among them, cholesterol is crucial for various cellular events (e.g., signaling, viral/bacterial infection, and membrane trafficking) in addition to its essential role as an ingredient of steroid hormones, vitamin D, and bile acids. From a micro-perspective, at the plasma membrane, recent emerging evidence strongly suggests the existence of lipid nanodomains formed with cholesterol and phospholipids (e...
March 3, 2017: Sensors
https://www.readbyqxmd.com/read/28250129/interferon-gamma-prevents-infectious-entry-of-hpv16-via-an-l2-dependent-mechanism
#11
Patricia M Day, Cynthia D Thompson, Douglas R Lowy, John T Schiller
In this study, we report that IFN-γ, but not IFN α, β or λ treatment, dramatically decreased infection of HPV16 pseudovirus (PsV). In a survey of 20 additional HPV and animal papillomavirus type, we found that many, but not all, PsV types were also inhibited by IFN-γ. Microscopic and biochemical analyses of HPV16 PsV determined that the antiviral effect was exerted at the level of endosomal processing of the incoming capsid and depended on the JAK2/STAT1 pathway. In contrast to infection in the absence of IFN-γ, where L1 proteolytic products are produced during endosomal capsid processing and L2/DNA complexes segregate from L1 in the late endosome and travel to the nucleus, IFN-γ treatment led to decreased L1 proteolysis and retention of L2 and the viral genome in the late endosome/lysosome...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28240606/anticancer-kinase-inhibitors-impair-intracellular-viral-trafficking-and-exert-broad-spectrum-antiviral-effects
#12
Elena Bekerman, Gregory Neveu, Ana Shulla, Jennifer Brannan, Szu-Yuan Pu, Stanley Wang, Fei Xiao, Rina Barouch-Bentov, Russell R Bakken, Roberto Mateo, Jennifer Govero, Claude M Nagamine, Michael S Diamond, Steven De Jonghe, Piet Herdewijn, John M Dye, Glenn Randall, Shirit Einav
Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells...
February 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28186704/mesenchymal-stromal-cells-modulate-monocytes-trafficking-in-coxsackievirus-b3-induced-myocarditis
#13
Kapka Miteva, Kathleen Pappritz, Muhammad El-Shafeey, Fengquan Dong, Jochen Ringe, Carsten Tschöpe, Sophie Van Linthout
Mesenchymal stromal cell (MSC) application in Coxsackievirus B3 (CVB3)-induced myocarditis reduces myocardial inflammation and fibrosis, exerts prominent extra-cardiac immunomodulation, and improves heart function. Although the abovementioned findings demonstrate the benefit of MSC application, the mechanism of the MSC immunomodulatory effects leading to a final cardioprotective outcome in viral myocarditis remains poorly understood. Monocytes are known to be a trigger of myocardial tissue inflammation. The present study aims at investigating the direct effect of MSC on the mobilization and trafficking of monocytes to the heart in CVB3-induced myocarditis...
January 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28183815/proteomic-screen-for-cellular-targets-of-the-vaccinia-virus-f10-protein-kinase-reveals-that-phosphorylation-of-mdia-regulates-stress-fiber-formation
#14
Matthew D Greseth, Dominique M Carter, Scott S Terhune, Paula Traktman
Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm of infected cells. While this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. The viral B1 kinase and H1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the F10 kinase. F10 is essential for virion morphogenesis, beginning with the poorly understood process of diversion of membranes from the ER for the purpose of virion membrane biogenesis...
February 9, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28179529/differential-disruption-of-nucleocytoplasmic-trafficking-pathways-by-rhinovirus-2a-proteases
#15
Kelly Watters, Bahar Inankur, Jaye C Gardiner, Jay Warrick, Nathan M Sherer, John Yin, Ann C Palmenberg
The RNA rhinoviruses (RV) encode 2A proteases (2A(pro)) that contribute essential polyprotein processing and host-cell shutoff functions during infection, including the cleavage of Phe/Gly-containing nucleoporin proteins (Nups) within nuclear pore complexes (NPC). Within the 3 RV species, multiple divergent genotypes encode diverse 2A(pro) sequences which act differentially on specific Nups. Since only subsets of Phe/Gly motifs, particularly those within Nup62, Nup98 and Nup153, are recognized by transport receptors (karyopherins) when trafficking large molecular cargos through the NPC, the processing preferences of individual 2A(pro) predict RV genotype-specific targeting of NPC pathways and cargos...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28164464/hydrophobic-domains-of-mouse-polyomavirus-minor-capsid-proteins-promote-membrane-association-and-virus-exit-from-the-er
#16
Sandra Huérfano, Boris Ryabchenko, Hana Španielová, Jitka Forstová
The minor structural protein VP2 and its shorter variant, VP3, of mouse polyomavirus (MPyV) are essential for virus exit from the endoplasmic reticulum (ER) during viral trafficking to the nucleus. Here, we followed the role of putative hydrophobic domains (HD) of the minor proteins in membrane affinity and viral infectivity. We prepared variants of VP2, each mutated to decrease hydrophobicity of one of three predicted hydrophobic domains: VP2-mHD1, VP2-mHD2 or VP2-mHD3 mutated in HD1 (amino acids (aa) 60-101), HD2 (aa 125-165) or HD3 (aa 287-307), respectively...
February 5, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28154412/superresolution-imaging-identifies-that-conventional-trafficking-pathways-are-not-essential-for-endoplasmic-reticulum-to-outer-mitochondrial-membrane-protein-transport
#17
Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K Jaiswal, Anamaris M Colberg-Poley
Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28125599/n-glycosylation-of-the-na-taurocholate-cotransporting-polypeptide-ntcp-determines-its-trafficking-and-stability-and-is-required-for-hepatitis-b-virus-infection
#18
Monique D Appelman, Anindita Chakraborty, Ulrike Protzer, Jane A McKeating, Stan F J van de Graaf
The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT...
2017: PloS One
https://www.readbyqxmd.com/read/28119475/%C3%AE-defensin-hd5-inhibits-human-papillomavirus-16-infection-via-capsid-stabilization-and-redirection-to-the-lysosome
#19
Mayim E Wiens, Jason G Smith
α-Defensins are an important class of abundant innate immune effectors that are potently antiviral against a number of nonenveloped viral pathogens; however, a common mechanism to explain their ability to block infection by these unrelated viruses is lacking. We previously found that human defensin 5 (HD5) blocks a critical host-mediated proteolytic processing step required for human papillomavirus (HPV) infection. Here, we show that bypassing the requirement for this cleavage failed to abrogate HD5 inhibition...
January 24, 2017: MBio
https://www.readbyqxmd.com/read/28119397/misdirection-of-endosomal-trafficking-mediated-by-herpes-simplex-virus-encoded-glycoprotein-b
#20
Naima Niazy, Sebastian Temme, Derya Bocuk, Carmen Giesen, Angelika König, Nadine Temme, Angelique Ziegfeld, Tone F Gregers, Oddmund Bakke, Thorsten Lang, Anna M Eis-Hübinger, Norbert Koch
Herpes simplex virus (HSV)-encoded glycoprotein B (gB) is the most abundant protein in the viral envelope and promotes fusion of the virus with the cellular membrane. In the present study, we found that gB impacts on the major histocompatibility complex (MHC)-II pathway of antigen presentation by fostering homotypic fusion of early endosomes and trapping MHC-II molecules in these altered endosomes. By using an overexpression approach, we demonstrated that transient expression of gB induces giant vesicles of early endosomal origin, which contained Rab5, early endosomal antigen 1 (EEA1), large amounts of MHC-II molecules [human leukocyte antigen (HLA)-DR, and HLA-DM] but no CD63...
January 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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