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Viral trafficking

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https://www.readbyqxmd.com/read/28783704/constitutive-resistance-to-viral-infection-in-human-cd141-dendritic-cells
#1
Aymeric Silvin, Chun I Yu, Xavier Lahaye, Francesco Imperatore, Jean-Baptiste Brault, Sylvain Cardinaud, Christian Becker, Wing-Hong Kwan, Cécile Conrad, Mathieu Maurin, Christel Goudot, Santy Marques-Ladeira, Yuanyuan Wang, Virginia Pascual, Esperanza Anguiano, Randy A Albrecht, Matteo Iannacone, Adolfo García-Sastre, Bruno Goud, Marc Dalod, Arnaud Moris, Miriam Merad, A Karolina Palucka, Nicolas Manel
Dendritic cells (DCs) are critical for the launching of protective T cell immunity in response to viral infection. Viruses can directly infect DCs, thereby compromising their viability and suppressing their ability to activate immune responses. How DC function is maintained in light of this paradox is not understood. By analyzing the susceptibility of primary human DC subsets to viral infections, we report that CD141(+) DCs have an innate resistance to infection by a broad range of enveloped viruses, including HIV and influenza virus...
July 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783139/antipsychotic-induced-hdac2-transcription-via-nf-%C3%AE%C2%BAb-leads-to-synaptic-and-cognitive-side-effects
#2
Daisuke Ibi, Mario de la Fuente Revenga, Nebojsa Kezunovic, Carolina Muguruza, Justin M Saunders, Supriya A Gaitonde, José L Moreno, Maryum K Ijaz, Vishaka Santosh, Alexey Kozlenkov, Terrell Holloway, Jeremy Seto, Aintzane García-Bea, Mitsumasa Kurita, Grace E Mosley, Yan Jiang, Daniel J Christoffel, Luis F Callado, Scott J Russo, Stella Dracheva, Juan F López-Giménez, Yongchao Ge, Carlos R Escalante, J Javier Meana, Schahram Akbarian, George W Huntley, Javier González-Maeso
Antipsychotic drugs remain the standard for schizophrenia treatment. Despite their effectiveness in treating hallucinations and delusions, prolonged exposure to antipsychotic medications leads to cognitive deficits in both schizophrenia patients and animal models. The molecular mechanisms underlying these negative effects on cognition remain to be elucidated. Here we demonstrate that chronic antipsychotic drug exposure increases nuclear translocation of NF-κB in both mouse and human frontal cortex, a trafficking event triggered via 5-HT2A-receptor-dependent downregulation of the NF-κB repressor IκBα...
August 7, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28759649/the-tetraspanin-cd9-facilitates-mers-coronavirus-entry-by-scaffolding-host-cell-receptors-and-proteases
#3
James T Earnest, Michael P Hantak, Kun Li, Paul B McCray, Stanley Perlman, Tom Gallagher
Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28747507/roles-of-cellular-nsf-protein-in-entry-and-nuclear-egress-of-budded-virions-of-autographa-californica-multiple-nucleopolyhedrovirus
#4
Ya Guo, Qi Yue, Jinli Gao, Zhe Wang, Yun-Ru Chen, Gary W Blissard, Tong-Xian Liu, Zhaofei Li
In eukaryotic cells, the soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) proteins comprise the minimal machinery that triggers fusion of transport vesicles with their target membranes. Comparative studies revealed that genes encoding the components of the SNARE system are highly conserved in yeast, insect, and human genomes. Upon infection of insect cells by the virus AcMNPV, the transcript levels of most SNARE genes were initially up-regulated. We found that overexpression of dominant-negative (DN) forms of NSF or knock-down of the expression of NSF, the key regulator of the SNARE system, significantly affected the infectious AcMNPV production...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724767/integrity-of-the-linker-of-nucleoskeleton-and-cytoskeleton-is-required-for-efficient-herpesvirus-nuclear-egress
#5
Barbara G Klupp, Teresa Hellberg, Harald Granzow, Kati Franzke, Beatriz Dominguez Gonzalez, Rose Goodchild, Thomas C Mettenleiter
Herpesvirus capsids assemble in the nucleus while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724764/rab5-and-rab11-are-required-for-clathrin-dependent-endocytosis-of-japanese-encephalitis-virus-in-bhk-21-cells
#6
Chun-Chun Liu, Yun-Na Zhang, Zhao-Yao Li, Jin-Xiu Hou, Jing Zhou, Lin Kan, Bin Zhou, Pu-Yan Chen
During infection Japanese Encephalitis Virus generally enters host cells via receptor-mediated clathrin dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and post-internalization of JEV were analyzed using biochemical inhibitors, RNA interference and dominant negative mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol, but not caveolae or macropinocytosis...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28721844/cd81-large-extracellular-loop-containing-fusion-proteins-with-a-dominant-negative-effect-on-hcv-cell-spread-and-replication
#7
Boyan Grigorov, Jennifer Molle, Eric Rubinstein, Fabien Zoulim, Birke Bartosch
The roles of CD81 in the hepatitis C virus (HCV) life cycle are multiple but remain ill characterized. CD81 is known to interact with the HCV glycoproteins as an attachment factor. It also has an important role in the post-attachment entry process. Its interaction with claudin-1, for example, is vital for viral uptake and trafficking. Furthermore, CD81 and its role in membrane organization and trafficking are thought to play a pivotal role in HCV replication. Some of these functions are particularly limited to human CD81; others can be substituted with CD81 molecules from other species...
July 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28720531/molecular-cloning-and-characterization-of-the-genes-encoding-the-proteins-of-zika-virus
#8
Wangheng Hou, Ruth Cruz-Cosme, Najealicka Armstrong, Lilian Akello Obwolo, Fayuan Wen, Wenhui Hu, Min-Hua Luo, Qiyi Tang
Zika virus (ZIKV) encodes a precursor protein (also called polyprotein) of about 3424 amino acids that is processed by proteases to generate 10 mature proteins and a small peptide. In the present study, we characterized the chemical features, suborganelle distribution and potential function of each protein using Flag-tagged protein expression system. Western blot analysis revealed the molecular weight of the proteins and the polymerization of E, NS1, and NS3 proteins. In addition, we performed multi-labeled fluorescent immunocytochemistry and subcellular fractionation to determine the subcellular localization of these proteins in host cells...
July 15, 2017: Gene
https://www.readbyqxmd.com/read/28710431/hiv-1-enhances-mtorc1-activity-and-repositions-lysosomes-to-the-periphery-by-co-opting-rag-gtpases
#9
Alessandro Cinti, Valerie Le Sage, Miroslav P Milev, Fernando Valiente-Echeverría, Christina Crossie, Marie-Joelle Miron, Nelly Panté, Martin Olivier, Andrew J Mouland
HIV-1 co-opts several host machinery to generate a permissive environment for viral replication and transmission. In this work we reveal how HIV-1 impacts the host translation and intracellular vesicular trafficking machineries for protein synthesis and to impede the physiological late endosome/lysosome (LEL) trafficking in stressful conditions. First, HIV-1 enhances the activity of the master regulator of protein synthesis, the mammalian target of rapamycin (mTOR). Second, the virus commandeers mTOR-associated late endosome/lysosome (LEL) trafficking and counteracts metabolic and environmental stress-induced intracellular repositioning of LEL...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28702009/crm1-inhibitors-for-antiviral-therapy
#10
REVIEW
Cynthia Mathew, Reena Ghildyal
Infectious diseases are a major global concern and despite major advancements in medical research, still cause significant morbidity and mortality. Progress in antiviral therapy is particularly hindered by appearance of mutants capable of overcoming the effects of drugs targeting viral components. Alternatively, development of drugs targeting host proteins essential for completion of viral lifecycle holds potential as a viable strategy for antiviral therapy. Nucleocytoplasmic trafficking pathways in particular are involved in several pathological conditions including cancer and viral infections, where hijacking or alteration of function of key transporter proteins, such as Chromosome Region Maintenance1 (CRM1) is observed...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28696821/multifaceted-role-of-smcr8-as-autophagy-regulator
#11
Jennifer Jung, Christian Behrends
Through autophagy intracellular material is engulfed by double membrane vesicles and delivered to lysosomes for degradation. This process requires Rab GTPases, Rab GAPs and Rab GEFs for proper membrane trafficking, since they control vesicle budding, targeting and fusion. Deregulation of autophagy contributes to several human diseases including cancer, bacterial or viral infections and neurodegeneration. This review focuses on the complex roles of the newly identified protein SMCR8 and its interaction partners during formation and maturation of autophagosomes as well as regulation of lysosomal function and further discusses their implication in neurodegenerative diseases such as ALS and FTD...
July 11, 2017: Small GTPases
https://www.readbyqxmd.com/read/28696820/viral-interactions-with-host-cell-rab-gtpases
#12
Paul Spearman
Viruses are obligate intracellular parasites that utilize cellular machinery for many aspects of their replication cycles. Enveloped viruses generally rely upon host vesicular trafficking machinery to direct their structural proteins and genomes to sites of virus replication, assembly, and budding. Rab GTPases have been implicated in the replication of many important viral pathogens infecting humans. This review provides a summary of virus-Rab protein interactions, with a particular focus on the role of Rab-related trafficking pathways on late events in the lifecycle of herpesviruses and of HIV-1...
July 11, 2017: Small GTPases
https://www.readbyqxmd.com/read/28696309/influenza-infection-triggers-disease-in-a-genetic-model-of-experimental-autoimmune-encephalomyelitis
#13
Stephen Blackmore, Jessica Hernandez, Michal Juda, Emily Ryder, Gregory G Freund, Rodney W Johnson, Andrew J Steelman
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Most MS patients experience periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Interestingly, upper-respiratory viral infections increase the risk for relapse. Here, we used an autoimmune-prone T-cell receptor transgenic mouse (2D2) and a mouse-adapted human influenza virus to test the hypothesis that upper-respiratory viral infection can cause glial activation, promote immune cell trafficking to the CNS, and trigger disease...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28690108/improving-homing-in-t-cell-therapy
#14
Debora Vignali, Marinos Kallikourdis
Cytotoxic T lymphocytes (cytotoxic T cells, CTLs) are an immune effector cell population that can mediate specific immune responses against cancer. Based on this concept, tumor immunotherapy protocols have been developed using adoptive transfer of in vitro-expanded autologous T cells that can kill cancer cells. However, fully functional adoptive T cell therapies (ACT) are hampered by the inability to guarantee that all transferred T cells manage to reach the tumor sites and make contact with cancer cells. The lack of tumor homing of T cells may be caused by a variety of reasons...
June 23, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28687362/the-unexpected-function-of-a-highly-conserved-yxx%C3%AE-motif-in-hcv-core-protein
#15
Eirini Karamichali, Elisavet Serti, Aikaterini Gianneli, Aikaterini Papaefthymiou, Athanassios Kakkanas, Pelagia Foka, Alexandros Seremetakis, Konstantina Katsarou, Ioannis P Trougakos, Urania Georgopoulou
Hepatitis C virus (HCV) is an RNA positive strand virus, member of the Flaviviridae family. The HCV viral particle is composed of a capsid containing the genome, surrounded by an endoplasmic reticulum (ER)-derived lipid bilayer where E1 and E2 are assembled as heterodimers. However, different forms of viral particles have been identified in the serum of HCV-infected patients, including non-enveloped particles. Previous reports have demonstrated that HCV non-enveloped capsid-like particles (HCVne) can be generated by HCV core protein sequence...
July 5, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28683318/analysis-of-iav-replication-and-co-infection-dynamics-by-a-versatile-rna-viral-genome-labeling-method
#16
Dan Dou, Iván Hernández-Neuta, Hao Wang, Henrik Östbye, Xiaoyan Qian, Swantje Thiele, Patricia Resa-Infante, Nancy Mounogou Kouassi, Vicky Sender, Karina Hentrich, Peter Mellroth, Birgitta Henriques-Normark, Gülsah Gabriel, Mats Nilsson, Robert Daniels
Genome delivery to the proper cellular compartment for transcription and replication is a primary goal of viruses. However, methods for analyzing viral genome localization and differentiating genomes with high identity are lacking, making it difficult to investigate entry-related processes and co-examine heterogeneous RNA viral populations. Here, we present an RNA labeling approach for single-cell analysis of RNA viral replication and co-infection dynamics in situ, which uses the versatility of padlock probes...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28675044/featured-article-delivery-of-chemotherapeutic-vcmmae-using-tobacco-mosaic-virus-nanoparticles
#17
Daniel L Kernan, Amy M Wen, Andrzej S Pitek, Nicole F Steinmetz
The first-line treatment for non-Hodgkin's lymphoma is chemotherapy. While generally well tolerated, off-target effects and chemotherapy-associated complications are still of concern. To overcome the challenges associated with systemic chemotherapy, we developed a biology-inspired, nanoparticle drug delivery system (nanoDDS) making use of the nucleoprotein components of the tobacco mosaic virus (TMV). Virus-based nanoparticles, including the high-aspect ratio soft nanorods formed by TMV, are growing in popularity as nanoDDS due to their simple genetic and chemical engineerability, size and shape tunability, and biocompatibility...
August 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28672171/host-determinants-of-adeno-associated-viral-vector-entry
#18
REVIEW
Sirika Pillay, Jan E Carette
Viral vectors based on adeno-associated virus (AAV) are leading candidates for therapeutic gene delivery. Understanding rate-limiting steps in the entry of AAV vectors may be used in a rational approach to improve efficiency and specificity of transduction. This review describes our current understanding of AAV entry, a key step during infection. We discuss the identity and functions of AAV receptors and attachment factors, including the recently discovered multi-serotype receptor AAVR. We further provide an overview of other host factors that act during the trafficking stage of AAV vector transduction...
June 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28669820/bidirectional-factors-impact-the-migration-of-nk-cells-to-draining-lymph-node-in-aged-mice-during-influenza-virus-infection
#19
Xuefeng Duan, Jiao Lu, Haoyu Wang, Xiaofei Liu, Jing Wang, Kai Zhou, Wei Jiang, Yingchun Wang, Min Fang
Natural killer (NK) cells play an important role in controlling several viral diseases. Our previous studies demonstrated an age-dependent susceptibility to mousepox due to defective NK cell responses and trafficking. However, the mechanisms that underlie the age-related impairment in NK cell migration have yet to be identified. In the present study, we demonstrated that after influenza A virus (IAV) infection, NK cells from aged mice (17-19months old) failed to accumulate in draining lymph node (D-LN). We found that both environmental and intrinsic factors played roles for this defect...
June 29, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28666141/computational-design-of-peptide-ligands-to-target-the-intermolecular-interaction-between-viral-envelope-protein-and-pediatric-receptor
#20
Darong Xu, Hongliang Bian, Jinlan Cai, Daocheng Bao, Qing Jin, Min Zhu, Cuifeng Zhang, Tingting Tao
The recognition and binding of viral envelope protein to pediatric receptor subverts the membrane-trafficking apparatus to mediate virion export in young children. Here, we described a successful computational design of peptide ligands to target the intermolecular interaction between the virus large envelope protein (LHB) and adaptin receptor (ADT). Based on the crystal structure of ADT in complex with an oligopeptide segment corresponding to the core binding site of LHB, a sequence-specific amino acid preference profile was determined systematically for the ADT-binding peptides using structural bioinformatics approach...
June 17, 2017: Computational Biology and Chemistry
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