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https://www.readbyqxmd.com/read/28710431/hiv-1-enhances-mtorc1-activity-and-repositions-lysosomes-to-the-periphery-by-co-opting-rag-gtpases
#1
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
#2
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
#3
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
#4
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
#5
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 10, 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
#6
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
#7
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 4, 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
#8
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/delivery-of-chemotherapeutic-vcmmae-using-tobacco-mosaic-virus-nanoparticles
#9
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...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28672171/host-determinants-of-adeno-associated-viral-vector-entry
#10
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 30, 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
#11
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
#12
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
https://www.readbyqxmd.com/read/28659475/a-small-viral-ppxy-peptide-motif-to-control-antiviral-autophagy
#13
Charlotte Montespan, Christopher M Wiethoff, Harald Wodrich
Autophagy is an essential metabolic program also used for clearing intracellular pathogens. This mechanism, also termed selective autophagy, is well characterised for invasive bacteria but remains poorly documented for viral infections. Here we highlight our recent work showing that endosomolytic adenoviruses trigger autophagy when entering cells. Our study revealed how adenoviruses exploit a capsid-associated small PPxY peptide motif to manipulate the autophagic machinery to prevent autophagic degradation and to promote endosomal escape and nuclear trafficking...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28645727/inhibition-of-non-canonical-hiv-1-tat-secretion-through-the-cellular-na-k-atpase-blocks-hiv-1-infection
#14
Silvia Agostini, Hashim Ali, Chiara Vardabasso, Antonio Fittipaldi, Ennio Tasciotti, Anna Cereseto, Antonella Bugatti, Marco Rusnati, Marina Lusic, Mauro Giacca
Besides its essential role in the activation of HIV-1 gene expression, the viral Tat protein has the unusual property of trafficking in and out of cells. In contrast to Tat internalization, the mechanism involved in extracellular Tat release has so far remained elusive. Here we show that Tat secretion occurs through a Golgi-independent pathway requiring binding of Tat with three short, non-consecutive intracytoplasmic loops at the C-terminus of the cellular Na(+),K(+)-ATPase pump alpha subunit. Ouabain, a pump inhibitor, blocked this interaction and prevented Tat secretion; virions produced in the presence of this drug were less infectious, consistent the capacity of virion-associated Tat to increase HIV-1 infectivity...
June 13, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28645309/herpes-simplex-virus-1-infects-the-olfactory-bulb-shortly-following-ocular-infection-and-exhibits-a-long-term-inflammatory-profile-in-the-form-of-effector-and-hsv-1-specific-t-cells
#15
Chandra M Menendez, Daniel J J Carr
BACKGROUND: Herpes simplex virus 1 (HSV-1) infection can result in a life-threatening condition known as herpes simplex encephalitis (HSE). Trafficking patterns by which the virus reaches the central nervous system (CNS) following ocular infection are unresolved. We evaluated early viral dissemination pathways following ocular infection that involve trafficking to the olfactory bulb (OB). Additionally, we have characterized the capacity of HSV-1 to establish latency within OB tissue and profiled the local T lymphocyte response over the course of the acute infection into latency...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28643392/retroviruses-and-microtubule-associated-motor-proteins
#16
REVIEW
Gloria Arriagada
Retroviruses are obligate intracellular parasites of eukaryotic cells. After reverse transcription, the viral DNA contained in the preintegration complex (PIC) is delivered to the nucleus of the host cell, where it integrates. Before reaching the nucleus, the incoming particle and the PIC must travel throughout the cytoplasm. Likewise the newly synthesized viral proteins and viral particles must transit the cytoplasm during exit. The cytoplasm is a crowded environment and simple diffusion is difficult. Therefore, viruses have evolved to utilize the cellular mechanisms of movement through the cytoplasm, where microtubules are the roads, and the ATP dependent motors dynein and kinesin are the vehicles for retrograde and anterograde trafficking...
June 22, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28642743/hiv-1-nef-signaling-in-intestinal-mucosa-epithelium-suggests-the-existence-of-an-active-inter-kingdom-crosstalk-mediated-by-exosomes
#17
REVIEW
Cristina Felli, Olimpia Vincentini, Marco Silano, Andrea Masotti
The human intestinal mucosal surface represents the first defense against pathogens and regulates the immune response through the combination of epithelial cell (EC) functions and immunological factors. ECs act as sensors of luminal stimuli and interact with the immune cells through signal-transduction pathways, thus representing the first barrier that HIV-1 virus encounters during infection. In particular, the HIV-1 Nef protein plays a crucial role in viral invasion and replication. Nef is expressed early during viral infection and interacts with numerous cellular proteins as a scaffold/adaptor...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28640879/dual-targeting-of-a-virus-movement-protein-to-er-and-plasma-membrane-subdomains-is-essential-for-plasmodesmata-localization
#18
Kazuya Ishikawa, Masayoshi Hashimoto, Akira Yusa, Hiroaki Koinuma, Yugo Kitazawa, Osamu Netsu, Yasuyuki Yamaji, Shigetou Namba
Plant virus movement proteins (MPs) localize to plasmodesmata (PD) to facilitate virus cell-to-cell movement. Numerous studies have suggested that MPs use a pathway either through the ER or through the plasma membrane (PM). Furthermore, recent studies reported that ER-PM contact sites and PM microdomains, which are subdomains found in the ER and PM, are involved in virus cell-to-cell movement. However, functional relationship of these subdomains in MP traffic to PD has not been described previously. We demonstrate here the intracellular trafficking of fig mosaic virus MP (MPFMV) using live cell imaging, focusing on its ER-directing signal peptide (SPFMV)...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28635671/rab33b-controls-hepatitis-b-virus-assembly-by-regulating-core-membrane-association-and-nucleocapsid-processing
#19
Christina Bartusch, Tatjana Döring, Reinhild Prange
Many viruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Using RNA interference (RNAi), we demonstrate that the Golgi/autophagosome-associated Rab33B is required for hepatitis B virus (HBV) propagation in hepatoma cell lines. While Rab33B is dispensable for the secretion of HBV subviral envelope particles, its knockdown reduced the virus yield to 20% and inhibited nucleocapsid (NC) formation and/or NC trafficking. The overexpression of a GDP-restricted Rab33B mutant phenocopied the effect of deficit Rab33B, indicating that Rab33B-specific effector proteins may be involved...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28635265/metabolic-oligosaccharide-engineering-with-alkyne-sialic-acids-confers-neuraminidase-resistance-and-inhibits-influenza-reproduction
#20
Torben Heise, Christian Büll, Daniëlle M Beurskens, Emiel Rossing, Marien I de Jonge, Gosse J Adema, Thomas J Boltje, Jeroen D Langereis
Metabolic incorporation of azide- or alkyne-modified sialic acids into the cellular glycosylation pathway enables the study of sialoglycan expression, localization, and trafficking via bioorthogonal chemistry. Herein, we report that such modifications of the sialic acid sugar can have a profound influence on their hydrolysis by neuraminidases (sialidase). Azidoacetyl (Az)-modified sialic acids were prone to neuraminidase cleavage, whereas propargyloxycarbonyl (Poc)-modified sialic acids were largely resistant to cleavage...
June 27, 2017: Bioconjugate Chemistry
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