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https://www.readbyqxmd.com/read/28344996/codon-optimization-leads-to-functional-impairment-of-rd114-tr-envelope-glycoprotein
#1
Eleonora Zucchelli, Monika Pema, Anna Stornaiuolo, Claudia Piovan, Cinzia Scavullo, Erica Giuliani, Sergio Bossi, Stefano Corna, Claudia Asperti, Claudio Bordignon, Gian-Paolo Rizzardi, Chiara Bovolenta
Lentiviral vectors (LVs) are a highly valuable tool for gene transfer currently exploited in basic, applied, and clinical studies. Their optimization is therefore very important for the field of vectorology and gene therapy. A key molecule for LV function is the envelope because it guides cell entry. The most commonly used in transiently produced LVs is the vesicular stomatitis virus glycoprotein (VSV-G) envelope, whose continuous expression is, however, toxic for stable LV producer cells. In contrast, the feline endogenous retroviral RD114-TR envelope is suitable for stable LV manufacturing, being well tolerated by producer cells under constitutive expression...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28343331/economic-and-public-health-consequences-of-delayed-access-to-medical-care-for-migrants-living-with-hiv-in-france
#2
Marlène Guillon, Michel Celse, Pierre-Yves Geoffard
In 2013, migrants accounted for 46% of newly diagnosed cases of HIV (human immunodeficiency virus) infection in France. These populations meet with specific obstacles leading to late diagnosis and access to medical care. Delayed access to care (ATC) for HIV-infected migrants reduces their life expectancy and quality of life. Given the reduction of infectivity under antiretroviral (ARV) treatment, delayed ATC for HIV-infected migrants may also hinder the control of the HIV epidemic. The objective of this study is to measure the public health and economic consequences of delayed ATC for migrants living with HIV in France...
March 25, 2017: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
https://www.readbyqxmd.com/read/28341742/ph-regulation-in-early-endosomes-and-interferon-inducible-transmembrane-proteins-control-avian-retrovirus-fusion
#3
Tanay M Desai, Mariana Marin, Caleb Mason, Gregory B Melikyan
Enveloped viruses infect host cells by fusing their membranes with those of the host cell, a process mediated by viral glycoproteins upon binding to cognate host receptors or entering into acidic intracellular compartments. Whereas the effect of receptor density on viral infection has been well studied, the role of cell type-specific factors/processes, such as pH regulation, has not been characterized in sufficient detail. Here, we examined the effects of cell-extrinsic factors (buffer environment) and cell-intrinsic factors (interferon-inducible transmembrane proteins, IFITMs), on the pH regulation in early endosomes and on the efficiency of acid-dependent fusion of the Avian Sarcoma and Leukosis Virus, ASLV, with endosomes...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28338950/non-replicative-rna-recombination-of-an-animal-plus-strand-rna-virus-in-the-absence-of-efficient-translation-of-viral-proteins
#4
Maximiliane Kleine Büning, Denise Meyer, Sophia Austermann-Busch, Gleyder Roman-Sosa, Tillmann Rümenapf, Paul Becher
RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a non-replicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region...
March 11, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28338936/establishment-of-a-human-hepatocellular-cell-line-capable-of-maintaining-long-term-replication-of-hepatitis-b-virus
#5
Wan-Ling Yao, Sotaro Ikeda, Yuta Tsukamoto, Keiko Shindo, Yukie Otakaki, Main Qin, Yoshikazu Iwasawa, Fumihiko Takeuchi, Yuki Kaname, Yu-Chi Chou, Chungming Chang, Koichi Watashi, Takaji Wakita, Takeshi Noda, Hiroki Kato, Takashi Fujita
Hepatitis B virus is a virus whose replication cycle cannot be completely reproduced using cultured cell lines. Here, we report an engineered cell line capable of supporting the complete HBV life cycle. We generated HepG2 cells overexpressing HBV entry receptor human NTCP, and defective in RIG-I-like receptor signaling, by knocking down the IPS-1 adaptor molecule. The resultant NtG20.i7 cells were susceptible to HBV, and its replication was detectable at 14 days post-infection and persisted for at least 35 days with a gradual increase of HBc expression...
March 11, 2017: International Immunology
https://www.readbyqxmd.com/read/28333153/a-novel-inhibitor-idpp-interferes-with-entry-and-egress-of-hcv-by-targeting-glycoprotein-e1-in-a-genotype-specific-manner
#6
Myungeun Lee, Jaewon Yang, Eunji Jo, Ji-Young Lee, Hee-Young Kim, Ralf Bartenschlager, Eui-Cheol Shin, Yong-Soo Bae, Marc P Windisch
Despite recent advances in curing chronic hepatitis C (CHC), the high economic burden to therapy, viral drug resistance, difficult to treat hepatitis C virus (HCV) genotypes and patient groups are still of concern. To address this unmet medical needs, we devised strategies to identify novel viral interventions through target-free high-throughput screening of small molecules utilizing a phenotypic-based HCV infection assay. Thereby, a very potent (EC50 46 ± 26 pM) iminodipyridinopyrimidine (IDPP) drug candidate was selected, and confirmed in primary human hepatocytes (EC50 0...
March 23, 2017: Scientific Reports
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
#7
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/28327617/the-cell-surface-mucin-muc1-limits-the-severity-of-influenza-a-virus-infection
#8
J L McAuley, L Corcilius, H-X Tan, R J Payne, M A McGuckin, L E Brown
Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28327518/myeloid-c-type-lectin-receptors-in-viral-recognition-and-antiviral-immunity
#9
REVIEW
João T Monteiro, Bernd Lepenies
Recognition of viral glycans by pattern recognition receptors (PRRs) in innate immunity contributes to antiviral immune responses. C-type lectin receptors (CLRs) are PRRs capable of sensing glycans present in viral pathogens to activate antiviral immune responses such as phagocytosis, antigen processing and presentation, and subsequent T cell activation. The ability of CLRs to elicit and shape adaptive immunity plays a critical role in the inhibition of viral spread within the host. However, certain viruses exploit CLRs for viral entry into host cells to avoid immune recognition...
March 22, 2017: Viruses
https://www.readbyqxmd.com/read/28327126/characterization-and-mechanisms-of-anti-influenza-virus-metabolites-isolated-from-the-vietnamese-medicinal-plant-polygonum-chinense
#10
Thu Thi Tran, Meehyein Kim, Yejin Jang, Hye Won Lee, Hoa Thi Nguyen, Thanh Ngoc Nguyen, Hae Woong Park, Quang Le Dang, Jin-Cheol Kim
BACKGROUND: Polygonum chinense Linn. is a common medicinal plant in Southeast Asia and has been used in traditional medicine in Vietnam. The plant contains phytochemicals with various biological properties; however, its antiviral effect has not yet been demonstrated. This study was aimed to evaluate the anti-influenza virus activity of crude extracts of P. chinense, to characterize antiviral metabolites therefrom and to investigate their mechanisms of antiviral action. METHODS: The methanol (MeOH) extract and organic solvent layers of P...
March 21, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28326469/hsv-1-interaction-to-3-o-sulfated-heparan-sulfate-in-mouse-derived-drg-explant-and-profiles-of-inflammatory-markers-during-virus-infection
#11
Harsh Sharthiya, Chanmoly Seng, T H Van Kuppevelt, Vaibhav Tiwari, Michele Fornaro
The molecular mechanism of herpes simplex virus (HSV) entry and the associated inflammatory response in the nervous system remain poorly understood. Using mouse-derived ex vivo dorsal root ganglia (DRG) explant model and single cell neurons (SCNs), in this study, we provided a visual evidence for the expression of heparan sulfate (HS) and 3-O-sulfated heparan sulfate (3-OS HS) followed by their interactions with HSV-1 glycoprotein B (gB) and glycoprotein D (gD) during cell entry. Upon heparanase treatment of DRG-derived SCN, a significant inhibition of HSV-1 entry was observed suggesting the involvement of HS role during viral entry...
March 21, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28322598/screening-and-functional-profiling-of-small-molecule-hiv-1-entry-and-fusion-inhibitors
#12
Charline Giroud, Yuhong Du, Mariana Marin, Qui Min, Nathan T Jui, Haian Fu, Gregory B Melikyan
HIV-1 entry and fusion with target cells is an important target for antiviral therapy. However, a few currently approved treatments are not effective as monotherapy due to the emergence of drug resistance. This consideration has fueled efforts to develop new bioavailable inhibitors targeting different steps of the HIV-1 entry process. Here, a high-throughput screen was performed of a large library of 100,000 small molecules for HIV-1 entry/fusion inhibitors, using a direct virus-cell fusion assay in a 384 half-well format...
February 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28321215/ifn-%C3%AE-inhibits-drug-resistant-hiv-infection-of-macrophages
#13
Xu Wang, He Wang, Man-Qing Liu, Jie-Liang Li, Run-Hong Zhou, Yu Zhou, Yi-Zhong Wang, Wang Zhou, Wen-Zhe Ho
Type III interferons (IFN-λs) have been demonstrated to inhibit a number of viruses, including HIV. Here, we further examined the anti-HIV effect of IFN-λs in macrophages. We found that IFN-λs synergistically enhanced anti-HIV activity of antiretrovirals [azidothymidine (AZT), efavirenz, indinavir, and enfuvirtide] in infected macrophages. Importantly, IFN-λs could suppress HIV infection of macrophages with the drug-resistant strains, including AZT-resistant virus (A012) and reverse transcriptase inhibitor-resistant virus (TC49)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28320320/antiviral-activity-of-pha767491-against-human-herpes-simplex-virus-in-vitro-and-in-vivo
#14
Jue Hou, Zili Zhang, Qiang Huang, Jun Yan, Xiaohu Zhang, Xiaoliang Yu, Guihua Tan, Chunfu Zheng, Feng Xu, Sudan He
BACKGROUND: Herpes simplex virus (HSV) is a common human pathogen that causes a variety of diseases, including oral-labial, genital lesions and life-threatening encephalitis. The antiviral nucleoside analogues such as acyclovir are currently used in anti-HSV therapies; however, clinical overuse of these drugs has led to the emergence of drug-resistant viral strains. Hence, there is an urgent need to develop new anti-HSV agents. METHODS: To identify novel anti-HSV-1 compounds, we screened the LOPAC small scale library of 1280 bioactive compounds to identify inhibitors of HSV-1-induced necroptosis...
March 20, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28298605/cxcr5-dependent-entry-of-cd8-t-cells-into-rhesus-macaque-b-cell-follicles-achieved-through-t-cell-engineering
#15
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/28296132/polyvalent-2d-entry-inhibitors-for-pseudorabies-and-african-swine-fever-virus
#16
Benjamin Ziem, Jessica Rahn, Ievgen Donskyi, Kim Silberreis, Luis Cuellar, Jens Dernedde, Günther Keil, Thomas C Mettenleiter, Rainer Haag
African swine fever virus (ASFV) is one of the most dangerous viruses for pigs and is endemic in Africa but recently also spread into the Russian Federation and the Eastern border of the EU. So far there is no vaccine or antiviral drug available to curtail the infection. Thus, control strategies based on novel inhibitors are urgently needed. Another highly relevant virus infection in pigs is Aujeszky's disease caused by the alphaherpesvirus pseudorabies virus (PrV). This article reports the synthesis and biological evaluation of novel extracellular matrix-inspired entry inhibitors based on polyglycerol sulfate-functionalized graphene sheets...
March 15, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28294600/histo-blood-group-antigen-presentation-is-critical-for-binding-of-norovirus-vlp-to-glycosphingolipids-in-model-membranes
#17
Waqas Nasir, Martin Frank, Angelika Kunze, Marta Bally, Francisco Parra, Per-Georg Nyholm, Fredrik Höök, Göran Larson
Virus entry depends on biomolecular recognition at the surface of cell membranes. In the case of glycolipid receptors, these events are expected to be influenced by how the glycan epitope close to the membrane is presented to the virus. This presentation of membrane-associated glycans is more restricted than that of glycans in solution, particularly because of orientational constraints imposed on the glycolipid through its lateral interactions with other membrane lipids and proteins. We have developed and employed a total internal reflection fluorescence microscopy-based binding assay and a scheme for molecular dynamics (MD) membrane simulations to investigate the consequences of various glycan presentation effects...
March 27, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28294501/precise-photoremovable-perturbation-of-a-virus-host-interaction
#18
Sarah B Erickson, Raja Mukherjee, Rachel E Kelemen, Chester J J Wrobel, Xiaofu Cao, Abhishek Chatterjee
Viruses utilize distinct binding interactions with a variety of host factors to gain entry into host cells. A chemical strategy is described to precisely perturb a specific molecular interaction between adeno-associated virus and its host cell, which can be rapidly reversed by light. This strategy enables pausing the virus entry process at a specific stage and then restart it rapidly with a non-invasive stimulus. The ability to synchronize the invading virus population at a discrete step in its entry pathway will be highly valuable for enabling facile experimental characterization of the molecular processes underlying this process...
March 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28292253/the-adeno-associated-virus-a-safe-and-effective-vehicle-for-liver-specific-gene-therapy-of-inherited-and-non-inherited-diseases
#19
Kai Yan Mak, Indu G Rajapaksha, Peter W Angus, Chandana B Herath
The first human adeno-associated virus (AAV) was originally discovered in 1960s as a contaminant of adenovirus stocks preparation and thus it had not been of medical interest. Throughout last three decades AAV has gained popularity to be used in gene therapy, mainly due to its replicative defectiveness and lack of pathogenicity in human. In addition, the ability to mediate a stable and long-term expression in both non-dividing and dividing cells with specific tissue tropism makes AAV as one of the most promising candidates for therapeutic gene transfer to treat many genetic as well as non-genetic disorders...
March 14, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28290554/the-core-protein-of-a-pestivirus-protects-the-incoming-virus-against-ifn-induced-effectors
#20
Christiane Riedel, Benjamin Lamp, Benedikt Hagen, Stanislav Indik, Till Rümenapf
A multitude of viral factors - either inhibiting the induction of the IFN-system or its effectors - have been described to date. However, little is known about the role of structural components of the incoming virus particle in protecting against IFN-induced antiviral factors during or immediately after entry. In this study, we take advantage of the previously reported property of Classical swine fever virus (family Flaviviridae, genus Pestivirus) to tolerate a deletion of the core protein if a compensatory mutation is present in the NS3-helicase-domain (Vp447∆c)...
March 14, 2017: Scientific Reports
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