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https://www.readbyqxmd.com/read/28107633/binding-and-proton-blockage-by-amantadine-variants-of-the-influenza-m2wt-and-m2s31n-explained
#1
Christina Tzitzoglaki, Anna K Wright, Kathrin-Maria Freudenberger, Anja Hoffmann, Ian Tietjen, Ioannis Stylianakis, Felix Kolarov, David Fedida, Michaela Schmidtke, Guenter Gauglitz, Timothy A Cross, Antonios Kolocouris
While aminoadamantanes are well-established inhibitors of the influenza A M2 proton channel, the mechanisms by which they are rendered ineffective against M2S31N are unclear. Solid state NMR, isothermal titration calorimetry, electrophysiology, anti-viral assays and molecular dynamics simulations suggest stronger binding interactions for aminoadamantanes to M2WT compared to negligible or weak binding to M2S31N. This is due to reshaping of the M2pore when N31 is present, which in contrast to WT, leads: A) to the loss of the V27 pocket for the adamantyl cage and to a predominant orientation of the ligand's ammonium group toward the N-terminus and, B) to the lack of a helical kink upon ligand binding...
January 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28107471/high-serum-lipopolysaccharide-binding-protein-level-in-chronic-hepatitis-c-viral-infection-is-reduced-by-anti-viral-treatments
#2
Hsiao-Ching Nien, Shih-Jer Hsu, Tung-Hung Su, Po-Jen Yang, Jin-Chuan Sheu, Jin-Town Wang, Lu-Ping Chow, Chi-Ling Chen, Jia-Horng Kao, Wei-Shiung Yang
BACKGROUND: Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus (HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon...
2017: PloS One
https://www.readbyqxmd.com/read/28107341/complex-dynamics-of-virus-spread-from-low-infection-multiplicities-implications-for-the-spread-of-oncolytic-viruses
#3
Ignacio A Rodriguez-Brenes, Andrew Hofacre, Hung Fan, Dominik Wodarz
While virus growth dynamics have been well-characterized in several infections, data are typically collected once the virus population becomes easily detectable. Earlier dynamics, however, remain less understood. We recently reported unusual early dynamics in an experimental system using adenovirus infection of human embryonic kidney (293) cells. Under identical experimental conditions, inoculation at low infection multiplicities resulted in either robust spread, or in limited spread that eventually stalled, with both outcomes occurring with approximately equal frequencies...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28106842/adenoviral-vectors-armed-with-cell-fusion-inducing-proteins-as-anti-cancer-agents
#4
REVIEW
Joshua Del Papa, Robin J Parks
Cancer is a devastating disease that affects millions of patients every year, and causes an enormous economic burden on the health care system and emotional burden on affected families. The first line of defense against solid tumors is usually extraction of the tumor, when possible, by surgical methods. In cases where solid tumors can not be safely removed, chemotherapy is often the first line of treatment. As metastatic cancers often become vigorously resistant to treatments, the development of novel, more potent and selective anti-cancer strategies is of great importance...
January 19, 2017: Viruses
https://www.readbyqxmd.com/read/28106111/broad-range-antiviral-activity-of-hydrogen-sulfide-against-highly-pathogenic-rna-viruses
#5
Nikolay Bazhanov, Olivier Escaffre, Alexander N Freiberg, Roberto P Garofalo, Antonella Casola
Hydrogen sulfide is an important endogenous mediator that has been the focus of intense investigation in the past few years, leading to the discovery of its role in vasoactive, cytoprotective and anti-inflammatory responses. Recently, we made a critical observation that H2S also has a protective role in paramyxovirus infection by modulating inflammatory responses and viral replication. In this study we tested the antiviral and anti-inflammatory activity of the H2S slow-releasing donor GYY4137 on enveloped RNA viruses from Ortho-, Filo-, Flavi- and Bunyavirus families, for which there is no FDA-approved vaccine or therapeutic available, with the exception of influenza...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105854/t-705-favipiravir-suppresses-tumor-necrosis-factor-%C3%AE-production-in-response-to-influenza-virus-infection-a-beneficial-feature-of-t-705-as-an-anti-influenza-drug
#6
T Tanaka, T Kamiyama, T Daikoku, K Takahashi, N Nomura, M Kurokawa, K Shiraki
Influenza virus infection induces the production of various cytokines, which play important roles in the pathogenesis of infection. Among the cytokines induced by influenza, tumor necrosis factor (TNF)-α production has been correlated with the severity of lung lesions. We investigated the effects of T-705 (Favipiravir, 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) on cytokine production due to influenza virus infection in vitro and in vivo, compared with oseltamivir or GS 4071, an active form of oseltamivir. TNF-α production in mouse macrophage-derived P388D1 cells infected with the influenza virus was lower following treatment with T-705 at concentrations of 0...
January 19, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28104138/a2-to-b-blood-type-incompatible-deceased-donor-kidney-transplantation-in-a-recipient-infected-with-the-human-immunodeficiency-virus-a-case-report
#7
R C Forbes, A DeMers, B P Concepcion, D R Moore, H M Schaefer, D Shaffer
BACKGROUND: With the introduction of the Kidney Allocation System in the United States in December 2014, transplant centers can list eligible B blood type recipients for A2 organ offers. There have been no prior reports of ABO incompatible A2 to B deceased donor kidney transplantation in human immunodeficiency virus-positive (HIV+) recipients to guide clinicians on enrolling or performing A2 to B transplantations in HIV+ candidates. We are the first to report a case of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28103773/agaricus-blazei-bioactive-compounds-and-their-effects-on-human-health-benefits-and-controversies
#8
Aline Cristine da Silva de Souza, Vanesa Gesser Correa, Geferson de Almeida Gonçalves, Andréia Assunção Soares, Adelar Bracht, Rosane Marina Peralta
BACKGROUND: The mushroom Agaricus blazei has evoked considerable scientific and practical interest in several fields, especially those linked to its medicinal properties. This review aims to summarize and evaluate the past decade findings related to nutritional and therapeutic uses of A. blazei, with especial emphasis on the most recent discoveries regarding its chemical composition and clinical investigations. METHODS: The specialized literature was searched for basic and clinical studies...
January 18, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28103530/an-anti-oxidant-%C3%AE-lipoic-acid-conjugated-oleoyl-sn-phosphatidylcholineas-a-helper-lipid-in-cationic-liposomal-formulations
#9
Priya Dharmalingam, Balakrishna Marrapu, Chandrashekhar Voshavar, Rasagna Nadella, Vignesh Kumar Rangasami, R V Shaji, Salar Abbas, R B N Prasad, Shiva Shanker Kaki, Srujan Marepally
Development of safe non-viral carrier systems for efficient intra-cellular delivery of drugs and genes hold promise in the area of translational research. Liposome based delivery systems have emerged as one of the attractive strategies for efficient delivery of drugs and nucleic acids. To this end, number of investigations was carried on liposomal formulations using lipids for achieving higher efficiency in transfection with lower cytotoxicities. In our efforts to develop safer and efficient liposomal delivery systems, we synthesized a novel anti-oxidant lipid, α-lipoyl, oleyl-sn-phosphatidylcholine (LOPC) and used as a helper lipid in combination with a cationic amphiphile, Di-Stearyl Dihydroxy Ethyl Ammonium Chloride (DSDEAC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) at varying concentrations of LOPC...
January 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28102839/foot-and-mouth-disease-virus-infection-suppresses-autophagy-and-nf-%C3%B0%C2%BAb-antiviral-responses-via-degradation-of-atg5-atg12-by-3c-pro
#10
Xuxu Fan, Shichong Han, Dan Yan, Yuan Gao, Yanquan Wei, Xiangtao Liu, Ying Liao, Huichen Guo, Shiqi Sun
Autophagy-related protein ATG5-ATG12 is an essential complex for the autophagophore elongation in autophagy, which has been reported to be involved in foot-and-mouth disease virus (FMDV) replication. Previous reports show that ATG5-ATG12 positively or negatively regulates type I interferon (IFN-α/β) pathway during virus infection. In this study, we found that FMDV infection rapidly induced LC3 lipidation and GFP-LC3 subcellular redistribution at the early infection stage in PK-15 cells. Along with infection time course to 2-5 h...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28100833/follicular-cd8-t-cells-accumulate-in-hiv-infection-and-can-kill-infected-cells-in-vitro-via-bispecific-antibodies
#11
Constantinos Petrovas, Sara Ferrando-Martinez, Michael Y Gerner, Joseph P Casazza, Amarendra Pegu, Claire Deleage, Arik Cooper, Jason Hataye, Sarah Andrews, David Ambrozak, Perla M Del Río Estrada, Eli Boritz, Robert Paris, Eirini Moysi, Kristin L Boswell, Ezequiel Ruiz-Mateos, Ilias Vagios, Manuel Leal, Yuria Ablanedo-Terrazas, Amaranta Rivero, Luz Alicia Gonzalez-Hernandez, Adrian B McDermott, Susan Moir, Gustavo Reyes-Terán, Fernando Docobo, Giuseppe Pantaleo, Daniel C Douek, Michael R Betts, Jacob D Estes, Ronald N Germain, John R Mascola, Richard A Koup
Cytolytic CD8 T cells play a crucial role in the control and elimination of virus-infected cells and are a major focus of HIV cure efforts. However, it has been shown that HIV-specific CD8 T cells are infrequently found within germinal centers (GCs), a predominant site of active and latent HIV infection. We demonstrate that HIV infection induces marked changes in the phenotype, frequency, and localization of CD8 T cells within the lymph node (LN). Significantly increased frequencies of CD8 T cells in the B cell follicles and GCs were found in LNs from treated and untreated HIV-infected individuals...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28100782/triphosphate-re-orientation-of-the-incoming-nucleotide-as-a-fidelity-checkpoint-in-viral-rna-dependent-rna-polymerases
#12
Xiaorong Yang, Xinran Liu, Derek M Musser, Ibrahim M Moustafa, Jamie J Arnold, Craig E Cameron, David D Boehr
The nucleotide incorporation fidelity of the viral RNA-dependent RNA polymerase (RdRp) is important for maintaining functional genetic information, but at the same time for generating sufficient genetic diversity to escape the bottlenecks of the host's anti-viral response. We have previously shown that the structural dynamics of the motif-D loop is closely related to nucleotide discrimination. Previous studies have also suggested that there is a re-orientation of the triphosphate of the incoming nucleotide, which is essential prior to nucleophilic attack from the primer RNA 3'-hydroxyl...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100675/protein-synthesis-inhibition-and-gadd34-control-ifn-%C3%AE-heterogeneous-expression-in-response-to%C3%A2-dsrna
#13
Alexandre Dalet, Rafael J Argüello, Alexis Combes, Lionel Spinelli, Sebastien Jaeger, Mathieu Fallet, Thien-Phong Vu Manh, Andreia Mendes, Jessica Perego, Marisa Reverendo, Voahirana Camosseto, Marc Dalod, Tobias Weil, Manuel A Santos, Evelina Gatti, Philippe Pierre
In innate immune responses, induction of type-I interferons (IFNs) prevents virus spreading while viral replication is delayed by protein synthesis inhibition. We asked how cells perform these apparently contradictory activities. Using single fibroblast monitoring by flow cytometry and mathematical modeling, we demonstrate that type-I IFN production is linked to cell's ability to enter dsRNA-activated PKR-dependent translational arrest and then overcome this inhibition by decreasing eIF2α phosphorylation through phosphatase 1c cofactor GADD34 (Ppp1r15a) expression...
January 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28100608/herpes-simplex-virus-type-1-ul24-abrogates-dna-sensing-signal-pathway-by-inhibiting-nf-%C3%AE%C2%BAb-activation
#14
Haiyan Xu, Chenhe Su, Angela Pearson, Christopher H Mody, Chunfu Zheng
: Cyclic GMP-AMP synthase (cGAS) is a newly identified DNA sensor that recognizes foreign DNA, including the genome of herpes simplex virus 1 (HSV-1). Upon binding of viral DNA, cGAS produces cyclic GMP-AMP, which interacts with and activates stimulator of interferon genes (STING) to trigger the transcription of anti-viral genes such as type I interferons and production of inflammatory cytokines. HSV-1 UL24 is widely conserved among the herpesviruses family and is essential for efficient viral replication...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100301/high-throughput-screening-of-a-glaxosmithkline-protein-kinase-inhibitor-set-identifies-an-inhibitor-of-human-cytomegalovirus-replication-that-prevents-creb-and-histone-h3-post-translational-modification
#15
Amina S Khan, Matthew J Murray, Catherine M K Ho, William J Zuercher, Matthew B Reeves, Blair L Strang
To identify new compounds with anti-human cytomegalovirus (HCMV) activity and new anti-HCMV targets, we developed a high throughput strategy to screen a GlaxoSmithKline (GSK) Published Kinase Inhibitor Set (PKIS). This collection contains a range of extensively characterized compounds grouped into chemical families (chemotypes). From our screen we identified compounds within chemotypes that impede HCMV replication and identified kinase proteins associated with inhibition of HCMV replication that are potential novel anti-HCMV targets...
January 18, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28099431/exacerbated-leishmaniasis-caused-by-a-viral-endosymbiont-can-be-prevented-by-immunization-with-its-viral-capsid
#16
Patrik Castiglioni, Mary-Anne Hartley, Matteo Rossi, Florence Prevel, Chantal Desponds, Daniel T Utzschneider, Remzi-Onur Eren, Haroun Zangger, Livia Brunner, Nicolas Collin, Dietmar Zehn, F Matthew Kuhlmann, Stephen M Beverley, Nicolas Fasel, Catherine Ronet
Recent studies have shown that a cytoplasmic virus called Leishmaniavirus (LRV) is present in some Leishmania species and acts as a potent innate immunogen, aggravating lesional inflammation and development in mice. In humans, the presence of LRV in Leishmania guyanensis and in L. braziliensis was significantly correlated with poor treatment response and symptomatic relapse. So far, no clinical effort has used LRV for prophylactic purposes. In this context, we designed an original vaccine strategy that targeted LRV nested in Leishmania parasites to prevent virus-related complications...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28099113/rage-deficiency-predisposes-mice-to-virus-induced-paucigranulocytic-asthma
#17
Jaisy Arikkatt, Md Ashik Ullah, Kirsty Renfree Short, Vivan Zhang, Wan Jun Gan, Zhixuan Loh, Rhiannon B Werder, Jennifer Simpson, Peter D Sly, Stuart B Mazzone, Kirsten M Spann, Manuel Ar Ferreira, John W Upham, Maria B Sukkar, Simon Phipps
Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV)...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28098253/the-clinically-approved-antiviral-drug-sofosbuvir-inhibits-zika-virus-replication
#18
Carolina Q Sacramento, Gabrielle R de Melo, Caroline S de Freitas, Natasha Rocha, Lucas Villas Bôas Hoelz, Milene Miranda, Natalia Fintelman-Rodrigues, Andressa Marttorelli, André C Ferreira, Giselle Barbosa-Lima, Juliana L Abrantes, Yasmine Rangel Vieira, Mônica M Bastos, Eduardo de Mello Volotão, Estevão Portela Nunes, Diogo A Tschoeke, Luciana Leomil, Erick Correia Loiola, Pablo Trindade, Stevens K Rehen, Fernando A Bozza, Patrícia T Bozza, Nubia Boechat, Fabiano L Thompson, Ana M B de Filippis, Karin Brüning, Thiago Moreno L Souza
Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098061/prostate-cancer-immunotherapy-particularly-in-combination-with-androgen-deprivation-or-radiation-treatment-customized-pharmacogenomic-approaches-to-overcome-immunotherapy-cancer-resistance
#19
REVIEW
C Alberti
Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation...
September 2017: Il Giornale di Chirurgia
https://www.readbyqxmd.com/read/28097101/novel-treatment-of-hepatitis-c-virus-infection-for-patients-with-renal-impairment
#20
REVIEW
Goki Suda, Koji Ogawa, Megumi Kimura, Masato Nakai, Takuya Sho, Kenichi Morikawa, Naoya Sakamoto
Prevalence of hepatitis C virus (HCV) infection is high in patients with end-stage renal dysfunction, including patients undergoing hemodialysis (HD). The HCV infection itself can cause glomerulonephritis and puts individuals at increased risk of developing end-stage renal disease; fortunately, successful HCV eradication sometimes restore HCV-related renal dysfunction. Moreover, the prognosis of dialysis patients infected with HCV is significantly worse and the renal allograft survival in HCV-infected patients is also worse than in dialysis patients without HCV infection...
December 28, 2016: Journal of Clinical and Translational Hepatology
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