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https://www.readbyqxmd.com/read/28635613/association-of-the-s267f-variant-on-ntcp-gene-and-treatment-response-to-pegylated-interferon-in-patients-with-chronic-hepatitis-b-a-multicentre-study
#1
Kessarin Thanapirom, Sirinporn Suksawatamnuay, Wattana Sukeepaisarnjaroen, Sombat Treeprasertsuk, Tawesak Tanwandee, Phunchai Charatcharoenwitthaya, Satawat Thongsawat, Apinya Leerapun, Teerha Piratvisuth, Rattana Boonsirichan, Chalermrat Bunchorntavakul, Chaowalit Pattanasirigool, Bubpha Pornthisarn, Supoj Tuntipanichteerakul, Ekawee Sripariwuth, Woramon Jeamsripong, Teeranan Sanpanjit, Yong Poovorawan, Piyawat Komolmit
BACKGROUND: Sodium taurocholate co-transporting polypeptide (NTCP) is a cell receptor for hepatitis B virus (HBV). The S267F variant on the NTCP gene is inversely associated with the chronicity of HBV infection, progression to cirrhosis and hepatocellular carcinoma in East Asian populations. This aim of this study was to determine whether the S267F variant was associated with response to pegylated interferon (Peg-IFN) in patients with chronic HBV infection. METHODS: Two hundred and fifty-seven patients with chronic HBV, treated with Peg-IFN for 48 weeks, were identified from 13 tertiary hospitals included in the hepatitis B database of the Thai Association for the Study of the Liver (THASL)...
June 21, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28634115/delineating-the-roles-of-cellular-and-innate-antiviral-immune-parameters-mediating-ranavirus-susceptibility-using-rainbow-trout-cell-lines
#2
Graeme J Lisser, Nguyen T K Vo, Stephanie J DeWitte-Orr
Frog virus 3 is the type species of the Ranavirus genus and the causative agent of massive mortalities of aquatic species worldwide. A critical step in limiting virus replication, particularly early in infection, is the innate immune response. Presently, little is known regarding what innate immune strategies limit FV3 at the cellular level. To this end, the present study uses two rainbow trout cell lines, RTG-2 and RTgutGC, which demonstrate susceptible and relatively resistant phenotypes to FV3 infection, to elucidate susceptibility factors to FV3...
June 17, 2017: Virus Research
https://www.readbyqxmd.com/read/28631596/cholesterol-25-hydroxylase-acts-as-a-host-restriction-factor-on-pseudorabies-virus-replication
#3
Jiang Wang, Lei Zeng, Li Zhang, Zhen-Zhen Guo, Shao-Fang Lu, Sheng-Li Ming, Guo-Li Li, Bo Wan, Ke-Gong Tian, Guo-Yu Yang, Bei-Bei Chu
Cholesterol 25-hydroxylase (CH25H) catalyses the production of 25-hydroxycholesterol (25HC) from cholesterol by adding a second hydroxyl group at position 25. The aim of this study was to examine the antiviral effect of CH25H on pseudorabies virus (PRV), a swine pathogen that can cause devastating disease and economic losses worldwide. The results showed that porcine ch25h was induced by either interferon or PRV infection. PRV infection of porcine alveolar macrophages (3D4/21 cells) was attenuated by CH25H overexpression and enhanced by silencing of CH25H...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28631595/a-32-kda-viral-attachment-protein-of-lymphocystis-disease-virus-lcdv-specifically-interacts-with-a-27-8-kda-cellular-receptor-from-flounder-paralichthys-olivaceus
#4
Ying Zhong, Chenjie Fei, Xiaoqian Tang, Wenbin Zhan, Xiuzhen Sheng
The 27.8 kDa protein in flounder gill (FG) cells was previously proved to be a receptor specific for lymphocystis disease virus (LCDV) entry and infection. In this paper, a 32 kDa viral attachment protein (VAP) of LCDV specifically binding to the 27.8 kDa receptor (27.8R) was found by far-Western blotting coupled with monoclonal antibodies (MAbs) against 27.8R. The 32 kDa protein was confirmed to be encoded by the open reading frame (ORF) 038 gene in LCDV-C, and predicted to contain a putative transmembrane region, multiple N-myristoylation and glycosylation sites and phosphorylation motifs...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28630320/%C3%AE-20-ifitm2-differentially-restricts-x4-and-r5-hiv-1
#5
Wan-Lin Wu, Christopher Robert Grotefend, Ming-Ting Tsai, Yi-Ling Wang, Vladimir Radic, Hyungjin Eoh, I-Chueh Huang
CCR5 (R5)-tropic, but not CXCR4 (X4)-tropic, HIV-1 is associated with primary HIV-1 infection and transmission. Recent studies have shown that IFN-induced transmembrane (IFITM) proteins, including IFITM1, IFITM2, and IFITM3, restrict a broad range of viruses. Here, we demonstrate that an IFITM2 isoform (Δ20 IFITM2) lacking 20 amino acids at the N terminus differentially restricts X4 and R5 HIV-1. Δ20 IFITM2 suppresses replication of X4 HIV-1 strains by inhibiting their entry. High levels of Δ20 IFITM2 expression could be detected in CD4(+) T cells and in monocytes...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630251/valnoctamide-inhibits-cytomegalovirus-infection-in-developing-brain-and-attenuates-neurobehavioral-dysfunctions-and-brain-abnormalities
#6
Sara Ornaghi, Lawrence S Hsieh, Angélique Bordey, Patrizia Vergani, Michael J Paidas, Anthony N van den Pol
Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antivirals, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes...
June 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28624461/emetine-inhibits-replication-of-rna-and-dna-viruses-without-generating-drug-resistant-virus-variants
#7
Nitin Khandelwal, Yogesh Chander, Thachamvally Riyesh, Krishan Dutt Rawat, Pratibha Saini, Chikkahonnaiah Nishanth, Shalini Sharma, Naresh Jindal, Bhupendra N Tripathi, Sanjay Barua, Naveen Kumar
At a noncytotoxic concentration, emetine was found to inhibit replication of DNA viruses [buffalopoxvirus (BPXV) and bovine herpesvirus 1 (BHV-1)] as well as RNA viruses [peste des petits ruminants virus (PPRV) and Newcastle disease virus (NDV)]. Using the time-of-addition and virus step-specific assays, we showed that emetine treatment resulted in reduced synthesis of viral RNA (PPRV and NDV) and DNA (BPXV and BHV-1) as well as inhibiting viral entry (NDV and BHV-1). In addition, emetine treatment also resulted in decreased synthesis of viral proteins...
June 14, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28622346/flavivirus-and-filovirus-evoprinters-new-alignment-tools-for-the-comparative-analysis-of-viral-evolution
#8
Thomas Brody, Amarendra S Yavatkar, Dong Sun Park, Alexander Kuzin, Jermaine Ross, Ward F Odenwald
BACKGROUND: Flavivirus and Filovirus infections are serious epidemic threats to human populations. Multi-genome comparative analysis of these evolving pathogens affords a view of their essential, conserved sequence elements as well as progressive evolutionary changes. While phylogenetic analysis has yielded important insights, the growing number of available genomic sequences makes comparisons between hundreds of viral strains challenging. We report here a new approach for the comparative analysis of these hemorrhagic fever viruses that can superimpose an unlimited number of one-on-one alignments to identify important features within genomes of interest...
June 16, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28614719/systemic-virus-infections-differentially-modulate-cell-cycle-state-and-functionality-of-long-term-hematopoietic-stem-cells-in%C3%A2-vivo
#9
Christoph Hirche, Theresa Frenz, Simon F Haas, Marius Döring, Katharina Borst, Pia-K Tegtmeyer, Ilija Brizic, Stefan Jordan, Kirsten Keyser, Chintan Chhatbar, Eline Pronk, Shuiping Lin, Martin Messerle, Stipan Jonjic, Christine S Falk, Andreas Trumpp, Marieke A G Essers, Ulrich Kalinke
Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28613837/artificial-off-riboswitches-that-downregulate-internal-ribosome-entry-without-hybridization-switches-in-a-eukaryotic-cell-free-translation-system
#10
Atsushi Ogawa, Hiroki Masuoka, Tsubasa Ota
We constructed novel artificial riboswitches that function in a eukaryotic translation system (wheat germ extract), by rationally implanting an in vitro-selected aptamer into the intergenic internal ribosome entry site (IRES) of Plautia stali intestine virus. These eukaryotic OFF-riboswitches (OFF-eRSs) ligand-dose-dependently downregulate IRES-mediated translation without hybridization switches, which typical riboswitches utilize for gene regulation. The hybridization-switch-free mechanism not only allows for easy design but also requires less energy for regulation, resulting in a higher switching efficiency than hybridization-switch-based OFF-eRSs provide...
June 14, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28607078/retroviral-host-range-extension-is-coupled-with-env-activating-mutations-resulting-in-receptor-independent-entry
#11
Anna Lounková, Jan Kosla, David Přikryl, Kryštof Štafl, Dana Kučerová, Jan Svoboda
The extent of virus transmission among individuals and species is generally determined by the presence of specific membrane-embedded virus receptors required for virus entry. Interaction of the viral envelope glycoprotein (Env) with a specific cellular receptor is the first and crucial step in determining host specificity. Using a well-established retroviral model-avian Rous sarcoma virus (RSV)-we analyzed changes in an RSV variant that had repeatedly been able to infect rodents. By envelope gene (env) sequencing, we identified eight mutations that do not match the already described mutations influencing the host range...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28605637/hepatitis-b-surface-antigen-on-subviral-particles-reduces-the-neutralizing-effect-of-anti-hbs-antibodies-on-hepatitis-b-viral-particles-in-vitro
#12
Gustaf E Rydell, Kasthuri Prakash, Heléne Norder, Magnus Lindh
During hepatitis B virus (HBV) infections subviral particles (SVP) consisting mainly of hepatitis B surface antigen are present at much higher concentration than viral particles (VP) in serum. To investigate reasons for this excess of SVP production, SVP and VP were fractionated on a Nycodenz gradient and analyzed for HBV infection of HepG2-NTCP cells with and without anti-HBs antibodies. Our findings showed that SVP significantly reduced the neutralization of VP by anti-HBs, while SVP had little effect on viral entry, supporting the assumption that SVP serve as decoy facilitating cell-to-cell spread of HBV in the presence of neutralizing antibodies...
June 9, 2017: Virology
https://www.readbyqxmd.com/read/28605171/human-immunodeficiency-virus-care-cascade-among-sub-populations-in-rakai-uganda-an-observational-study
#13
Veena G Billioux, Larry W Chang, Steven J Reynolds, Gertrude Nakigozi, Joseph Ssekasanvu, Mary K Grabowski, Robert Ssekubugu, Fred Nalugoda, Godfrey Kigozi, Joseph Kagaayi, David Serwadda, Ronald H Gray, Maria J Wawer
INTRODUCTION: To assess progress towards the UNAIDS 90-90-90 initiative targets, we examined the HIV care cascade in the population-based Rakai Community Cohort Study (RCCS) in rural Uganda and examined differences between sub-groups. METHODS: Self-reports and clinical records were used to assess the proportion achieving each stage in the cascade. Statistical inference based on a χ(2) test for categorical variables and modified Poisson regression were used to estimate prevalence risk ratios (PRRs) and 95% confidence intervals (CI) for enrolment into care and initiating antiretroviral therapy (ART)...
June 5, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28600536/imipramine-inhibits-chikungunya-virus-replication-in-human-skin-fibroblasts-through-interference-with-intracellular-cholesterol-trafficking
#14
Sineewanlaya Wichit, Rodolphe Hamel, Eric Bernard, Loïc Talignani, Fodé Diop, Pauline Ferraris, Florian Liegeois, Peeraya Ekchariyawat, Natthanej Luplertlop, Pornapat Surasombatpattana, Frédéric Thomas, Andres Merits, Valérie Choumet, Pierre Roques, Hans Yssel, Laurence Briant, Dorothée Missé
Chikungunya virus (CHIKV) is an emerging arbovirus of the Togaviridae family that poses a present worldwide threat to human in the absence of any licensed vaccine or antiviral treatment to control viral infection. Here, we show that compounds interfering with intracellular cholesterol transport have the capacity to inhibit CHIKV replication in human skin fibroblasts, a major viral entry site in the human host. Pretreatment of these cells with the class II cationic amphiphilic compound U18666A, or treatment with the FDA-approved antidepressant drug imipramine resulted in a near total inhibition of viral replication and production at the highest concentration used without any cytotoxic effects...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596575/infectious-pancreatic-necrosis-virus-enters-chse-214-cells-via-macropinocytosis
#15
Jorge Levican, Camila Miranda-Cárdenas, Ricardo Soto-Rifo, Francisco Aguayo, Aldo Gaggero, Oscar León
Infectious pancreatic necrosis virus (IPNV) is a non-enveloped virus belonging to the Birnaviridae family. IPNV produces an acute disease in salmon fingerlings, with high mortality rates and persistent infection in survivors. Although there are reports of IPNV binding to various cells, the viral receptor and entry pathways remain unknown. The aim of this study was to determine the endocytic pathway that allows for IPNV entry. We observed that IPNV stimulated fluid uptake and virus particles co-localysed with the uptake marker dextran in intracellular compartments, suggesting a role for macropinocytosis in viral entry...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28594868/design-of-short-peptides-to-block-btla-hvem-interactions-for-promoting-anticancer-t-cell-responses
#16
Marta Spodzieja, Sławomir Lach, Justyna Iwaszkiewicz, Valérie Cesson, Katarzyna Kalejta, Daniel Olive, Olivier Michielin, Daniel E Speiser, Vincent Zoete, Laurent Derré, Sylwia Rodziewicz-Motowidło
Antibody based immune-checkpoint blockade therapy is a major breakthrough in oncology, leading to clinical benefit for cancer patients. Among the growing family of inhibitory receptors, the B and T lymphocyte attenuator (BTLA), which interacts with herpes virus entry mediator (HVEM), is a promising target for immunotherapy. Indeed, BTLA inhibits T-cell proliferation and cytokine production. The crystal structure of the BTLA/HVEM complex has shown that the HVEM(26-38) fragment is directly involved in protein binding...
2017: PloS One
https://www.readbyqxmd.com/read/28592864/infectious-dnas-derived-from-insect-specific-flavivirus-genomes-enable-identification-of-pre-and-post-entry-host-restrictions-in-vertebrate-cells
#17
Thisun B H Piyasena, Yin X Setoh, Jody Hobson-Peters, Natalee D Newton, Helle Bielefeldt-Ohmann, Breeanna J McLean, Laura J Vet, Alexander A Khromykh, Roy A Hall
Flaviviruses such as West Nile virus (WNV), dengue virus and Zika virus are mosquito-borne pathogens that cause significant human diseases. A novel group of insect-specific flaviviruses (ISFs), which only replicate in mosquitoes, have also been identified. However, little is known about the mechanisms of ISF host restriction. We report the generation of infectious cDNA from two Australian ISFs, Parramatta River virus (PaRV) and Palm Creek virus (PCV). Using circular polymerase extension cloning (CPEC) with a modified OpIE2 insect promoter, infectious cDNA was generated and transfected directly into mosquito cells to produce infectious virus indistinguishable from wild-type virus...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592540/covalent-linkage-of-hiv-1-trimers-to-synthetic-liposomes-elicits-improved-b-cell-and-antibody-responses
#18
Shridhar Bale, Geraldine Goebrecht, Armando Stano, Richard Wilson, Takayuki Ota, Karen Tran, Jidnyasa Ingale, Michael B Zwick, Richard T Wyatt
We have demonstrated that a liposomal array of well-ordered trimers enhances B cell activation, germinal center formation and the elicitation of tier-2 autologous neutralizing antibodies. Previously, we coupled well-ordered cleavage-independent NFL trimer via their C-terminal poly-histidine tails to nickel-lipids integrated into the lipid bilayer. Despite favorable in vivo effects, concern remains over the potentially longer term in vivo instability of non-covalent linkage of the trimers to the liposomes. Accordingly, we tested both cobalt coupling and covalent linkage of the trimers to the liposomes by reengineering the poly-histidine tail to include a free cysteine on each protomer of model BG505 NFL trimers to allow covalent linkage...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28589079/role-of-light-in-the-pathogenesis-of-joint-destruction-in-rheumatoid-arthritis
#19
Afsie Sabokbar, Sara Afrough, David J Mahoney, Yoshinobu Uchihara, Catherine Swales, Nicholas A Athanasou
AIM: To characterise the role of substitutes for receptor-activator nuclear factor kappa-B ligand (RANKL) in rheumatoid arthritis (RA) joint destruction. METHODS: Synovial fluid (SF) macrophages isolated from the knee joint of RA patients were incubated with 25 ng/mL macrophage-colony stimulating factor (M-CSF) and 50 ng/mL LIGHT (lymphotoxin-like, exhibits inducible expression and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) in the presence and absence of 25 ng/mL RANKL and 100 ng/mL osteoprotegerin (OPG) on glass coverslips and dentine slices...
May 20, 2017: World Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28575798/design-and-computational-support-for-the-binding-stability-of-a-new-ccr5-cxcr4-dual-tropic-inhibitor-computational-design-of-a-ccr5-cxcr4-drug
#20
Cooper A Taylor, Bill R Miller, Carol A Parish
The human immunodeficiency virus (HIV) infects healthy human cells by binding to the glycoprotein cluster of differentiation 4 receptors on the surface of helper T-cells, along with either of two chemokine receptors, CC chemokine receptor type 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4). Recently, a pyrazolo-piperdine ligand was synthesized and the corresponding biological data showed good binding to both chemokine receptors, effectively blocking HIV-1 entry. Here, we exhaustively assess the atomistic binding interactions of this compound with both CCR5 and CXCR4, and we find that binding is driven by π-stacking interactions between aromatic rings on the ligand and receptor residues, as well as electrostatic interactions involving the protonated piperidine nitrogen...
February 24, 2017: Journal of Molecular Graphics & Modelling
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