Publications

biogenesis and transport of membrane domains-potential implications in brain pathologies.	lipids in biological membranes show astonishing chemical diversity, but they also show some key conserved structures in different organisms. in addition, some of their biophysical properties have been related to specific functions. in this review, we aim to discuss the role of sphingolipids- and cholesterol-rich micro- and nano-membrane domains (md) and highlight their pivotal role in lipid-protein clustering processes, vesicle biogenesis and membrane fusion. we further review potential connecti ...	2014	24075975
regulation of pkd1-mediated golgi to cell surface trafficking by gαq subunits.	heterotrimeric gtp-binding proteins play a key role in cell trafficking regulation. above all, specific gβγ subunits have been shown to be a major component of a signal transduction pathway, which also involves phospholipases c (plc), protein kinases c (pkc) and d (pkd), whose main function is to regulate transport between golgi and plasma membrane. it was the involvement of plc which led us to study the role of the other member of this g protein family, the α subunits, in the regulation of memb ...	2014	24175919
preclinical safety and activity of recombinant vsv-ifn-β in an immunocompetent model of squamous cell carcinoma of the head and neck.	recombinant vesicular stomatitis virus expressing interferon-β (vsv-ifn-β) has demonstrated antitumor activity in vitro and in vivo. in preparation for clinical testing in human squamous cell carcinoma (scc) of the head and neck, we conducted preclinical studies of vsv-ifn-β in syngeneic scc models.	2014	24115092
signaling pathways in murine dendritic cells that regulate the response to vesicular stomatitis virus vectors that express flagellin.	vesicular stomatitis virus (vsv) vectors that express heterologous antigens have shown promise as vaccines in preclinical studies. the efficacy of vsv-based vaccines can be improved by engineering vectors that enhance innate immune responses. we previously generated a vsv vaccine vector that incorporates two enhancing strategies: an m protein mutation (m51r) that prevents the virus from suppressing host antiviral responses and a gene encoding bacterial flagellin (m51r-f vector). the rationale wa ...	2014	24198430
the strength of the t cell response against a surrogate tumor antigen induced by oncolytic vsv therapy does not correlate with tumor control.	cancer therapy using oncolytic viruses has gained interest in the last decade. vesicular stomatitis virus is an attractive candidate for this alternative treatment approach. the importance of the immune response against tumor antigens in virotherapy efficacy is now well recognized, however, its relative contribution versus the intrinsic oncolytic capacity of viruses has been difficult to evaluate. to start addressing this question, we compared glycoprotein and matrix mutants of vesicular stomati ...	2014	24590047
implication of pmliv in both intrinsic and innate immunity.	pml/trim19, the organizer of nuclear bodies (nbs), has been implicated in the antiviral response to diverse rna and dna viruses. several pml isoforms generated from a single pml gene by alternative splicing, share the same n-terminal region containing the rbcc/tripartite motif but differ in their c-terminal sequences. recent studies of all the pml isoforms reveal the specific functions of each. the knockout of pml renders mice more sensitive to vesicular stomatitis virus (vsv). here we report th ...	2014	24586174
regulation of mitochondrial antiviral signaling (mavs) expression and signaling by the mitochondria-associated endoplasmic reticulum membrane (mam) protein gp78.	in a previous study, we identified the e3 ubiquitin ligase gp78 by rnai high-throughput screening as a gene whose depletion restricted enterovirus infection. in the current study, we show that gp78, which localizes to the er-mitochondria interface, is a regulator of rig-i-like receptor (rlr) antiviral signaling. we show that depletion of gp78 results in a robust decrease of vesicular stomatitis virus (vsv) infection and a corresponding enhancement of type i interferon (ifn) signaling. mechanisti ...	2014	24285545
newly identified phosphorylation site in the vesicular stomatitis virus p protein is required for viral rna synthesis.	the vesicular stomatitis virus (vsv) rna-dependent rna polymerase consists of two viral proteins; the large (l) protein is the main catalytic subunit, and the phosphoprotein (p) is an essential cofactor for polymerase function. the p protein interacts with the l protein and the n-rna template, thus connecting the polymerase to the template. p protein also binds to free n protein to maintain it in a soluble, encapsidation-competent form. previously, five sites of phosphorylation were identified o ...	2014	24257610
molecular determinants of susceptibility to oncolytic vesicular stomatitis virus in pancreatic adenocarcinoma.	m protein mutant vesicular stomatitis virus (m51r-vsv) has oncolytic properties against many cancers. however, some cancer cells are resistant to m51r-vsv. herein, we evaluate the molecular determinants of vesicular stomatitis virus (vsv) resistance in pancreatic adenocarcinoma cells.	2014	24252853
a single nucleotide polymorphism of porcine mx2 gene provides antiviral activity against vesicular stomatitis virus.	the objective was to determine if single nucleotide polymorphisms (snps) in porcine mx2 gene affect its antiviral potential. mx proteins are known to suppress the multiplication of several viruses, including influenza virus and vesicular stomatitis virus (vsv). in domestic animals possessing highly polymorphic genome, our previous research indicated that a specific snp in chicken mx gene was responsible for its antiviral function. however, there still has been no information about snps in porcin ...	2014	24232602
characterization of ph-sensitive molecular switches that trigger the structural transition of vesicular stomatitis virus glycoprotein from the postfusion state toward the prefusion state.	vesicular stomatitis virus (vsv; the prototype rhabdovirus) fusion is triggered at low ph and mediated by glycoprotein g, which undergoes a low-ph-induced structural transition. a unique feature of rhabdovirus g is that its conformational change is reversible. this allows g to recover its native prefusion state at the viral surface after its transport through the acidic golgi compartments. the crystal structures of g pre- and postfusion states have been elucidated, leading to the identification ...	2014	25210175
sleep and behavior during vesicular stomatitis virus induced encephalitis in balb/cj and c57bl/6j mice.	intranasal application of vesicular stomatitis virus (vsv) produces a well-characterized model of viral encephalitis in mice. within one day post-infection (pi), vsv travels to the olfactory bulb and, over the course of 7 days, it infects regions and tracts extending into the brainstem followed by clearance and recovery in most mice by pi day 14 (pi 14). infectious diseases are commonly accompanied by excessive sleepiness; thus, sleep is considered a component of the acute phase response to infe ...	2014	24055862
switchable aptamers for biosensing and bioseparation of viruses (swaps-v).	there is a widespread interest in the development of aptamer-based affinity chromatographic methods for purification of biomolecules. regardless of the many advantages exhibited by aptamers when compared to other recognition elements, the lack of an efficient regeneration technique that can be generalized to all targets has encumbered further integration of aptamers into affinity-based purification methods. here we offer switchable aptamers (swaps) that have been developed to solve this problem ...	2015	25190090
cd133-targeted gene transfer into long-term repopulating hematopoietic stem cells.	gene therapy for hematological disorders relies on the genetic modification of cd34(+) cells, a heterogeneous cell population containing about 0.01% long-term repopulating cells. here, we show that the lentiviral vector cd133-lv, which uses a surface marker on human primitive hematopoietic stem cells (hscs) as entry receptor, transfers genes preferentially into cells with high engraftment capability. transduction of unstimulated cd34(+) cells with cd133-lv resulted in gene marking of cells with ...	2015	25189742
[mechanism underlying increased expression of a member of the serine/threonine kinase family (citron kinase) induced by hiv-1 infection].	human immunodeficiency virus (hiv)-1 infection changes transcriptional profiles and regulates. the factors and machinery of the host that facilitate viral replication. our previous study suggested that the serine/threonine kinase citron kinase (citk) promotes hiv-1 egress. to ascertain if hiv-1 infection affects citk expression in primary cells, peripheral blood mononuclear cells were infected with vesicular stomatitis virus g protein (vsv-g)-pseudotyped hiv-1 vector nl4-3-luc viruses, which res ...	2015	26524911
march8 inhibits hiv-1 infection by reducing virion incorporation of envelope glycoproteins.	membrane-associated ring-ch 8 (march8) is one of 11 members of the recently discovered march family of ring (really interesting new gene)-finger e3 ubiquitin ligases. march8 downregulates several host transmembrane proteins, including major histocompatibility complex (mhc)-ii, cd86, interleukin (il)-1 receptor accessory protein, tnf-related apoptosis-inducing ligand (trail) receptor 1 and the transferrin receptor. however, its physiological roles remain largely unknown. here we identify march8 a ...	2015	26523972
visualization and quantification of simian immunodeficiency virus-infected cells using non-invasive molecular imaging.	in vivo imaging can provide real-time information and three-dimensional (3d) non-invasive images of deep tissues and organs, including the brain, whilst allowing longitudinal observation of the same animals, thus eliminating potential variation between subjects. current in vivo imaging technologies, such as magnetic resonance imaging (mri), positron emission tomography-computed tomography (pet-ct) and bioluminescence imaging (bli), can be used to pinpoint the spatial location of target cells, wh ...	2015	26297664
first-in-human evaluation of the safety and immunogenicity of a recombinant vesicular stomatitis virus human immunodeficiency virus-1 gag vaccine (hvtn 090).	background. we report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rvsv) human immunodeficiency virus (hiv)-1 vaccine. methods. sixty healthy, hiv-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation study. groups of 12 participants received rvsv hiv-1 gag vaccine at 5 dose levels (4.6 × 10(3) to 3.4 × 10(7) particle forming units) (n = 10/group) or ...	2015	26199949
samhd1 limits hiv-1 antigen presentation by monocyte-derived dendritic cells.	monocyte-derived dendritic cells (mddc) stimulate cd8 cytotoxic t lymphocytes (ctl) by presenting endogenous and exogenous viral peptides via major histocompatibility complex class i (mhc-i) molecules. mddc are poorly susceptible to hiv-1, in part due to the presence of samhd1, a cellular enzyme that depletes intracellular deoxynucleoside triphosphates (dntps) and degrades viral rna. vpx, an hiv-2/sivsm protein absent from hiv-1, antagonizes samhd1 by inducing its degradation. the impact of samh ...	2015	25926647
a single-loop recombinant pseudotyped-virus-based assay to detect hiv-1 phenotypic resistance.	hiv/aids is a leading public health concern throughout the world. currently, treatment of hiv/aids still depends on highly active antiretroviral therapy (haart); however, there is increasing evidence showing the emergence of resistance to antiretroviral drugs in hiv-1 strains, making art less effective over time. intensive monitoring of hiv-1 drug resistance is therefore of great importance to evaluate the current sensitivity of antiretroviral agents and is urgently needed. the aim of this study ...	2015	25795166
increased levels of macrophage inflammatory proteins result in resistance to r5-tropic hiv-1 in a subset of elite controllers.	elite controllers (ecs) are a rare group of hiv seropositive individuals who are able to control viral replication without antiretroviral therapy. the mechanisms responsible for this phenotype, however, have not been fully elucidated. in this study, we examined cd4(+) t cell resistance to hiv in a cohort of elite controllers and explored transcriptional signatures associated with cellular resistance. we demonstrate that a subgroup of elite controllers possess cd4(+) t cells that are specifically ...	2015	25740989
anti-apobec3g activity of hiv-1 vif protein is attenuated in elite controllers.	hiv-1-infected individuals who control viremia to below the limit of detection without antiviral therapy have been termed elite controllers (ec). functional attenuation of some hiv-1 proteins has been reported in ec. the hiv-1 accessory protein vif (virion infectivity factor) enhances viral infectivity through anti-retroviral factor apolipoprotein b mrna editing enzyme catalytic polypeptide-like 3g (apobec3g) degradation; however, little is known regarding vif function in ec. here, the anti-apob ...	2015	25717111
toward the development of a single-round infection assay based on egfp reporting for anti-hiv-1 drug discovery.	the rapid increase of hiv-1 strains resistant to current antiretroviral drugs is a challenge for successful aids therapy. this necessitates the development of novel drugs, and to this end, availability of screening systems for in vitro drug discovery is a priority. herein, we report the modification of a previously developed system for increased sensitivity, ease of use, and cost-efficiency, based on the application of the egfp marker.	2015	26989744
in vitro evaluation of the antiviral properties of shilajit and investigation of its mechanisms of action.	shilajit, a herbomineral substance exuded from rocks in steep mountainous regions, has been used for thousands of years by the indian ayurvedic and siddha systems of traditional medicine to relieve ailments and enhance quality of life. although a large number of therapeutic properties have been ascribed to shilajit, its therapeutic potential is still largely unexplored by modern research and many of its claimed bioactivities lack scientific validation. the present study was undertaken to investi ...	2015	25792012
pet imaging of oncolytic vsv expressing the mutant hsv-1 thymidine kinase transgene in a preclinical hcc rat model.	hepatocellular carcinoma (hcc) is the most predominant form of liver cancer and the third leading cause of cancer-related death worldwide. due to the relative ineffectiveness of conventional hcc therapies, oncolytic viruses have emerged as novel alternative treatment agents. our previous studies have demonstrated significant prolongation of survival in advanced hcc in rats after oncolytic vesicular stomatitis virus (vsv) treatment. in this study, we aimed to establish a reporter system to reliab ...	2015	25609160
the ex vivo purge of cancer cells using oncolytic viruses: recent advances and clinical implications.	hematological malignancies are treated with intensive high-dose chemotherapy, with or without radiation. this is followed by hematopoietic stem cell (hsc) transplantation (hsct) to rescue or reconstitute hematopoiesis damaged by the anticancer therapy. autologous hsc grafts may contain cancer cells and purging could further improve treatment outcomes. similarly, allogeneic hsct may be improved by selectively purging alloreactive effector cells from the graft rather than wholesale immune cell dep ...	2015	27512666
identification of newly emerging influenza viruses by surface-enhanced raman spectroscopy.	in this work, we demonstrate in situ virus identification based on surface-enhanced raman scattering (sers). we hypothesized that newly emerging influenza viruses possess surface proteins and lipids that can generate distinctive raman signals. to test this hypothesis, sers signals were measured from the surface of a noninfluenza virus, two different influenza viruses, and a genetically shuffled influenza virus. to ensure the safety for experimenters we constructed nonreplicating pseudotyped viru ...	2015	26528878
antiviral effects of novel herbal medicine kiom-c, on diverse viruses.	in order to identify new potential antiviral agents, recent studies have advocated thorough testing of herbal medicines or natural substances that are traditionally used to prevent viral infections. antiviral activities and the mechanism of action of the total aqueous extract preparation of kiom-c, a novel herbal medicine, against diverse types of viruses were investigated. in vitro antiviral activity against a/puerto rico/8/34 (h1n1) (pr8), vesicular stomatitis virus (vsv), and newcastle diseas ...	2015	25942440
mapk phosphatase 5 expression induced by influenza and other rna virus infection negatively regulates irf3 activation and type i interferon response.	the type i interferon system is essential for antiviral immune response and is a primary target of viral immune evasion strategies. here, we show that virus infection induces the expression of mapk phosphatase 5 (mkp5), a dual-specificity phosphatase (dusp), in host cells. mice deficient in mkp5 were resistant to h1n1 influenza infection, which is associated with increased irf3 activation and type i interferon expression in comparison with wt mice. increased type i interferon responses were also ...	2015	25772359
epimedium koreanum nakai displays broad spectrum of antiviral activity in vitro and in vivo by inducing cellular antiviral state.	epimedium koreanum nakai has been extensively used in traditional korean and chinese medicine to treat a variety of diseases. despite the plant's known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. in this study, the broad antiviral spectrum and mode of action of an aqueous extract from epimedium koreanum nakai was evaluated in vitro, and moreover, the protective effect against diverg ...	2015	25609307
a viable recombinant rhabdovirus lacking its glycoprotein gene and expressing influenza virus hemagglutinin and neuraminidase is a potent influenza vaccine.	the emergence of novel influenza viruses that cause devastating human disease is an ongoing threat and serves as an impetus for the continued development of novel approaches to influenza vaccines. influenza vaccine development has traditionally focused on producing humoral and/or cell-mediated immunity, often against the viral surface glycoproteins hemagglutinin (ha) and neuraminidase (na). here, we describe a new vaccine candidate that utilizes a replication-defective vesicular stomatitis virus ...	2015	25540378
identification of cellular microrna-136 as a dual regulator of rig-i-mediated innate immunity that antagonizes h5n1 iav replication in a549 cells.	h5n1 influenza a virus (iav) causes severe respiratory diseases and high mortality rates in animals and humans. micrornas are being increasingly studied to evaluate their potential as therapeutic entities to combat viral infection. however, mechanistic studies delineating the roles of micrornas in regulating host-h5n1 virus interactions remain scarce. here, we performed microrna microarray analysis using a549 human lung epithelial cells infected with a highly pathogenic avian influenza virus. th ...	2015	26450567
evidence for a novel mechanism of influenza virus-induced type i interferon expression by a defective rna-encoded protein.	influenza a virus (iav) defective rnas are generated as byproducts of error-prone viral rna replication. they are commonly derived from the larger segments of the viral genome and harbor deletions of various sizes resulting in the generation of replication incompatible viral particles. furthermore, small subgenomic rnas are known to be strong inducers of pattern recognition receptor rig-i-dependent type i interferon (ifn) responses. the present study identifies a novel iav-induced defective rna ...	2015	26024522
effects of different doses of nucleocapsid protein from hantaan virus a9 strain on regulation of interferon signaling.	hantaan virus a9 strain (htnv a9) is an etiologic agent of hemorrhagic fever with renal syndrome in china. the virulence of the pathogenic hantaviruses is determined by their ability to alter key signaling pathways of early interferon (ifn) induction within cells. the potential role of htnv a9 structural proteins, such as nucleocapsid (n) and envelope glycoproteins (gn and gc), in regulating human's innate antiviral immune response has not yet been clarified. in this study, we investigated the e ...	2015	26196448
rhabdovirus-based vaccine platforms against henipaviruses.	the emerging zoonotic pathogens hendra virus (hev) and nipah virus (niv) are in the genus henipavirus in the family paramyxoviridae. hev and niv infections can be highly fatal to humans and livestock. the goal of this study was to develop candidate vaccines against henipaviruses utilizing two well-established rhabdoviral vaccine vector platforms, recombinant rabies virus (rabv) and recombinant vesicular stomatitis virus (vsv), expressing either the codon-optimized or the wild-type (wt) hev glyco ...	2015	25320306
rhodiola rosea exerts antiviral activity in athletes following a competitive marathon race.	rhodiola rosea, a medicinal plant with demonstrated adaptogenic properties, has recently been reported to contain active compounds with antimicrobial activity. the goal of this study was to measure the antiviral and antibacterial properties of the bioactive metabolites of rhodiola rosea in the serum of experienced marathon runners following supplementation. marathon runners, randomly divided into two groups, ingested 600 mg/day of rhodiola rosea (n = 24, 6 female, 18 male) or placebo (n = 24, 7 ...	2015	26284250
recoding of the vesicular stomatitis virus l gene by computer-aided design provides a live, attenuated vaccine candidate.	codon pair bias (cpb), which has been observed in all organisms, is a neglected genomic phenomenon that affects gene expression. cpb results from synonymous codons that are paired more or less frequently in orfeomes regardless of codon bias. the effect of an individual codon pair change is usually small, but when it is amplified by large-scale genome recoding, strikingly altered biological phenotypes are observed. the utility of codon pair bias in the development of live attenuated vaccines was ...	2015	25827413
safety of recombinant vsv-ebola virus vaccine vector in pigs.	the ongoing ebola outbreak in west africa has resulted in fast-track development of vaccine candidates. we tested a vesicular stomatitis virus vector expressing ebola virus glycoprotein for safety in pigs. inoculation did not cause disease and vaccine virus shedding was minimal, which indicated that the vaccine virus does not pose a risk of dissemination in pigs.	2015	25811738
next-generation sequencing reveals a controlled immune response to zaire ebola virus challenge in cynomolgus macaques immunized with vesicular stomatitis virus expressing zaire ebola virus glycoprotein (vsvδg/ebovgp).	vesicular stomatitis virus expressing zaire ebola virus (ebov) glycoprotein (vsvδg/ebovgp) could be used as a vaccine to meet the 2014 ebola virus outbreak. to characterize the host response to this vaccine, we used mrna sequencing to analyze peripheral blood mononuclear cells (pbmcs) from cynomolgus macaques after vsvδg/ebovgp immunization and subsequent ebov challenge. we found a controlled transcriptional response that transitioned to immune regulation as the ebov was cleared. this observatio ...	2015	25589554
ebola virus (ebov) infection: therapeutic strategies.	within less than a year after its epidemic started (in december 2013) in guinea, ebola virus (ebov), a member of the filoviridae, has spread over a number of west-african countries (guinea, sierra leone and liberia) and gained allures that have been unprecedented except by human immunodeficiency virus (hiv). although ebov is highly contagious and transmitted by direct contact with body fluids, it could be counteracted by the adequate chemoprophylactic and -therapeutic interventions: vaccines, an ...	2015	25481298
potential and emerging treatment options for ebola virus disease.	to describe the current ebola virus epidemic and the potential options for treatment and prevention of ebola virus disease.	2015	25414384
clinical development of ebola vaccines.	the ongoing outbreak of ebola virus disease in west africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of ebola vaccines. a number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. these vaccines include dna ...	2015	26668751
human polyclonal antibodies produced through dna vaccination of transchromosomal cattle provide mice with post-exposure protection against lethal zaire and sudan ebolaviruses.	dna vaccination of transchromosomal bovines (tcbs) with dna vaccines expressing the codon-optimized (co) glycoprotein (gp) genes of ebola virus (ebov) and sudan virus (sudv) produce fully human polyclonal antibodies (pabs) that recognize both viruses and demonstrate robust neutralizing activity. each tcb was vaccinated by intramuscular electroporation (im-ep) a total of four times and at each administration received 10 mg of the ebov-gpco dna vaccine and 10 mg of the sudv-gpco dna vaccine at two ...	2015	26422247
dna-directed antibody immobilization for enhanced detection of single viral pathogens.	here, we describe the use of dna-conjugated antibodies for rapid and sensitive detection of whole viruses using a single-particle interferometric reflectance imaging sensor (sp-iris), a simple, label-free biosensor capable of imaging individual nanoparticles. first, we characterize the elevation of the antibodies conjugated to a dna sequence on a three-dimensional (3-d) polymeric surface using a fluorescence axial localization technique, spectral self-interference fluorescence microscopy (ssfm). ...	2015	26378807
ebola vaccine. vsv-ebov rapidly protects macaques against infection with the 2014/15 ebola virus outbreak strain.	the latest ebola virus (ebov) epidemic spread rapidly through guinea, sierra leone, and liberia, creating a global public health crisis and accelerating the assessment of experimental therapeutics and vaccines in clinical trials. one of those vaccines is based on recombinant vesicular stomatitis virus expressing the ebov glycoprotein (vsv-ebov), a live-attenuated vector with marked preclinical efficacy. here, we provide the preclinical proof that vsv-ebov completely protects macaques against let ...	2015	26249231
efficacy and effectiveness of an rvsv-vectored vaccine expressing ebola surface glycoprotein: interim results from the guinea ring vaccination cluster-randomised trial.	a recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of zaire ebolavirus (rvsv-zebov) is a promising ebola vaccine candidate. we report the results of an interim analysis of a trial of rvsv-zebov in guinea, west africa.	2015	26248676
the effect of dose on the safety and immunogenicity of the vsv ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial.	safe and effective vaccines against ebola could prevent or control outbreaks. the safe use of replication-competent vaccines requires a careful dose-selection process. we report the first safety and immunogenicity results in volunteers receiving 3 × 10(5) plaque-forming units (pfu) of the recombinant vesicular stomatitis virus-based candidate vaccine expressing the zaire ebola virus glycoprotein (rvsv-zebov; low-dose vaccinees) compared with 59 volunteers who had received 1 ×10(7) pfu (n=35) or ...	2015	26248510
vaccination with a highly attenuated recombinant vesicular stomatitis virus vector protects against challenge with a lethal dose of ebola virus.	previously, recombinant vesicular stomatitis virus (rvsv) pseudotypes expressing ebolavirus glycoproteins (gps) in place of the vsv g protein demonstrated protection of nonhuman primates from lethal homologous ebolavirus challenge. those pseudotype vectors contained no additional attenuating mutations in the rvsv genome. here we describe rvsv vectors containing a full complement of vsv genes and expressing the ebola virus (ebov) gp from an additional transcription unit. these rvsv vectors contai ...	2015	26109675
characterization of a bivalent vaccine capable of inducing protection against both ebola and cross-clade h5n1 influenza in mice.	ebola virus (ebov) is a lethal pathogen that causes up to 90% mortality in humans, whereas h5n1 avian influenza has a 60% fatality rate. both viruses are considered pandemic threats. the objective was to evaluate the protective efficacy of a bivalent, recombinant vesicular stomatitis virus vaccine expressing both the a/hanoi/30408/2005 h5n1 hemagglutinin and the ebov glycoprotein (vsvδg-ha-zgp) in a lethal mouse model of infection.	2015	26022441
a single-vector, single-injection trivalent filovirus vaccine: proof of concept study in outbred guinea pigs.	the filoviruses, marburg marburgvirus (marv), zaire ebolavirus (zebov), and sudan ebolavirus (sebov), cause severe and often fatal hemorrhagic fever in humans and nonhuman primates (nhps). monovalent recombinant vesicular stomatitis virus (rvsv)-based vaccine vectors, which encode a filovirus glycoprotein (gp) in place of the vsv glycoprotein, have shown 100% efficacy against homologous filovirus challenge in rodent and nhp studies. here, we examined the utility of a single-vector, single-inject ...	2015	25957964
state-of-the-art workshops on medical countermeasures potentially available for human use following accidental exposures to ebola virus.	the ongoing outbreak of ebola in west africa has raised a general awareness that at present there are no ebola-specific medical countermeasures (mcms) with proven effectiveness. this paper recapitulates discussions held at the 6th international filovirus symposium in march 2014 as well as the subsequent design of a randomized clinical trial design for treating ebola virus-infected patients evacuated from west africa to the united states. a number of different drugs or biologics were critically r ...	2015	25957962
amiodarone and metabolite mdea inhibit ebola virus infection by interfering with the viral entry process.	ebola virus disease (evd) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. in the present work, we investigated how amiodarone interferes with ebola virus infection. wild-type sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the zaire ebolavirus glycoprot ...	2015	25933611
lassa-vesicular stomatitis chimeric virus safely destroys brain tumors.	high-grade tumors in the brain are among the deadliest of cancers. here, we took a promising oncolytic virus, vesicular stomatitis virus (vsv), and tested the hypothesis that the neurotoxicity associated with the virus could be eliminated without blocking its oncolytic potential in the brain by replacing the neurotropic vsv glycoprotein with the glycoprotein from one of five different viruses, including ebola virus, marburg virus, lymphocytic choriomeningitis virus (lcmv), rabies virus, and lass ...	2015	25878115
single-dose attenuated vesiculovax vaccines protect primates against ebola makona virus.	the family filoviridae contains three genera, ebolavirus (ebov), marburg virus, and cuevavirus. some members of the ebov genus, including zaire ebolavirus (zebov), can cause lethal haemorrhagic fever in humans. during 2014 an unprecedented zebov outbreak occurred in west africa and is still ongoing, resulting in over 10,000 deaths, and causing global concern of uncontrolled disease. to meet this challenge a rapid-acting vaccine is needed. many vaccine approaches have shown promise in being able ...	2015	25853476
development of an infectious surrogate hepatitis c virus based on a recombinant vesicular stomatitis virus expressing hepatitis c virus envelope glycoproteins and green fluorescent protein.	to develop surrogate viruses for hepatitis c virus (hcv), we previously produced recombinant vesicular stomatitis viruses (rvsvs) lacking glycoprotein g but instead expressing chimeric hcv e1/e2 fused to g. these rvsvs were not infectious in hcv-susceptible hepatoma cells. in this study, to develop an infectious surrogate hcv based on an rvsv (vesicular stomatitis virus [vsv]/hcv), we generated a novel rvsv encoding the native e1/e2 (h77 strain) and green fluorescent protein (gfp) instead of g. ...	2015	25672345
human cytokinome analysis for interferon response.	cytokines are a group of small secreted proteins that mediate a diverse range of immune and nonimmune responses to inflammatory and microbial stimuli. only a few of these cytokines mount an antiviral response, including type i, ii, and iii interferons (ifns). during viral infections and under inflammatory conditions, a number of cytokines and chemokines are coproduced with ifn; however, no systematic study exists on the interactions of the cytokine repertoire with the ifn response. here, we perf ...	2015	25926649
inactivation of viruses in platelet and plasma products using a riboflavin-and-uv-based photochemical treatment.	multilayered blood safety programs reduce the risk of transfusion-transmitted diseases; however, there remains a risk of window period transmission of screened viruses and transmission of unscreened and emerging viruses from asymptomatic donors. to reduce this risk, a riboflavin-and-uv-light-based pathogen reduction process was evaluated against eight viral agents.	2015	25731607
picornavirus rna polyadenylation by 3d(pol), the viral rna-dependent rna polymerase.	poly(a) tails are functionally important features of all picornavirus rna genomes. some viruses have genomes with relatively short poly(a) tails (encephalomyocarditis virus) whereas others have genomes with longer poly(a) tails (polioviruses and rhinoviruses). here we review the polyadenylation of picornavirus rna as it relates to the structure and function of 3d(pol). poliovirus 3d(pol) uses template-dependent reiterative transcription mechanisms as it replicates the poly(a) tails of viral rna ...	2015	25559071
preparation of vesicular stomatitis virus pseudotype with chikungunya virus envelope protein.	chikungunya virus (chikv) is a mosquito-transmitted alphavirus that causes chikungunya fever (chikf) in millions of people mainly in developing countries. chikf is characterized by high fever, fatigue, headache, nausea, vomiting, rash, myalgia and severe arthralgia. to date, there is no specific treatment and no licensed vaccine against chikv infection. in this study, we developed a safe, efficient and easy neutralization assay of chikv based on vesicular stomatitis virus (vsv) pseudotype with c ...	2015	26104337
the olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.	the olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (cns). each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. viruses that can use the olfactory nerve as a shortcut into the cns include influenza a virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatit ...	2015	25294743
ebolavirus vaccines: progress in the fight against ebola virus disease.	ebolaviruses are highly infectious pathogens that cause lethal ebola virus disease (evd) in humans and non-human primates (nhps). due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. in this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vacc ...	2015	26535889
cytomegalovirus-based vaccine expressing a modified tumor antigen induces potent tumor-specific cd8(+) t-cell response and protects mice from melanoma.	the presence of tumor-infiltrating cd8(+) t cells is associated with tumor regression and better prognosis. cytomegalovirus (cmv) infection elicits a robust and long-lasting cd8(+) t-cell response, which makes cmv a potentially promising vaccine vector against cancer. in the current study, we used recombinant murine cmv (mcmv) strains as prophylactic and therapeutic vaccines in an aggressive b16 lung metastatic melanoma model. immunization with mcmv-expressing ovalbumin (ova) induced a potent ov ...	2015	25633711
adap2 is an interferon stimulated gene that restricts rna virus entry.	interferon stimulated genes (isgs) target viruses at various stages of their infectious life cycles, including at the earliest stage of viral entry. here we identify arfgap with dual pleckstrin homology (ph) domains 2 (adap2) as a gene upregulated by type i ifn treatment in a stat1-dependent manner. adap2 functions as a gtpase-activating protein (gap) for arf6 and binds to phosphatidylinositol 3,4,5-trisphosphate (pi(3,4,5)p3) and pi(3,4)p2. we show that overexpression of adap2 suppresses dengue ...	2015	26372645
high-throughput single-cell kinetics of virus infections in the presence of defective interfering particles.	defective interfering particles (dips) are virus mutants that lack essential genes for growth. in coinfections with helper virus, the diversion of viral proteins to the replication and packaging of dip genomes can interfere with virus production. mounting cases of dips and dip-like genomes in clinical and natural isolates, as well as growing interest in dip-based therapies, underscore a need to better elucidate how dips work. dip activity is primarily measured by its inhibition of virus infectio ...	2015	26608322
duck interferon-inducible transmembrane protein 3 mediates restriction of influenza viruses.	interferon-inducible transmembrane proteins (ifitms) can restrict the entry of a wide range of viruses. ifitm3 localizes to endosomes and can potently restrict the replication of influenza a viruses (iav) and several other viruses that also enter host cells through the endocytic pathway. here, we investigate whether ifitms are involved in protection in ducks, the natural host of influenza virus. we identify and sequence duck ifitm1, ifitm2, ifitm3, and ifitm5. using quantitative pcr (qpcr), we d ...	2015	26468537
resistance to rhabdoviridae infection and subversion of antiviral responses.	interferon (ifn) treatment induces the expression of hundreds of ifn-stimulated genes (isgs). however, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. ifns inhibit rhabdovirus replication at different stages via the induction of a variety of isgs. this review will discuss how indivi ...	2015	26198243
immune protection against virus challenge in aging mice is not affected by latent herpesviral infections.	latent herpesvirus infections alter immune homeostasis. to understand if this results in aging-related loss of immune protection against emerging infections, we challenged old mice carrying latent mouse cytomegalovirus (cmv), herpes simplex virus 1 (hsv-1), and/or murine gammaherpesvirus 68 (mhv-68) with influenza virus, west nile virus (wnv), or vesicular stomatitis virus (vsv). we observed no increase in mortality or weight loss compared to results seen with herpesvirus-negative counterparts a ...	2015	26339051
rig-i is required for vsv-induced cytokine production by murine glia and acts in combination with dai to initiate responses to hsv-1.	a defining feature of viral central nervous system (cns) infection is the rapid onset of severe neuroinflammation. however, the mechanisms underlying glial responses to replicative neurotropic viruses are only now becoming apparent with the discovery of a number of cytosolic sensors for viral nucleic acids. we have described the expression by murine and human glial cells of two disparate pattern recognition receptors, retinoic acid inducible gene-i (rig-i) and dna-dependent activator of interfer ...	2015	26146945
antiviral, antifungal and antibacterial activities of a bodipy-based photosensitizer.	antimicrobial photodynamic inactivation (apdi) employing the bodipy-based photosensitizer 2,6-diiodo-1,3,5,7-tetramethyl-8-(n-methyl-4-pyridyl)-4,4'-difluoro-boradiazaindacene (dimpy-bodipy) was explored in an in vitro assay against six species of bacteria (eight total strains), three species of yeast, and three viruses as a complementary approach to their current drug-based or non-existent treatments. our best results achieved a noteworthy 5-6 log unit reduction in cfu at 0.1 μm for staphylococ ...	2015	26060922
a novel class of small molecule compounds that inhibit hepatitis c virus infection by targeting the prohibitin-craf pathway.	identification of novel drug targets and affordable therapeutic agents remains a high priority in the fight against chronic hepatitis c virus (hcv) infection. here, we report that the cellular proteins prohibitin 1 (phb1) and 2 (phb2) are pan-genotypic hcv entry factors functioning at a post-binding step. while predominantly found in mitochondria, phbs localize to the plasma membrane of hepatocytes through their transmembrane domains and interact with both egfr and craf. targeting phb by rocagla ...	2015	26870784
cloning, expression and antiviral activity of mink alpha-interferons.	as a key link between innate and adaptive immune responses, the interferon (ifn) system is the first line of defense against viral infection. ifn, and in particular, ifn-α, has been used clinically as an effective therapeutic agent for viral infections. however, different subtypes of ifn-α demonstrate distinct antiviral activity. therefore, it is important to identify ifn-α subtypes with high antiviral activity for the development of genetically engineered antiviral drugs.	2015	25889984
structure of the low ph conformation of chandipura virus g reveals important features in the evolution of the vesiculovirus glycoprotein.	chandipura virus (chav), a member of the vesiculovirus genus, is an emerging human pathogen. as for other rhabdoviruses, chav entry into susceptible cells is mediated by its single envelope glycoprotein g which is both involved in receptor recognition and fusion of viral and cellular membranes. here, we have characterized the fusion properties of chav-g. as for vesicular stomatitis virus (vsv, the prototype of the genus) g, fusion is triggered at low ph below 6.5. we have also analyzed the bioch ...	2015	25803715
cell entry of bovine ephemeral fever virus requires activation of src-jnk-ap1 and pi3k-akt-nf-κb pathways as well as cox-2-mediated pge2 /ep receptor signalling to enhance clathrin-mediated virus endocytosis.	although we have previously demonstrated that cell entry of bovine ephemeral fever virus (befv) follows a clathrin-mediated and dynamin 2-dependent endocytosis pathway, the cellular mechanism mediating virus entry remains unknown. here, we report that befv triggers simultaneously src-jnk-ap1 and pi3k-akt-nf-κb signalling pathways in the stage of virus binding to induce clathrin and dynamin 2 expressions, while vesicular stomatitis virus only activates src-jnk signalling to enhance its entry. act ...	2015	25582828
antiviral and antitumor activities of the lectin extracted from aspidistra elatior.	lectins, a group of highly diverse proteins of non-immune origin and are ubiquitously distributed in plants, animals and fungi, have multiple significant biological functions, such as anti-fungal, anti-viral and, most notably, anti-tumor activities. a lectin was purified from the rhizomes of aspidistra elatior blume, named a. elatior lectin (ael). in vitro experiments showed that the minimum inhibitory concentrations of ael against the vesicular stomatitis virus, coxsackie virus b4, and respirat ...	2015	25854839
antigenic requirement for gag in a vaccine that protects against high-dose mucosal challenge with simian immunodeficiency virus.	we reported previously on a vaccine approach that conferred apparent sterilizing immunity to sivsme660. the vaccine regimen employed a prime-boost using vectors based on recombinant vesicular stomatitis virus (vsv) and an alphavirus replicon expressing either siv gag or siv env. in the current study, we tested the ability of vectors expressing only the sivsme660 env protein to protect macaques against the same high-dose mucosal challenge. animals developed neutralizing antibody levels comparable ...	2015	25591175
abortively infected astrocytes appear to represent the main source of interferon beta in the virus-infected brain.	interferon beta (ifn-β) is a key component of cellular innate immunity in mammals, and it constitutes the first line of defense during viral infection. studies with cultured cells previously showed that almost all nucleated cells are able to produce ifn-β to various extents, but information about the in vivo sources of ifn-β remains incomplete. by applying immunohistochemistry and employing conditional-reporter mice that express firefly luciferase under the control of the ifn-β promoter in eithe ...	2015	26656686
λ-carrageenan p32 is a potent inhibitor of rabies virus infection.	rabies, caused by rabies virus (rabv), is an acute, fatal encephalitic disease that affects many warm-blooded mammals. currently, post-exposure prophylaxis regimens are effective for most rabies cases, but once the clinical signs of the disease appear, current treatment options become ineffective. carrageenan has been reported as a potent inhibitor of many viruses. in this study, the λ-carrageenan (λ-cg) p32 was investigated for its potential role in inhibiting rabv infection. our results show t ...	2015	26465753
vesicular stomatitis virus enables gene transfer and transsynaptic tracing in a wide range of organisms.	current limitations in technology have prevented an extensive analysis of the connections among neurons, particularly within nonmammalian organisms. we developed a transsynaptic viral tracer originally for use in mice, and then tested its utility in a broader range of organisms. by engineering the vesicular stomatitis virus (vsv) to encode a fluorophore and either the rabies virus glycoprotein (rabv-g) or its own glycoprotein (vsv-g), we created viruses that can transsynaptically label neuronal ...	2015	25688551
characterization of the interaction between the matrix protein of vesicular stomatitis virus and the immunoproteasome subunit lmp2.	the matrix protein (m) of vesicular stomatitis virus (vsv) is involved in virus assembly, budding, gene regulation, and cellular pathogenesis. using a yeast two-hybrid system, the m globular domain was shown to interact with lmp2, a catalytic subunit of the immunoproteasome (which replaces the standard proteasome catalytic subunit psmb6). the interaction was validated by coimmunoprecipitation of m and lmp2 in vsv-infected cells. the sites of interaction were characterized. a single mutation of m ...	2015	26311888
characterization of the biological activities and physicochemical characteristics of recombinant bovine interferon-α₁₄.	a boifn-α gene that included signal sequence was amplified from bovine liver genomic dna. the gene was named boifn-α14 according to the position at which the encoded gene of the bovine ifn was located in the bovine genome. the sequence included a 23-amino acid signal peptide and 166-amino acid mature peptide. the structural characteristics and phylogenetic relationships of the boifn-α14 gene were analyzed. a recombinant mature boifn-α14 (rboifn-α14) was expressed in the yeast pichia pastoris. an ...	2015	25480392
cloning, expression, and antiviral activity of interferon β from the chinese microbat, myotis davidii.	bats are natural reservoir hosts for many viruses that produce no clinical symptoms in bats. therefore, bats may have evolved effective mechanisms to control viral replication. however, little information is available on bat immune responses to viral infection. type i interferon (ifn) plays a key role in controlling viral infections. in this study, we report the cloning, expression, and biological activity of interferon β (ifnβ) from the chinese microbat species, myotis davidii. we demonstrated ...	2015	26645237
phosphatase pp4 negatively regulates type i ifn production and antiviral innate immunity by dephosphorylating and deactivating tbk1.	the effective recognition of viral infection and subsequent type i ifn production is essential for the host antiviral innate immune responses. the phosphorylation and activation of kinase tank-binding kinase 1 (tbk1) plays crucial roles in the production of type i ifn mediated by tlr and retinoic acid-inducible gene i-like receptors. type i ifn expression must be tightly regulated to prevent the development of immunopathological disorders. however, how the activated tbk1 is negatively regulated ...	2015	26363053
single-dose live-attenuated vesicular stomatitis virus-based vaccine protects african green monkeys from nipah virus disease.	nipah virus is a zoonotic paramyxovirus that causes severe respiratory and/or encephalitic disease in humans, often resulting in death. it is transmitted from pteropus fruit bats, which serve as the natural reservoir of the virus, and outbreaks occur on an almost annual basis in bangladesh or india. outbreaks are small and sporadic, and several cases of human-to-human transmission have been documented as an important feature of the epidemiology of nipah virus disease. there are no approved count ...	2015	25865472
pseudotyped retroviruses for infecting axolotl.	the ability to introduce dna elements into host cells and analyze the effects has revolutionized modern biology. here we describe a protocol to generate moloney murine leukemia virus (mmlv)-based, replication-incompetent pseudotyped retrovirus capable of infecting axolotls and incorporating genetic information into their genome. when pseudotyped with vesicular stomatitis virus (vsv)-g glycoprotein, the retroviruses can infect a broad range of proliferative axolotl cell types. however, if the ret ...	2015	25740482
interferon-α production by plasmacytoid dendritic cells is dispensable for an effective anti-cytomegalovirus response in adaptor protein-3-deficient mice.	adaptor protein-3 (ap-3) is a heterotetrameric complex, which regulates vesicular trafficking. mutations of the β3a subunit cause the hermansky-pudlak syndrome type 2 (hps-2), a rare genetic disease characterized by albinism, platelet defects, and recurrent infections. likewise, pearl mice, which lack functional ap-3, show several hps-2 defects. the ap-3 absence results in defective toll-like receptor trafficking and signaling in dendritic cells (dc), but its effect on the efficiency of the in v ...	2015	25333950
oncolytic viruses: from bench to bedside with a focus on safety.	oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents. several viruses have undergone evaluation in clinical trials in the last decades, and the first agent is about to be approved to be used as a novel cancer therapy modality. in the current review, an overview is presented on recent (pre)clinical developments in the field of oncolytic viruses that have previously been or currently are being evaluated in clinical trials. special attention is given to possible safety i ...	2015	25996182
use of recombinant virus replicon particles for vaccination against mycobacterium ulcerans disease.	buruli ulcer, caused by infection with mycobacterium ulcerans, is a necrotizing disease of the skin and subcutaneous tissue, which is most prevalent in rural regions of west african countries. the majority of clinical presentations seen in patients are ulcers on limbs that can be treated by eight weeks of antibiotic therapy. nevertheless, scarring and permanent disabilities occur frequently and buruli ulcer still causes high morbidity. a vaccine against the disease is so far not available but wo ...	2015	26275222
atf3 is a key regulator of macrophage ifn responses.	cytokines and ifns downstream of innate immune pathways are critical for mounting an appropriate immune response to microbial infection. however, the expression of these inflammatory mediators is tightly regulated, as uncontrolled production can result in tissue damage and lead to chronic inflammatory conditions and autoimmune diseases. activating transcription factor 3 (atf3) is an important transcriptional modulator that limits the inflammatory response by controlling the expression of a numbe ...	2015	26416280
deficiency of the b cell-activating factor receptor results in limited cd169+ macrophage function during viral infection.	the b cell-activating factor (baff) is critical for b cell development and humoral immunity in mice and humans. while the role of baff in b cells has been widely described, its role in innate immunity remains unknown. using baff receptor (baffr)-deficient mice, we characterized baffr-related innate and adaptive immune functions following infection with vesicular stomatitis virus (vsv) and lymphocytic choriomeningitis virus (lcmv). we identified a critical role for baffr signaling in the generati ...	2015	25673724
early effector cd8 t cells display plasticity in populating the short-lived effector and memory-precursor pools following bacterial or viral infection.	naïve antigen-specific cd8 t cells expand in response to infection and can be phenotypically separated into distinct effector populations, which include memory precursor effector cells (mpecs) and short-lived effector cells (slecs). in the days before the peak of the t cell response, a third population called early effector cells (eecs) predominate the antigen-specific response. however, the contribution of the eec population to the cd8 t cell differentiation program during an antimicrobial immu ...	2015	26191658
the sheep tetherin paralog obst2b blocks envelope glycoprotein incorporation into nascent retroviral virions.	bone marrow stromal cell antigen 2 (bst2) is a cellular restriction factor with a broad antiviral activity. in sheep, the bst2 gene is duplicated into two paralogs termed obst2a and obst2b. obst2a impedes viral exit of the jaagsiekte sheep retroviruses (jsrv), most probably by retaining virions at the cell membrane, similar to the "tethering" mechanism exerted by human bst2. in this study, we provide evidence that unlike obst2a, obst2b is limited to the golgi apparatus and disrupts jsrv envelope ...	2015	25339764
a recombinant vesicular stomatitis virus-based lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct lassa viruses.	lassa virus (lasv) is endemic in several west african countries and is the etiological agent of lassa fever. despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. genetically, lasv demonstrates a high degree of diversity that correlates with geographic distribution. the genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of ...	2015	25884628
vesicular stomatitis virus-based vaccines against lassa and ebola viruses.	we demonstrated that previous vaccination with a vesicular stomatitis virus (vsv)-based lassa virus vaccine does not alter protective efficacy of subsequent vaccination with a vsv-based ebola virus vaccine. these findings demonstrate the utility of vsv-based vaccines against divergent viral pathogens, even when preexisting immunity to the vaccine vector is present.	2015	25625358
identification of an antiviral host transmembrane protein march8.	membrane-associated ring-ch 8 (march8) is one of 11 members of the recently discovered march family of ring-finger e3 ubiquitin ligases. march8 downregulates several host transmembrane proteins; however, its physiological roles remain unknown. here we identify march8 as a novel antiviral factor. the overexpression of march8 in virus producing cells did not affect levels of lentivirus production, but markedly reduced viral infectivity. march8 blocked the incorporation of hiv-1 envelope glycoprote ...	2015	27760915
fluvastatin delays propagation of viral infection in isolated rat fdb myofibers but does not affect exocytic membrane trafficking.	we have utilized the enveloped viral model to study the effect of fluvastatin on membrane trafficking in isolated rat myofibers. our immunofluorescence studies constantly showed that infections in myofibers, which were treated with fluvastatin prior and during the infection with either vesicular stomatitis virus (vsv) or influenza a virus, propagated more slowly than in control myofibers without drug treatment. experiments with a virus expressing dad1 tagged with green fluorescent protein (gfp-d ...	2015	26123964
socs3 drives proteasomal degradation of tbk1 and negatively regulates antiviral innate immunity.	tank-binding kinase 1 (tbk1)-mediated induction of type i interferon (ifn) plays a critical role in host antiviral responses and immune homeostasis. the negative regulation of tbk1 activity is largely unknown. we report that suppressor of cytokine signaling 3 (socs3) inhibits the ifn-β signaling pathway by promoting proteasomal degradation of tbk1. overexpression and knockdown experiments indicated that socs3 is a negative regulator of ifn regulatory factor 3 (irf3) phosphorylation and ifn-β tra ...	2015	25939384
a cell-based screening system for anti-influenza a virus agents.	emerging of drug resistant influenza a virus (iav) has been a big challenge for anti-iav therapy. in this study, we describe a relatively easy and safe cell-based screening system for anti-iav replication inhibitors using a non-replicative strain of iav. a nickel (ii) complex of polyhydroxybenzaldehyde n4-thiosemicarbazone (nipt5) was recently found to exhibit anti-inflammatory activity in vivo and in vitro. nipt5 impedes the signaling cascades that lead to the activation of nf-κb in response to ...	2015	25728279
mxa interacts with and is modified by the sumoylation machinery.	mx proteins are evolutionarily conserved dynamin-like large gtpases involved in viral resistance triggered by types i and iii interferons. the human mxa is a cytoplasmic protein that confers resistance to a large number of viruses. the mxa protein is also known to self-assembly into high molecular weight homo-oligomers. using a yeast two-hybrid screen, we identified 27 mxa binding partners, some of which are related to the sumoylation machinery. the interaction of mxa with small-ubiquitin modifi ...	2015	25447205
experimental evolution of an rna virus in cells with innate immunity defects.	experimental evolution studies have shown that rna viruses respond rapidly to directional selection and thus can adapt efficiently to changes in host cell tropism, antiviral drugs, or other imposed selective pressures. however, the evolution of rna viruses under relaxed selection has been less extensively explored. here, we evolved vesicular stomatitis virus in mouse embryonic fibroblasts knocked-out for pkr, a protein with a central role in antiviral innate immunity. vesicular stomatitis virus ...	2015	27774280
vaccination with vesicular stomatitis virus-vectored chimeric hemagglutinins protects mice against divergent influenza virus challenge strains.	seasonal influenza virus infections continue to cause significant disease each year, and there is a constant threat of the emergence of reassortant influenza strains causing a new pandemic. available influenza vaccines are variably effective each season, are of limited scope at protecting against viruses that have undergone significant antigenic drift, and offer low protection against newly emergent pandemic strains. "universal" influenza vaccine strategies that focus on the development of humor ...	2015	26676789