Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
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| development of 2, 7-diamino-1, 8-naphthyridine (danp) anchored hairpin primers for rt-pcr detection of chikungunya virus infection. | a molecular diagnostic platform with danp-anchored hairpin primer was developed and evaluated for the rapid and cost-effective detection of chikungunya virus (chikv) with high sensitivity and specificity. the molecule 2, 7-diamino-1, 8-naphthyridine (danp) binds to a cytosine-bulge and emits fluorescence at 450 nm when it is excited by 400 nm light. thus, by measuring the decline in fluorescence emitted from danp-primer complexes after pcr reaction, we could monitor the pcr progress. by adapting ... | 2016 | 27571201 |
| detection of sindbis and inkoo virus rna in genetically typed mosquito larvae sampled in northern sweden. | mosquito-borne viruses have a widespread distribution across the globe and are known to pose serious threats to human and animal health. the maintenance and dissemination of these viruses in nature are driven through horizontal and vertical transmission. in the temperate climate of northern sweden, there is a dearth of knowledge on whether mosquito-borne viruses that occur are transmitted transovarially. to gain a better understanding of mosquito-borne virus circulation and maintenance, mosquito ... | 2016 | 27159120 |
| development and validation of a quantitative, one-step, multiplex, real-time reverse transcriptase pcr assay for detection of dengue and chikungunya viruses. | dengue virus (denv) and chikungunya virus (chikv) are important human pathogens with common transmission vectors and similar clinical presentations. patient care may be impacted by the misdiagnosis of denv and chikv in areas where both viruses cocirculate. in this study, we have developed and validated a one-step multiplex reverse transcriptase pcr (rt-pcr) to simultaneously detect, quantify, and differentiate between four denv serotypes (pan-denv) and chikungunya virus. the assay uses taqman te ... | 2016 | 27098955 |
| antagonism of the sodium-potassium atpase impairs chikungunya virus infection. | chikungunya virus (chikv) is a reemerging alphavirus that has caused epidemics of fever, arthralgia, and rash worldwide. there are currently no licensed vaccines or antiviral therapies available for the prevention or treatment of chikv disease. we conducted a high-throughput, chemical compound screen that identified digoxin, a cardiac glycoside that blocks the sodium-potassium atpase, as a potent inhibitor of chikv infection. treatment of human cells with digoxin or a related cardiac glycoside, ... | 2016 | 27222471 |
| identification of critical residues in hepatitis e virus macro domain involved in its interaction with viral methyltransferase and orf3 proteins. | hepatitis e virus (hev) is a major cause of hepatitis in normal and organ transplant individuals. hev open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (x-domain), v, duf3729 and y. the macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand rna viruses, playing important roles in multiple cellular processes. towards understanding the function of th ... | 2016 | 27113483 |
| vertical transmission of indian ocean lineage of chikungunya virus in aedes aegypti and aedes albopictus mosquitoes. | the re-emergence of chikungunya (chik) fever in thailand has been caused by a novel lineage of chikungunya virus (chikv) termed the indian ocean lineage (iol). the aedes albopictus mosquito is thought to be a primary vector of chik fever in thailand, whereas ae. aegypti acts as a secondary vector of the virus. the vertical transmission is believed to be a primary means to maintain chikv in nature and may be associated with an increased risk of outbreak. therefore, the goal of this study was to a ... | 2016 | 27108077 |
| dynamics of chikungunya virus cell entry unraveled by single-virus tracking in living cells. | chikungunya virus (chikv) is a rapidly emerging mosquito-borne human pathogen causing major outbreaks in africa, asia, and the americas. the cell entry pathway hijacked by chikv to infect a cell has been studied previously using inhibitory compounds. there has been some debate on the mechanism by which chikv enters the cell: several studies suggest that chikv enters via clathrin-mediated endocytosis, while others show that it enters independently of clathrin. here we applied live-cell microscopy ... | 2016 | 26912616 |
| assessment of productivity of culex spp. larvae (diptera: culicidae) in urban storm water catch basin system in wrocław (sw poland). | in urban environments, catch basins serve as major developmental and resting sites for anthropophilic and zoophilic mosquitoes. however, the use of this habitat is inconsistent, with abundance of larvae varying significantly across catch basins at a fine spatial scale. during seasonal summer investigations on mosquito species composition, their spatial and temporal distribution and the environmental characteristic of the breeding sites in the underground storm drain systems of the wrocław urban ... | 2016 | 26809340 |
| rainbow trout (oncorhynchus mykiss) muscle satellite cells are targets of salmonid alphavirus infection. | sleeping disease in rainbow trout is characterized by an abnormal swimming behaviour of the fish which stay on their side at the bottom of the tanks. this sign is due to extensive necrosis and atrophy of red skeletal muscle induced by the sleeping disease virus (sdv), also called salmonid alphavirus 2. infections of humans with arthritogenic alphaviruses, such as chikungunya virus (chikv), are global causes of debilitating musculoskeletal diseases. the mechanisms by which the virus causes these ... | 2016 | 26743565 |
| t cell-derived interleukin-10 is an important regulator of the th17 response during lethal alphavirus encephalomyelitis. | neuroadapted sindbis virus infection of mice causes t cell-mediated fatal encephalomyelitis. in the absence of il-10, pathogenic th17 cells are increased and disease is accelerated. lymphoid and myeloid cell contributions to il-10 production were determined using vertx il-10 transcriptional egfp reporter mice. effector and regulatory cd4(+) and cd8(+) t cells in the brain, but not the cervical lymph nodes, were the primary producers of il-10. th17 and th1/th17 cells were increased in mice that l ... | 2016 | 27235350 |
| alphavirus encephalomyelitis: mechanisms and approaches to prevention of neuronal damage. | mosquito-borne viruses are important causes of death and long-term neurologic disability due to encephalomyelitis. studies of mice infected with the alphavirus sindbis virus have shown that outcome is dependent on the age and genetic background of the mouse and virulence of the infecting virus. age-dependent susceptibility reflects the acquisition by neurons of resistance to virus replication and virus-induced cell death with maturation. in mature mice, the populations of neurons most susceptibl ... | 2016 | 27114366 |
| sindbis virus as a human pathogen-epidemiology, clinical picture and pathogenesis. | sindbis virus (sinv; family togaviridae, genus alphavirus) is an enveloped rna virus widely distributed in eurasia, africa, oceania and australia. sinv is transmitted among its natural bird hosts via mosquitoes. human disease caused by sinv infection has been reported mainly in south africa and in northern europe. vector mosquito abundance affects the annual incidence of sinv infections with occasional outbreaks of up to 1500 patients. symptoms include fever, malaise, rash and musculoskeletal pa ... | 2016 | 26990827 |
| concentration of sindbis virus with optimized gradient insulator-based dielectrophoresis. | biotechnology, separation science, and clinical research are impacted by microfluidic devices. separation and manipulation of bioparticles such as dna, protein and viruses are performed on these platforms. microfluidic systems provide many attractive features, including small sample size, rapid detection, high sensitivity and short processing time. dielectrophoresis (dep) and electrophoresis are especially well suited to microscale bioparticle control and have been demonstrated in many formats. ... | 2016 | 26878279 |
| synthesis and antiviral properties of novel indole-based thiosemicarbazides and 4-thiazolidinones. | a novel series of indolylthiosemicarbazides (6a-6g) and their cyclization products, 4-thiazolidinones (7a-7g), have been designed, synthesized and evaluated, in vitro, for their antiviral activity against a wide range of dna and rna viruses. compounds 6a, 6b, 6c and 6d exhibited notable antiviral activity against coxsackie b4 virus, at ec50 values ranging from 0.4 to 2.1 μg/ml. the selectivity index (ratio of cytotoxic to antivirally effective concentration) values of these compounds were betwee ... | 2016 | 26707844 |
| oncolytic viral therapy for neuroblastoma cells with sindbis virus ar339 strain. | with current treatment regimens, high-risk neuroblastoma (nb) remains largely incurable. oncolytic viral therapy uses replication-competent viruses, like sindbis virus (sinv), to kill cancers. the sinv ar339 strain is blood borne and relatively non-virulent. we evaluated the feasibility of sinv ar339 for treating human nb. | 2015 | 26298056 |
| differential action of pateamine a on translation of genomic and subgenomic mrnas from sindbis virus. | pateamine a (pat a) is a natural marine product that interacts specifically with the translation initiation factor eif4a leading to the disruption of the eif4f complex. in the present study, we have examined the activity of pat a on the translation of sindbis virus (sinv) mrnas. translation of genomic mrna is strongly suppressed by pat a, as shown by the reduction of nsp1 or nsp2 synthesis. notably, protein synthesis directed by subgenomic mrna is resistant to pat a inhibition when the compound ... | 2015 | 26057151 |
| trapping biases of culex torrentium and culex pipiens revealed by comparison of captures in cdc traps, ovitraps, and gravid traps. | we evaluate three trapping methods for their effectiveness at capturing culex pipiens and culex torrentium, both enzootic vectors of bird-associated viruses in europe. the comparisons, performed in two regions in sweden, were among cdc traps baited with carbon dioxide, gravid traps, and ovitraps baited with hay infusion. the proportions of the two culex species in a catch differed between trap types, with cdc traps catching a lower proportion of cx. torrentium than both gravid traps and ovitraps ... | 2015 | 26047196 |
| alteration of cell cycle progression by sindbis virus infection. | we examined the impact of sindbis virus (sinv) infection on cell cycle progression in a cancer cell line, hela, and a non-cancerous cell line, vero. cell cycle analyses showed that sinv infection is able to alter the cell cycle progression in both hela and vero cells, but differently, especially during the early stage of infection. sinv infection affected the expression of several cell cycle regulators (cdk4, cdk6, cyclin e, p21, cyclin a and cyclin b) in hela cells and caused hela cells to accu ... | 2015 | 25976675 |
| enhanced expression of trim14 gene suppressed sindbis virus reproduction and modulated the transcription of a large number of genes of innate immunity. | in the present research, we have studied an influence of enhanced expression trim14 on alphavirus sindbis (sinv, togaviridae family) infection. in the hek293 cells transfected with human trim14 gene (hek-trim14), sinv yield after infection was decreased 1000-10,000 times (3-4 lg of tcd50/ml) at 24 h p.i. and considerably less (1-2 lg of tcd50/ml) at 48 h p.i. analysis of the expression of 43 genes directly or indirectly involved in innate immune machine in hek-trim14 non-infected cells comparing ... | 2015 | 25948474 |
| 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 |
| different cortical projections from three subdivisions of the rat lateral posterior thalamic nucleus: a single-neuron tracing study with viral vectors. | the lateral posterior thalamic nucleus (lp) is one of the components of the extrageniculate pathway in the rat visual system, and is cytoarchitecturally divided into three subdivisions--lateral (lpl), rostromedial (lprm), and caudomedial (lpcm) portions. to clarify the differences in the dendritic fields and axonal arborisations among the three subdivisions, we applied a single-neuron labeling technique with viral vectors to lp neurons. the proximal dendrites of lpl neurons were more numerous th ... | 2015 | 25832313 |
| detection and isolation of sindbis virus from mosquitoes captured during an outbreak in sweden, 2013. | mosquito-borne alphaviruses have the potential to cause large outbreaks throughout the world. here we investigated the causative agent of an unexpected sindbis virus (sinv) outbreak during august-september, 2013, in a previously nonendemic region of sweden. mosquitoes were collected using carbon dioxide-baited cdc traps at locations close to human cases. the mosquitoes were initially screened as large pools by sinv-specific quantitative rt-pcr, and the sinv-positive mosquitoes were species deter ... | 2015 | 25700044 |
| a substitution in nsp1 combined with a double substitution in e2 glycoprotein renders sindbis-like virus xj-160 fully neurovirulent for adult mice. | sindbis virus (sv) can be rendered neurovirulent for adult mice by a double substitution within the e2 glycoprotein, including replacing gln at position 55 of e2 with a his (e2-55: gln-his) and e2-70: glu to lys. however, the mutant sindbis-like virus xj-160 with the double substitution (br-e5570) does not show neurovirulence for adult mice, although the mutant apparently reduced the average survival time of neonatal mice. to produce an xj-160 virus neurovirulent for adult mice, the br-e5570 vir ... | 2015 | 25449361 |
| inhibition of host protein synthesis by sindbis virus: correlation with viral rna replication and release of nuclear proteins to the cytoplasm. | infection of mammalian cells by sindbis virus (sinv) profoundly blocks cellular mrna translation. experimental evidence points to viral non-structural proteins (nsps), in particular nsp2, as the mediator of this inhibition. however, individual expression of nsp1, nsp2, nsp3 or nsp1-4 does not block cellular protein synthesis in bhk cells. trans-complementation of a defective sinv replicon lacking most of the coding region for nsps by the co-expression of nsp1-4 propitiates viral rna replication ... | 2015 | 25329362 |
| model-driven engineering of gene expression from rna replicons. | rna replicons are an emerging platform for engineering synthetic biological systems. replicons self-amplify, can provide persistent high-level expression of proteins even from a small initial dose, and, unlike dna vectors, pose minimal risk of chromosomal integration. however, no quantitative model sufficient for engineering levels of protein expression from such replicon systems currently exists. here, we aim to enable the engineering of multigene expression from more than one species of replic ... | 2015 | 24877739 |
| cryo-em structures elucidate neutralizing mechanisms of anti-chikungunya human monoclonal antibodies with therapeutic activity. | chikungunya virus (chikv) is a mosquito-transmitted alphavirus that causes severe acute and chronic disease in humans. although highly inhibitory murine and human monoclonal antibodies (mabs) have been generated, the structural basis of their neutralizing activity remains poorly characterized. here, we determined the cryo-em structures of chikungunya virus-like particles complexed with antibody fragments (fab) of two highly protective human mabs, 4j21 and 5m16, that block virus fusion with host ... | 2015 | 26504196 |
| myeloid cell arg1 inhibits control of arthritogenic alphavirus infection by suppressing antiviral t cells. | arthritogenic alphaviruses, including ross river virus (rrv) and chikungunya virus (chikv), are responsible for explosive epidemics involving millions of cases. these mosquito-transmitted viruses cause inflammation and injury in skeletal muscle and joint tissues that results in debilitating pain. we previously showed that arginase 1 (arg1) was highly expressed in myeloid cells in the infected and inflamed musculoskeletal tissues of rrv- and chikv-infected mice, and specific deletion of arg1 from ... | 2015 | 26436766 |
| la crosse virus field detection and vector competence of culex mosquitoes. | la crosse virus (lacv), a leading cause of arboviral pediatric encephalitis in the united states, is emerging in appalachia. here, we report field and laboratory evidence that suggest lacv may be using culex mosquitoes as additional vectors in this region. this bunyavirus was detected by reverse-transcriptase polymerase chain reaction in two pools of culex mosquitoes in southwestern virginia and in six pools in west virginia. to assess vector competence, we offered lacv blood meals to field-coll ... | 2015 | 26175029 |
| viral polymerase-helicase complexes regulate replication fidelity to overcome intracellular nucleotide depletion. | to date, the majority of work on rna virus replication fidelity has focused on the viral rna polymerase, while the potential role of other viral replicase proteins in this process is poorly understood. previous studies used resistance to broad-spectrum rna mutagens, such as ribavirin, to identify polymerases with increased fidelity that avoid misincorporation of such base analogues. we identified a novel variant in the alphavirus viral helicase/protease, nonstructural protein 2 (nsp2) that opera ... | 2015 | 26311883 |
| a potent neutralizing igm mab targeting the n218 epitope on e2 protein protects against chikungunya virus pathogenesis. | chikungunya virus (chikv) is a medically important human viral pathogen that causes chikungunya fever accompanied with debilitating and persistent joint pain. host-elicited or passively-transferred monoclonal antibodies (mab) are essential mediators of chikv clearance. therefore, this study aimed to generate and characterize a panel of mabs for their neutralization efficacy against chikv infection in a cell-based and murine model. to evaluate their antigenicity and neutralization profile, indire ... | 2015 | 26305993 |
| serial femtosecond x-ray diffraction of enveloped virus microcrystals. | serial femtosecond crystallography (sfx) using x-ray free-electron lasers has produced high-resolution, room temperature, time-resolved protein structures. we report preliminary sfx of sindbis virus, an enveloped icosahedral rna virus with ∼700 å diameter. microcrystals delivered in viscous agarose medium diffracted to ∼40 å resolution. small-angle diffuse x-ray scattering overlaid bragg peaks and analysis suggests this results from molecular transforms of individual particles. viral proteins un ... | 2015 | 26798819 |
| sec14l2 enables pan-genotype hcv replication in cell culture. | since its discovery in 1989, efforts to grow clinical isolates of the hepatitis c virus (hcv) in cell culture have met with limited success. only the jfh-1 isolate has the capacity to replicate efficiently in cultured hepatoma cells without cell culture-adaptive mutations. we hypothesized that cultured cells lack one or more factors required for the replication of clinical isolates. to identify the missing factors, we transduced huh-7.5 human hepatoma cells with a pooled lentivirus-based human c ... | 2015 | 26266980 |
| early events in chikungunya virus infection-from virus cell binding to membrane fusion. | chikungunya virus (chikv) is a rapidly emerging mosquito-borne alphavirus causing millions of infections in the tropical and subtropical regions of the world. chikv infection often leads to an acute self-limited febrile illness with debilitating myalgia and arthralgia. a potential long-term complication of chikv infection is severe joint pain, which can last for months to years. there are no vaccines or specific therapeutics available to prevent or treat infection. this review describes the crit ... | 2015 | 26198242 |
| the chikungunya virus capsid protein contains linear b cell epitopes in the n- and c-terminal regions that are dependent on an intact c-terminus for antibody recognition. | chikungunya virus (chikv) is an arthropod-borne agent that causes severe arthritic disease in humans and is considered a serious health threat in areas where competent mosquito vectors are prevalent. chikv has recently been responsible for several millions of cases of disease, involving over 40 countries. the recent re-emergence of chikv and its potential threat to human health has stimulated interest in better understanding of the biology and pathogenesis of the virus, and requirement for impro ... | 2015 | 26061335 |
| ability of the encephalitic arbovirus semliki forest virus to cross the blood-brain barrier is determined by the charge of the e2 glycoprotein. | semliki forest virus (sfv) provides a well-characterized model system to study the pathogenesis of virus encephalitis. several studies have used virus derived from the molecular clone sfv4. sfv4 virus does not have the same phenotype as the closely related l10 or the prototype virus from which its molecular clone was derived. in mice, l10 generates a high-titer plasma viremia, is efficiently neuroinvasive, and produces a fatal panencephalitis, whereas low-dose sfv4 produces a low-titer viremia, ... | 2015 | 25972559 |
| alphaviruses in gene therapy. | alphavirus vectors present an attractive approach for gene therapy applications due to the rapid and simple recombinant virus particle production and their broad range of mammalian host cell transduction. mainly three types of alphavirus vectors, namely naked rna, recombinant particles and dna/rna layered vectors, have been subjected to preclinical studies with the goal of achieving prophylactic or therapeutic efficacy, particularly in oncology. in this context, immunization with alphavirus vect ... | 2015 | 25961488 |
| native wolbachia from aedes albopictus blocks chikungunya virus infection in cellulo. | wolbachia, a widespread endosymbiont of terrestrial arthropods, can protect its host against viral and parasitic infections, a phenotype called "pathogen blocking". however, in some cases wolbachia may have no effect or even enhance pathogen infection, depending on the host-wolbachia-pathogen combination. the tiger mosquito aedes albopictus is naturally infected by two strains of wolbachia, walba and walbb, and is a competent vector for different arboviruses such as dengue virus (denv) and chiku ... | 2015 | 25923352 |
| noncapped alphavirus genomic rnas and their role during infection. | alphaviruses are enveloped positive-sense rna viruses that exhibit a wide host range consisting of vertebrate and invertebrate species. previously we have reported that the infectivity of sindbis virus (sinv), the model alphavirus, was largely a function of the cell line producing the viral particles. mammalian-cell-derived sinv particles, on average, exhibit a higher particle-to-pfu ratio than mosquito cell-derived sinv particles. nevertheless, the outcome of nonproductive infection, the molecu ... | 2015 | 25833042 |
| nuclear proteins hijacked by mammalian cytoplasmic plus strand rna viruses. | plus strand rna viruses that replicate in the cytoplasm face challenges in supporting the numerous biosynthetic functions required for replication and propagation. most of these viruses are genetically simple and rely heavily on co-opting cellular proteins, particularly cellular rna-binding proteins, into new roles for support of virus infection at the level of virus-specific translation, and building rna replication complexes. in the course of infectious cycles many nuclear-cytoplasmic shuttlin ... | 2015 | 25818028 |
| fighting arbovirus transmission: natural and engineered control of vector competence in aedes mosquitoes. | control of aedine mosquito vectors, either by mosquito population reduction or replacement with refractory mosquitoes, may play an essential role in the fight against arboviral diseases. in this review, we will focus on the development and application of biological approaches, both natural or engineered, to limit mosquito vector competence for arboviruses. the study of mosquito antiviral immunity has led to the identification of a number of host response mechanisms and proteins that are required ... | 2015 | 26463078 |
| viral rna intermediates as targets for detection and discovery of novel and emerging mosquito-borne viruses. | mosquito-borne viruses encompass a range of virus families, comprising a number of significant human pathogens (e.g., dengue viruses, west nile virus, chikungunya virus). virulent strains of these viruses are continually evolving and expanding their geographic range, thus rapid and sensitive screening assays are required to detect emerging viruses and monitor their prevalence and spread in mosquito populations. double-stranded rna (dsrna) is produced during the replication of many of these virus ... | 2015 | 25799391 |
| dissecting the role of e2 protein domains in alphavirus pathogenicity. | alphaviruses represent a diverse set of arboviruses, many of which are important pathogens. chikungunya virus (chikv), an arthritis-inducing alphavirus, is the cause of a massive ongoing outbreak in the caribbean and south america. in contrast to chikv, other related alphaviruses, such as venezuelan equine encephalitis virus (veev) and semliki forest virus (sfv), can cause encephalitic disease. e2, the receptor binding protein, has been implicated as a determinant in cell tropism, host range, pa ... | 2015 | 26676771 |
| loss of glycosaminoglycan receptor binding after mosquito cell passage reduces chikungunya virus infectivity. | chikungunya virus (chikv) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. chikv that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. herein, we compare replication, pathogenicity, and receptor binding of chikv generated in vero cells (mammal) or c6/36 cells (mosquito) through a single passage. we demonstrate that mosquito cell-derived chikv (chikv mos) has s ... | 2015 | 26484530 |
| eastern equine encephalitis virus in mice ii: pathogenesis is dependent on route of exposure. | eastern equine encephalitis virus (eeev) is an alphavirus with a case fatality rate estimated to be as high as 75 % in humans and 90 % in horses. surviving patients often have long-lasting and severe neurological sequelae. at present, there is no licensed vaccine or therapeutic for eeev infection. this study completes the clinical and pathological analysis of mice infected with a north american strain of eeev by three different routes: aerosol, intranasal, and subcutaneous. such an understanding ... | 2015 | 26423229 |
| the virus-host interplay: biogenesis of +rna replication complexes. | positive-strand rna (+rna) viruses are an important group of human and animal pathogens that have significant global health and economic impacts. notable members include west nile virus, dengue virus, chikungunya, severe acute respiratory syndrome (sars) coronavirus and enteroviruses of the picornaviridae family.unfortunately, prophylactic and therapeutic treatments against these pathogens are limited. +rna viruses have limited coding capacity and thus rely extensively on host factors for succes ... | 2015 | 26287230 |
| production of a sindbis/eastern equine encephalitis chimeric virus inactivated cell culture antigen. | eastern equine encephalitis virus (eeev) is a medically important pathogen that can cause severe encephalitis in humans, with mortality rates ranging from 30 to 80%. unfortunately there are no antivirals or licensed vaccines available for human use, and laboratory diagnosis is essential to differentiate eeev infection from other pathogens with similar clinical manifestations. the arboviral diseases branch (adb) reference laboratory at the cdc division of vector-borne diseases (dvbd) produces ref ... | 2015 | 26205552 |
| tissue barriers to arbovirus infection in mosquitoes. | arthropod-borne viruses (arboviruses) circulate in nature between arthropod vectors and vertebrate hosts. arboviruses often cause devastating diseases in vertebrate hosts, but they typically do not cause significant pathology in their arthropod vectors. following oral acquisition of a viremic bloodmeal from a vertebrate host, the arbovirus disease cycle requires replication in the cellular environment of the arthropod vector. once the vector has become systemically and persistently infected, the ... | 2015 | 26184281 |
| an alphavirus temperature-sensitive capsid mutant reveals stages of nucleocapsid assembly. | alphaviruses have a nucleocapsid core composed of the rna genome surrounded by an icosahedral lattice of capsid protein. an insertion after position 186 in the capsid protein produced a strongly temperature-sensitive growth phenotype. even when the structural proteins were synthesized at the permissive temperature (28°c), subsequent incubation of the cells at the non-permissive temperature (37°c) dramatically decreased mutant capsid protein stability and particle assembly. electron microscopy co ... | 2015 | 26051211 |
| do we need a vaccine against chikungunya? | during the last decade, the chikungunya (chikv) virus has expanded its range of activity, conquering new territories and becoming an important global health threat. in particular, the challenge represented by the recent emergence of chikv in the americas has strengthened the need of a safe and effective vaccine. although research on vaccines against chikv has been slow, a few vaccine candidates have been tested over the years. inactivated and attenuated vaccine candidates have shown promising re ... | 2015 | 25971340 |
| sindbis virus interferes with dengue 4 virus replication and its potential transmission by aedes albopictus. | mosquitoes transmit a number of arboviruses associated with disease outbreaks in humans and other animals. the majority of medically important arboviruses belong to three families: togaviridae, flaviviridae and bunyaviridae. several members of these families have overlapping distributions and share common vectors, increasing the potential for arboviral coinfections. this study examined how two model viruses: sindbis virus (sinv, togaviridae: alphavirus) and dengue-4 virus (denv-4, flaviviridae: ... | 2015 | 25633862 |
| syndromic approach to arboviral diagnostics for global travelers as a basis for infectious disease surveillance. | arboviruses have overlapping geographical distributions and can cause symptoms that coincide with more common infections. therefore, arbovirus infections are often neglected by travel diagnostics. here, we assessed the potential of syndrome-based approaches for diagnosis and surveillance of neglected arboviral diseases in returning travelers. | 2015 | 26372010 |
| global emergence of alphaviruses that cause arthritis in humans. | arthropod-borne viruses (arboviruses) may cause severe emerging and re-emerging infectious diseases, which pose a significant threat to human and animal health in the world today. these infectious diseases range from mild febrile illnesses, arthritis, and encephalitis to haemorrhagic fevers. it is postulated that certain environmental factors, vector competence, and host susceptibility have a major impact on the ecology of arboviral diseases. presently, there is a great interest in the emergence ... | 2015 | 26689654 |
| genetic dissection of the host tropism of human-tropic pathogens. | infectious diseases are the second leading cause of death worldwide. although the host multitropism of some pathogens has rendered their manipulation possible in animal models, the human-restricted tropism of numerous viruses, bacteria, fungi, and parasites has seriously hampered our understanding of these pathogens. hence, uncovering the genetic basis underlying the narrow tropism of such pathogens is critical for understanding their mechanisms of infection and pathogenesis. moreover, such gene ... | 2015 | 26407032 |
| a fast cross-validation method for alignment of electron tomography images based on beer-lambert law. | in electron tomography, accurate alignment of tilt series is an essential step in attaining high-resolution 3d reconstructions. nevertheless, quantitative assessment of alignment quality has remained a challenging issue, even though many alignment methods have been reported. here, we report a fast and accurate method, tomoaligneval, based on the beer-lambert law, for the evaluation of alignment quality. our method is able to globally estimate the alignment accuracy by measuring the goodness of l ... | 2015 | 26455556 |
| mammalian synthetic biology: emerging medical applications. | in this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. we start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. a comprehensive list of on-off switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. subsequently, boolean logic gates, synthetic mammalian oscillators and toggle ... | 2015 | 25808341 |
| chikungunya virus (chikv) inhibitors from natural sources: a medicinal chemistry perspective. | chikungunya virus (chikv) is one of the re-emerging "neglected" tropical diseases whose recent outbreak affected not only africa and south-east asia but also several parts of america and europe. to date, despite its serious nature, no antivirals or vaccines were developed in order to counter this resurgent infectious disease. the recent advancement in crystallography and availability of crystal structures of certain domains of chikv initiates the development of anti-chikv agents using structure- ... | 2015 | 25921858 |
| sequence analysis reveals a conserved extension in the capping enzyme of the alphavirus supergroup, and a homologous domain in nodaviruses. | members of the alphavirus supergroup include human pathogens such as chikungunya virus, hepatitis e virus and rubella virus. they encode a capping enzyme with methyltransferase-guanylyltransferase (mtase-gtase) activity, which is an attractive drug target owing to its unique mechanism. however, its experimental study has proven very difficult. | 2015 | 25886938 |
| bovine lactoferrin inhibits toscana virus infection by binding to heparan sulphate. | toscana virus is an emerging sandfly-borne bunyavirus in mediterranean europe responsible for neurological diseases in humans. it accounts for about 80% of paediatric meningitis cases during the summer. despite the important impact of toscana virus infection-associated disease on human health, currently approved vaccines or effective antiviral treatments are not available. in this research, we have analyzed the effect of bovine lactoferrin, a bi-globular iron-binding glycoprotein with potent ant ... | 2015 | 25643293 |
| rna degradation in antiviral immunity and autoimmunity. | post-transcriptional control determines the fate of cellular rna molecules. nonsense-mediated decay (nmd) provides quality control of mrna, targeting faulty cellular transcripts for degradation by multiple nucleases including the rna exosome. recent findings have revealed a role for nmd in targeting viral rna molecules, thereby restricting virus infection. interestingly, nmd is also linked to immune responses at another level: mutations affecting the nmd or rna exosome machineries cause chronic ... | 2015 | 25709093 |
| emerging roles for rna degradation in viral replication and antiviral defense. | viral replication significantly alters the gene expression landscape of infected cells. many of these changes are driven by viral manipulation of host transcription or translation machinery. several mammalian viruses encode factors that broadly dampen gene expression by directly targeting messenger rna (mrna). here, we highlight how these factors promote mrna degradation to globally regulate both host and viral gene expression. although these viral factors are not homologous and use distinct mec ... | 2015 | 25721579 |
| the role of rna interference (rnai) in arbovirus-vector interactions. | rna interference (rnai) was shown over 18 years ago to be a mechanism by which arbovirus replication and transmission could be controlled in arthropod vectors. during the intervening period, research on rnai has defined many of the components and mechanisms of this antiviral pathway in arthropods, yet a number of unexplored questions remain. rnai refers to rna-mediated regulation of gene expression. originally, the term described silencing of endogenous genes by introduction of exogenous double- ... | 2015 | 25690800 |
| viral and cellular proteins containing fgdf motifs bind g3bp to block stress granule formation. | the ras-gap sh3 domain-binding proteins (g3bp) are essential regulators of the formation of stress granules (sg), cytosolic aggregates of proteins and rna that are induced upon cellular stress, such as virus infection. many viruses, including semliki forest virus (sfv), block sg induction by targeting g3bp. in this work, we demonstrate that the g3bp-binding motif of sfv nsp3 consists of two fgdf motifs, in which both phenylalanine and the glycine residue are essential for binding. in addition, w ... | 2015 | 25658430 |
| stress granule components g3bp1 and g3bp2 play a proviral role early in chikungunya virus replication. | stress granules (sgs) are protein-mrna aggregates that are formed in response to environmental stresses, resulting in translational inhibition. sgs are generally believed to play an antiviral role and are manipulated by many viruses, including various alphaviruses. gtpase-activating protein (sh3 domain)-binding protein 1 (g3bp1) is a key component and commonly used marker of sgs. its homolog g3bp2 is a less extensively studied sg component. here, we demonstrate that chikungunya virus (chikv) inf ... | 2015 | 25653451 |
| atp1a1-mediated src signaling inhibits coronavirus entry into host cells. | in addition to transporting ions, the multisubunit na(+),k(+)-atpase also functions by relaying cardiotonic steroid (cts)-binding-induced signals into cells. in this study, we analyzed the role of na(+),k(+)-atpase and, in particular, of its atp1a1 α subunit during coronavirus (cov) infection. as controls, the vesicular stomatitis virus (vsv) and influenza a virus (iav) were included. using gene silencing, the atp1a1 protein was shown to be critical for infection of cells with murine hepatitis v ... | 2015 | 25653449 |
| arbovirus-mosquito interactions: rnai pathway. | arthropod-borne (arbo) viruses infect hematophagous arthropods (vectors) to maintain virus transmission between vertebrate hosts. the mosquito vector actively controls arbovirus infection to minimize its fitness costs. the rna interference (rnai) pathway is the major antiviral response vectors use to restrict arbovirus infections. we know this because depleting rnai gene products profoundly impacts arbovirus replication, the antiviral rnai pathway genes undergo positive, diversifying selection a ... | 2015 | 26629932 |
| fluorescent protein-tagged sindbis virus e2 glycoprotein allows single particle analysis of virus budding from live cells. | sindbis virus (sinv) is an enveloped, mosquito-borne alphavirus. here we generated and characterized a fluorescent protein-tagged (fp-tagged) sinv and found that the presence of the fp-tag (mcherry) affected glycoprotein transport to the plasma membrane whereas the specific infectivity of the virus was not affected. we examined the virions by transmission electron cryo-microscopy and determined the arrangement of the fp-tag on the surface of the virion. the fluorescent proteins are arranged icos ... | 2015 | 26633461 |
| battle between influenza a virus and a newly identified antiviral activity of the parp-containing zapl protein. | previous studies showed that zapl (parp-13.1) exerts its antiviral activity via its n-terminal zinc fingers that bind the mrnas of some viruses, leading to mrna degradation. here we identify a different antiviral activity of zapl that is directed against influenza a virus. this zapl antiviral activity involves its c-terminal parp domain, which binds the viral pb2 and pa polymerase proteins, leading to their proteasomal degradation. after the pb2 and pa proteins are poly(adp-ribosylated), they ar ... | 2015 | 26504237 |
| sphingosine kinase 2 is a chikungunya virus host factor co-localized with the viral replication complex. | chikungunya virus (chikv) is a re-emerging alphavirus which causes severe and prolonged arthralgic febrile illness. the recent global spread of the virus and lack of approved therapeutic options makes it imperative to gain greater insight into the molecular mechanisms underlying chikv pathogenesis, in particular host factors recruited by the virus. in the current study, we identify sphingosine kinase 2 (sk2) as a chikv host factor co-localized with the viral replication complex (vrc) during infe ... | 2015 | 26576339 |
| immunoproteomic profiling of antiviral antibodies in new-onset type 1 diabetes using protein arrays. | the rapid rise in the incidence of type 1 diabetes (t1d) suggests the involvement of environmental factors including viral infections. we evaluated the association between viral infections and t1d by profiling antiviral antibodies using a high-throughput immunoproteomics approach in patients with new-onset t1d. we constructed a viral protein array comprising the complete proteomes of seven viruses associated with t1d and open reading frames from other common viruses. antibody responses to 646 vi ... | 2015 | 26450993 |
| interactions involved in ph protection of the alphavirus fusion protein. | the alphavirus membrane protein e1 mediates low ph-triggered fusion of the viral and endosome membranes during virus entry. during virus biogenesis e1 associates as a heterodimer with the transmembrane protein p62. late in the secretory pathway, cellular furin cleaves p62 to the mature e2 protein and a peripheral protein e3. e3 remains bound to e2 at low ph, stabilizing the heterodimer and thus protecting e1 from the acidic ph of the secretory pathway. release of e3 at neutral ph then primes the ... | 2015 | 26433749 |
| mosquito rasputin interacts with chikungunya virus nsp3 and determines the infection rate in aedes albopictus. | chikungunya virus (chikv) is an arthritogenic alphavirus (family togaviridae), transmitted by aedes species mosquitoes. chikv re-emerged in 2004 with multiple outbreaks worldwide and recently reached the americas where it has infected over a million individuals in a rapidly expanding epidemic. while alphavirus replication is well understood in general, the specific function (s) of non-structural protein nsp3 remain elusive. chikv nsp3 modulates the mammalian stress response by preventing stress ... | 2015 | 26384002 |
| japanese encephalitis virus replicon-based vaccine expressing enterovirus-71 epitope confers dual protection from lethal challenges. | to construct safer recombinant flavivirus vaccine, we exploited japanese encephalitis virus (jev) replicon-based platform to generate single-round infectious particles (srips) that expressed heterologous neutralizing epitope sp70 derived from enterovirus-71 (ev71). such pseudo-infectious virus particles, named srip-sp70, although are not genuine viable viruses, closely mimic live virus infection to elicit immune responses within one round of viral life cycle. | 2015 | 26362772 |
| differential phosphatidylinositol-3-kinase-akt-mtor activation by semliki forest and chikungunya viruses is dependent on nsp3 and connected to replication complex internalization. | many viruses affect or exploit the phosphatidylinositol-3-kinase (pi3k)-akt-mammalian target of rapamycin (mtor) pathway, a crucial prosurvival signaling cascade. we report that this pathway was strongly activated in cells upon infection with the old world alphavirus semliki forest virus (sfv), even under conditions of complete nutrient starvation. we mapped this activation to the hyperphosphorylated/acidic domain in the c-terminal tail of sfv nonstructural protein nsp3. viruses with a deletion ... | 2015 | 26339054 |
| alphavirus rna synthesis and non-structural protein functions. | the members of the genus alphavirus are positive-sense rna viruses, which are predominantly transmitted to vertebrates by a mosquito vector. alphavirus disease in humans can be severely debilitating, and depending on the particular viral species, infection may result in encephalitis and possibly death. in recent years, alphaviruses have received significant attention from public health authorities as a consequence of the dramatic emergence of chikungunya virus in the indian ocean islands and the ... | 2015 | 26219641 |
| dna-launched alphavirus replicons encoding a fusion of mycobacterial antigens acr and ag85b are immunogenic and protective in a murine model of tb infection. | there is an urgent need for effective prophylactic measures against mycobacterium tuberculosis (mtb) infection, particularly given the highly variable efficacy of bacille calmette-guerin (bcg), the only licensed vaccine against tuberculosis (tb). most studies indicate that cell-mediated immune responses involving both cd4+ and cd8+ t cells are necessary for effective immunity against mtb. genetic vaccination induces humoral and cellular immune responses, including cd4+ and cd8+ t-cell responses, ... | 2015 | 26317509 |
| differences in processing determinants of nonstructural polyprotein and in the sequence of nonstructural protein 3 affect neurovirulence of semliki forest virus. | the a7(74) strain of semliki forest virus (sfv; genus alphavirus) is avirulent in adult mice, while the l10 strain is virulent in mice of all ages. it has been previously demonstrated that this phenotypic difference is associated with nonstructural protein 3 (nsp3). consensus clones of l10 (designated sfv6) and a7(74) (designated a774wt) were used to construct a panel of recombinant viruses. the insertion of nsp3 from a774wt into the sfv6 backbone had a minor effect on the virulence of the resul ... | 2015 | 26311875 |
| microrna-attenuated clone of virulent semliki forest virus overcomes antiviral type i interferon in resistant mouse ct-2a glioma. | glioblastoma is a terminal disease with no effective treatment currently available. among the new therapy candidates are oncolytic viruses capable of selectively replicating in cancer cells, causing tumor lysis and inducing adaptive immune responses against the tumor. however, tumor antiviral responses, primarily mediated by type i interferon (ifn-i), remain a key problem that severely restricts viral replication and oncolysis. we show here that the semliki forest virus (sfv) strain sfv4, which ... | 2015 | 26269187 |
| flavivirus rna synthesis in vitro. | establishment of in vitro systems to study mechanisms of rna synthesis for positive strand rna viruses have been very useful in the past and have shed light on the composition of protein and rna components, optimum conditions, the nature of the products formed, cis-acting rna elements and trans-acting protein factors required for efficient synthesis. in this review, we summarize our current understanding regarding the requirements for flavivirus rna synthesis in vitro. we describe details of rea ... | 2015 | 26272247 |
| haploid genetic screen reveals a profound and direct dependence on cholesterol for hantavirus membrane fusion. | hantaviruses cause hemorrhagic fever with renal syndrome (hfrs) in the old world and a highly fatal hantavirus cardiopulmonary syndrome (hcps) in the new world. no vaccines or antiviral therapies are currently available to prevent or treat hantavirus disease, and gaps in our understanding of how hantaviruses enter cells challenge the search for therapeutics. we performed a haploid genetic screen in human cells to identify host factors required for entry by andes virus, a highly virulent new worl ... | 2015 | 26126854 |
| a novel system for visualizing alphavirus assembly. | alphaviruses are small, enveloped rna viruses that form infectious particles by budding through the cellular plasma membrane. to help visualize and understand the intracellular assembly of alphavirus virions we have developed a bimolecular fluorescence complementation-based system (bifc) that allows visualization of capsid and e2 subcellular localization and association in live cells. in this system, n- or c-terminal venus fluorescent protein fragments (vn- and vc-) are fused to the n-terminus o ... | 2015 | 26122073 |
| distinct sets of piwi proteins produce arbovirus and transposon-derived pirnas in aedes aegypti mosquito cells. | the piwi-interacting rna (pirna) pathway is essential for transposon silencing in many model organisms. its remarkable efficiency relies on a sophisticated amplification mechanism known as the ping-pong loop. in alphavirus-infected aedes mosquitoes, pirnas with sequence features that suggest ping-pong-dependent biogenesis are produced from viral rna. the piwi family in aedes mosquitoes is expanded when compared to other model organisms, raising the possibility that individual piwi proteins have ... | 2015 | 26068474 |
| mrna capping by venezuelan equine encephalitis virus nsp1: functional characterization and implications for antiviral research. | alphaviruses are known to possess a unique viral mrna capping mechanism involving the viral nonstructural protein nsp1. this enzyme harbors methyltransferase (mtase) and nsp1 guanylylation (gt) activities catalyzing the transfer of the methyl group from s-adenosylmethionine (adomet) to the n7 position of a gtp molecule followed by the formation of an m(7)gmp-nsp1 adduct. subsequent transfer of m(7)gmp onto the 5' end of the viral mrna has not been demonstrated in vitro yet. here we report the bi ... | 2015 | 26041283 |
| conformational changes required for reovirus cell entry are sensitive to ph. | during cell entry, reovirus particles disassemble to generate isvps. isvps undergo conformational changes to form isvp(*) and this conversion is required for membrane penetration. in tissues where isvp formation occurs within endosomes, isvp-to-isvp(*) conversion occurs at low ph. in contrast, in tissues where isvp formation occurs extracellularly, isvp-to-isvp(*) transition occurs at neutral ph. whether these two distinct ph environments influence the efficiency of cell entry is not known. in t ... | 2015 | 26004253 |
| the broad-spectrum antiviral protein zap restricts human retrotransposition. | intrinsic immunity describes the set of recently discovered but poorly understood cellular mechanisms that specifically target viral pathogens. their discovery derives in large part from intensive studies of hiv and siv that revealed restriction factors acting at various stages of the retroviral life cycle. recent studies indicate that some factors restrict both retroviruses and retrotransposons but surprisingly in ways that may differ. we screened known interferon-stimulated antiviral proteins ... | 2015 | 26001115 |
| antiviral antibody profiling by high-density protein arrays. | viral infections elicit antiviral antibodies and have been associated with various chronic diseases. detection of these antibodies can facilitate diagnosis, treatment of infection, and understanding of the mechanisms of virus-associated diseases. in this work, we assayed antiviral antibodies using a novel high-density nucleic acid programmable protein array (hd-nappa) platform. individual viral proteins were expressed in situ directly from plasmids encoding proteins in an array of microscopic re ... | 2015 | 25758251 |
| shp-1-dependent macrophage differentiation exacerbates virus-induced myositis. | virus-induced myositis is an emerging global affliction that remains poorly characterized with few treatment options. moreover, muscle-tropic viruses often spread to the cns, causing dramatically increased morbidity. therefore, there is an urgent need to explore genetic factors involved in this class of human disease. this report investigates critical innate immune pathways affecting murine virus-induced myositis. of particular importance, the key immune regulator src homology region 2 domain-co ... | 2015 | 25681345 |
| the 5' and 3' ends of alphavirus rnas--non-coding is not non-functional. | the non-coding regions found at the 5' and 3' ends of alphavirus genomes regulate viral gene expression, replication, translation and virus-host interactions, which have significant implications for viral evolution, host range, and pathogenesis. the functions of these non-coding regions are mediated by a combination of linear sequence and structural elements. the capped 5' untranslated region (utr) contains promoter elements, translational regulatory sequences that modulate dependence on cellula ... | 2015 | 25630058 |
| recovery of recombinant crimean congo hemorrhagic fever virus reveals a function for non-structural glycoproteins cleavage by furin. | crimean congo hemorrhagic fever virus (cchfv) is a negative-strand rna virus of the family bunyaviridae (genus: nairovirus). in humans, cchfv causes fever, hemorrhage, severe thrombocytopenia, and high fatality. a major impediment in precisely determining the basis of cchfv's high pathogenicity has been the lack of methodology to produce recombinant cchfv. we developed a reverse genetics system based on transfecting plasmids into bsr-t7/5 and huh7 cells. in our system, bacteriophage t7 rna polym ... | 2015 | 25933376 |
| both rig-i and mda5 detect alphavirus replication in concentration-dependent mode. | alphaviruses are a family of positive-strand rna viruses that circulate on all continents between mosquito vectors and vertebrate hosts. despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus-host interaction are insufficiently understood. in this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. our new da ... | 2015 | 26550947 |
| region-specific dendritic simplification induced by aβ, mediated by tau via dysregulation of microtubule dynamics: a mechanistic distinct event from other neurodegenerative processes. | dendritic simplification, a key feature of the neurodegenerative triad of alzheimer's disease (ad) in addition to spine changes and neuron loss, occurs in a region-specific manner. however, it is unknown how changes in dendritic complexity are mediated and how they relate to spine changes and neuron loss. | 2015 | 26541821 |
| beclin 1-vps34 complex architecture: understanding the nuts and bolts of therapeutic targets. | autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. dysregulation of autophagy is linked to a growing number of human diseases. the beclin 1-vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. manipulation of autophagy, in particular via modulation of the action of the beclin 1-vps34 complexes, is considered a ... | 2015 | 26692106 |
| an odyssey in antiviral drug development-50 years at the rega institute: 1964-2014. | 2015 | 26713268 | |
| the hub protein loquacious connects the microrna and short interfering rna pathways in mosquitoes. | aedes aegypti mosquitoes vector several arboviruses of global health significance, including dengue viruses and chikungunya virus. rna interference (rnai) plays an important role in antiviral immunity, gene regulation and protection from transposable elements. double-stranded rna binding proteins (dsrbps) are important for efficient rnai; in drosophila functional specialization of the mirna, endo-sirna and exo-sirna pathway is aided by the dsrbps loquacious (loqs-pb, loqs-pd) and r2d2, respectiv ... | 2015 | 25765650 |
| simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo. | despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. accordingly, we developed a photometric patch electrode (pme) to overcome the depth limitation of optical measurements and also enable the simultaneous recor ... | 2015 | 25761950 |
| activation of tomato bushy stunt virus rna-dependent rna polymerase by cellular heat shock protein 70 is enhanced by phospholipids in vitro. | similar to other positive-strand rna viruses, tombusviruses are replicated by the membrane-bound viral replicase complex (vrc). the vrc consists of the p92 virus-coded rna-dependent rna polymerase (rdrp), the viral p33 rna chaperone, and several co-opted host proteins. in order to become a functional rdrp after its translation, the p92 replication protein should be incorporated into the vrc, followed by its activation. we have previously shown in a cell-free yeast extract-based assay that the ac ... | 2015 | 25762742 |
| role of zinc-finger anti-viral protein in host defense against sindbis virus. | accumulating evidence indicates that type i interferon (ifn) mediates the host protective response to rna viruses. however, the anti-viral effector molecules involved in this response have not been fully identified. here, we show that zinc-finger anti-viral protein (zap), an ifn-inducible gene, plays a critical role in the elimination of sindbis virus (sinv) in vitro and in vivo. the loss of zap greatly enhances the replication of sinv but does not inhibit type i ifn production in primary mouse ... | 2015 | 25758257 |
| mechanisms of innate immune evasion in re-emerging rna viruses. | recent outbreaks of ebola, west nile, chikungunya, middle eastern respiratory and other emerging/re-emerging rna viruses continue to highlight the need to further understand the virus-host interactions that govern disease severity and infection outcome. as part of the early host antiviral defense, the innate immune system mediates pathogen recognition and initiation of potent antiviral programs that serve to limit virus replication, limit virus spread and activate adaptive immune responses. conc ... | 2015 | 25765605 |
| the role of misshapen nck-related kinase (mink), a novel ste20 family kinase, in the ires-mediated protein translation of human enterovirus 71. | human enterovirus 71 (ev71) commonly causes hand, foot and mouth disease in young children, and occasional occurrences of neurological complications can be fatal. in this study, a high-throughput cell-based screening on the serine/threonine kinase sirna library was performed to identify potential antiviral agents against ev71 replication. among the hits, misshapen/niks-related kinase (mink) was selected for detailed analysis due to its strong inhibitory profile and novelty. in the investigation ... | 2015 | 25747578 |
| xrn1 stalling in the 5' utr of hepatitis c virus and bovine viral diarrhea virus is associated with dysregulated host mrna stability. | we demonstrate that both hepatitis c virus (hcv) and bovine viral diarrhea virus (bvdv) contain regions in their 5' utrs that stall and repress the enzymatic activity of the cellular 5'-3' exoribonuclease xrn1, resulting in dramatic changes in the stability of cellular mrnas. we used biochemical assays, virus infections, and transfection of the hcv and bvdv 5' untranslated regions in the absence of other viral gene products to directly demonstrate the existence and mechanism of this novel host-v ... | 2015 | 25747802 |
| to translate, or not to translate: viral and host mrna regulation by interferon-stimulated genes. | type i interferon (ifn) is one of the first lines of cellular defense against viral pathogens. as a result of ifn signaling, a wide array of ifn-stimulated gene (isg) products is upregulated to target different stages of the viral life cycle. we review recent findings implicating a subset of isgs in translational regulation of viral and host mrnas. translation inhibition is mediated either by binding to viral rna or by disrupting physiological interactions or levels of the translation complex co ... | 2015 | 25748385 |