Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
|---|
| chikungunya nsp2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine. | chikungunya virus is the pathogenic alphavirus that causes chikungunya fever in humans. in the last decade millions of cases have been reported around the world from africa to asia to the americas. the alphavirus nsp2 protein is multifunctional and is considered to be pivotal to viral replication, as the nsp2 protease activity is critical for proteolytic processing of the viral polyprotein during replication. classically the alphavirus nsp2 protease is thought to be papain-like with the enzyme r ... | 2015 | 26597768 |
| conformational ensemble of the poliovirus 3cd precursor observed by md simulations and confirmed by saxs: a strategy to expand the viral proteome? | the genomes of rna viruses are relatively small. to overcome the small-size limitation, rna viruses assign distinct functions to the processed viral proteins and their precursors. this is exemplified by poliovirus 3cd protein. 3c protein is a protease and rna-binding protein. 3d protein is an rna-dependent rna polymerase (rdrp). 3cd exhibits unique protease and rna-binding activities relative to 3c and is devoid of rdrp activity. the origin of these differences is unclear, since crystal structur ... | 2015 | 26610545 |
| design, synthesis, and antiviral activity of novel ribonucleosides of 1,2,3-triazolylbenzyl-aminophosphonates. | a novel series of ribonucleosides of 1,2,3-triazolylbenzyl-aminophosphonates was synthesized through the kabachnik-fields reaction using i2 as catalyst followed by copper-catalyzed cycloaddition of the azide-alkyne reaction (cuaac). all structures of the newly prepared compounds were characterized by (1) h nmr, (13) c nmr, and hrms spectra. the structures of 2e, 2f, 3d, and 3g were further confirmed by x-ray diffraction analysis. these compounds were tested against various strains of dna and rna ... | 2015 | 26575425 |
| chikungunya virus replication in salivary glands of the mosquito aedes albopictus. | chikungunya virus (chikv) is an emerging arbovirus transmitted to humans by mosquitoes such as aedes albopictus. to be transmitted, chikv must replicate in the mosquito midgut, then disseminate in the hemocele and infect the salivary glands before being released in saliva. we have developed a standardized protocol to visualize viral particles in the mosquito salivary glands using transmission electron microscopy. here we provide direct evidence for chikv replication and storage in ae. albopictus ... | 2015 | 26593936 |
| pros and cons of antigen-presenting cell targeted tumor vaccines. | in therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. this review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted a ... | 2015 | 26583156 |
| viral interference and persistence in mosquito-borne flaviviruses. | mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. however, the epidemiological impact remains to be determined. mosquito-borne flaviviruses are primarily transmitted through aedes and culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. this establishment requires a balance between virus replication and the ... | 2015 | 26583158 |
| hiv vaccine: recent advances, current roadblocks, and future directions. | hiv/aids is a leading cause of mortality and morbidity worldwide. in spite of successful interventions and treatment protocols, an hiv vaccine would be the ultimate prevention and control strategy. ever since identification of hiv/aids, there have been meticulous efforts for vaccine development. the specific aim of this paper is to review recent vaccine efficacy trials and associated advancements and discuss the current challenges and future directions. recombinant dna technologies greatly facil ... | 2015 | 26579546 |
| parp9-dtx3l ubiquitin ligase targets host histone h2bj and viral 3c protease to enhance interferon signaling and control viral infection. | enhancing the response to interferon could offer an immunological advantage to the host. in support of this concept, we used a modified form of the transcription factor stat1 to achieve hyper-responsiveness to interferon without toxicity and markedly improve antiviral function in transgenic mice and transduced human cells. we found that the improvement depended on expression of a parp9-dtx3l complex with distinct domains for interaction with stat1 and for activity as an e3 ubiquitin ligase that ... | 2015 | 26479788 |
| serological evidence of chikungunya virus among acute febrile patients in southern mozambique. | in the last two decades, chikungunya virus (chikv) has rapidly expanded to several geographical areas, causing frequent outbreaks in sub-saharan africa, south east asia, south america, and europe. therefore, the disease remains heavily neglected in mozambique, and no recent study has been conducted. | 2015 | 26473605 |
| mouse superkiller-2-like helicase ddx60 is dispensable for type i ifn induction and immunity to multiple viruses. | ifn-α/β allow cells to fight virus infection by inducing the expression of many genes that encode effectors of antiviral defense. one of these, the ski2-like dexh-box helicase ddx60, was recently implicated in resistance of human cells to hepatitis c virus, as well as in induction of ifn-α/β by retinoic acid inducible gene 1-like receptors (rlrs) that detect the presence of rna viruses in a cell-intrinsic manner. here, we sought to investigate the role of ddx60 in ifn-α/β induction and in resist ... | 2015 | 26457795 |
| simultaneous determination of sample thickness, tilt, and electron mean free path using tomographic tilt images based on beer-lambert law. | cryo-electron tomography (cryo-et) is an emerging technique that can elucidate the architecture of macromolecular complexes and cellular ultrastructure in a near-native state. some important sample parameters, such as thickness and tilt, are needed for 3-d reconstruction. however, these parameters can currently only be determined using trial 3-d reconstructions. accurate electron mean free path plays a significant role in modeling image formation process essential for simulation of electron micr ... | 2015 | 26433027 |
| hur and ago2 bind the internal ribosome entry site of enterovirus 71 and promote virus translation and replication. | ev71 (enterovirus 71) rna contains an internal ribosomal entry site (ires) that directs cap-independent initiation of translation. ires-dependent translation requires the host's translation initiation factors and ires-associated trans-acting factors (itafs). we reported recently that mrna decay factor auf1 is a negative-acting itaf that binds ires stem-loop ii. we also reported that the small rna-processing enzyme dicer produces at least four small rnas (vsrnas) from the ev71 ires. one of these, ... | 2015 | 26451954 |
| serum levels of inflammatory cytokines in rift valley fever patients are indicative of severe disease. | rift valley fever (rvf) is a mosquito-borne viral zoonosis affecting domestic and wild ruminants, camels and humans. outbreaks of rvf are characterized by a sudden onset of abortions and high mortality amongst domestic ruminants. humans develop disease ranging from a mild flu-like illness to more severe complications including hemorrhagic syndrome, ocular and neurological lesions and death. during the rvf outbreak in south africa in 2010/11, a total of 278 human cases were laboratory confirmed, ... | 2015 | 26437779 |
| virus-based nanoparticles as versatile nanomachines. | nanoscale engineering is revolutionizing the way we prevent, detect, and treat diseases. viruses have played a special role in these developments because they can function as prefabricated nanoscaffolds that have unique properties and are easily modified. the interiors of virus particles can encapsulate and protect sensitive compounds, while the exteriors can be altered to display large and small molecules in precisely defined arrays. these properties of viruses, along with their innate biocompa ... | 2015 | 26958921 |
| intracellular mono-adp-ribosylation in signaling and disease. | a key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. moreover detailed knowledge about these mechanisms and pathways helps to elucidate ... | 2015 | 26426055 |
| infectious bronchitis coronavirus inhibits stat1 signaling and requires accessory proteins for resistance to type i interferon activity. | the innate immune response is the first line of defense against viruses, and type i interferon (ifn) is a critical component of this response. similar to other viruses, the gammacoronavirus infectious bronchitis virus (ibv) has evolved under evolutionary pressure to evade and counteract the ifn response to enable its survival. previously, we reported that ibv induces a delayed activation of the ifn response. in the present work, we describe the resistance of ibv to ifn and the potential role of ... | 2015 | 26401035 |
| antiviral potential of algae polysaccharides isolated from marine sources: a review. | from food to fertilizer, algal derived products are largely employed in assorted industries, including agricultural, biomedical, food, and pharmaceutical industries. among different chemical compositions isolated from algae, polysaccharides are the most well-established compounds, which were subjected to a variety of studies due to extensive bioactivities. over the past few decades, the promising results for antiviral potential of algae-derived polysaccharides have advocated them as inordinate c ... | 2015 | 26484353 |
| colorimetric detection of dengue by single tube reverse-transcription-loop-mediated isothermal amplification. | dengue is usually diagnosed by isolation of the virus, serology or molecular diagnostic methods. several commercial kits for the diagnosis of dengue are existing, but concerns have arisen regarding to the affordability and performance characteristics of these kits. hence, the loop-mediated isothermal amplification (lamp) is potentially ideal to be used especially in resource limited environments. serum was collected from healthy donors and patients diagnosed with dengue infection. rna extracted ... | 2015 | 26384248 |
| in vivo two-photon imaging of dendritic spines in marmoset neocortex(1,2,3). | two-photon microscopy in combination with a technique involving the artificial expression of fluorescent protein has enabled the direct observation of dendritic spines in living brains. however, the application of this method to primate brains has been hindered by the lack of appropriate labeling techniques for visualizing dendritic spines. here, we developed an adeno-associated virus vector-based fluorescent protein expression system for visualizing dendritic spines in vivo in the marmoset neoc ... | 2015 | 26465000 |
| retargeting oncolytic vesicular stomatitis virus to human t-cell lymphotropic virus type 1-associated adult t-cell leukemia. | adult t cell leukemia/lymphoma (atl) is an aggressive cancer of cd4/cd25(+) t lymphocytes, the etiological agent of which is human t-cell lymphotropic virus type 1 (htlv-1). atl is highly refractory to current therapies, making the development of new treatments a high priority. oncolytic viruses such as vesicular stomatitis virus (vsv) are being considered as anticancer agents since they readily infect transformed cells compared to normal cells, the former appearing to exhibit defective innate i ... | 2015 | 26378177 |
| regulation of cell death by iaps and their antagonists. | inhibitors of apoptosis (iaps) family of genes encode baculovirus iap-repeat domain-containing proteins with antiapoptotic function. these proteins also contain ring or ubc domains and act by binding to major proapoptotic factors and ubiquitylating them. high levels of iaps inhibit caspase-mediated apoptosis. for these cells to undergo apoptosis, iap function must be neutralized by iap-antagonists. mammalian iap knockouts do not exhibit obvious developmental phenotypes, but the cells are more se ... | 2015 | 26431568 |
| fiat luc: bioluminescence imaging reveals in vivo viral replication dynamics. | 2015 | 26356297 | |
| kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 1 interacts with a member of the interferon-stimulated gene 15 pathway. | kaposi's sarcoma-associated herpesvirus (kshv) is a gammaherpesvirus known to establish lifelong latency in the human host. we and others have previously shown that three kshv homologs of cellular interferon regulatory factors (irfs), known as viral irfs (virfs), participate in evasion of the host interferon (ifn) response. we report that virf1 interacts with the cellular interferon-stimulated gene 15 (isg15) e3 ligase, herc5, in the context of toll-like receptor 3 (tlr3) activation and ifn indu ... | 2015 | 26355087 |
| hur displaces polypyrimidine tract binding protein to facilitate la binding to the 3' untranslated region and enhances hepatitis c virus replication. | hur is a ubiquitous, rna binding protein that influences the stability and translation of several cellular mrnas. here, we report a novel role for hur, as a regulator of proteins assembling at the 3' untranslated region (utr) of viral rna in the context of hepatitis c virus (hcv) infection. hur relocalizes from the nucleus to the cytoplasm upon hcv infection, interacts with the viral polymerase (ns5b), and gets redistributed into compartments of viral rna synthesis. depletion in hur levels leads ... | 2015 | 26339049 |
| structural and functional characterization of anti-a33 antibodies reveal a potent cross-species orthopoxviruses neutralizer. | vaccinia virus a33 is an extracellular enveloped virus (eev)-specific type ii membrane glycoprotein that is essential for efficient eev formation and long-range viral spread within the host. a33 is a target for neutralizing antibody responses against eev. in this study, we produced seven murine anti-a33 monoclonal antibodies (mabs) by immunizing mice with live vacv, followed by boosting with the soluble a33 homodimeric ectodomain. five a33 specific mabs were capable of neutralizing eev in the pr ... | 2015 | 26325270 |
| selective effects of pde10a inhibitors on striatopallidal neurons require phosphatase inhibition by darpp-32(1,2,3). | type 10a phosphodiesterase (pde10a) is highly expressed in the striatum, in striatonigral and striatopallidal medium-sized spiny neurons (msns), which express d1 and d2 dopamine receptors, respectively. pde10a inhibitors have pharmacological and behavioral effects suggesting an antipsychotic profile, but the cellular bases of these effects are unclear. we analyzed the effects of pde10a inhibition in vivo by immunohistochemistry, and imaged camp, camp-dependent protein kinase a (pka), and cgmp si ... | 2015 | 26465004 |
| flavivirus sfrna suppresses antiviral rna interference in cultured cells and mosquitoes and directly interacts with the rnai machinery. | productive arbovirus infections require mechanisms to suppress or circumvent the cellular rna interference (rnai) pathway, a major antiviral response in mosquitoes. in this study, we demonstrate that two flaviviruses, dengue virus and kunjin virus, significantly repress sirna-mediated rnai in infected human cells as well as during infection of the mosquito vector culex quinquefasciatus. arthropod-borne flaviviruses generate a small structured non-coding rna from the viral 3' utr referred to as s ... | 2015 | 26331679 |
| cd8 t-cell priming upon mrna vaccination is restricted to bone-marrow-derived antigen-presenting cells and may involve antigen transfer from myocytes. | self-amplifying mrnas (sam(®) ) are a novel class of nucleic acid vaccines, delivered by a non-viral delivery system. they are effective at eliciting potent and protective immune responses and are being developed as a platform technology with potential to be used for a broad range of targets. however, their mechanism of action has not been fully elucidated. to date, no evidence of in vivo transduction of professional antigen-presenting cells (apcs) by sam vector has been reported, while the anti ... | 2015 | 26173587 |
| detection of persistent chikungunya virus rna but not infectious virus in experimental vertical transmission in aedes aegypti from malaysia. | vertical transmission may contribute to the maintenance of arthropod-borne viruses, but its existence in chikungunya virus (chikv) is unclear. experimental vertical transmission of infectious clones of chikv in aedes aegypti mosquitoes from malaysia was investigated. eggs and adult progeny from the second gonotrophic cycles of infected parental mosquitoes were tested. using polymerase chain reaction (pcr), 56.3% of pooled eggs and 10% of adult progeny had detectable chikv rna, but no samples had ... | 2015 | 26598564 |
| structural studies of chikungunya virus-like particles complexed with human antibodies: neutralization and cell-to-cell transmission. | chikungunya virus is a positive-stranded rna alphavirus. structures of chikungunya virus-like particles in complex with strongly neutralizing antibody fab fragments (8b10 and 5f10) were determined using cryo-electron microscopy and x-ray crystallography. by fitting the crystallographically determined structures of these fab fragments into the cryo-electron density maps, we show that fab fragments of antibody 8b10 extend radially from the viral surface and block receptor binding on the e2 glycopr ... | 2015 | 26537684 |
| trehalose, an mtor-independent inducer of autophagy, inhibits human cytomegalovirus infection in multiple cell types. | human cytomegalovirus (hcmv) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. previous studies have shown that the induction of autophagy can inhibit the replication of several different types of dna and rna viruses. the goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of hcmv. most prior studies have used agents that induce autop ... | 2015 | 26559848 |
| the interferon-stimulated gene ifi27l2a restricts west nile virus infection and pathogenesis in a cell-type- and region-specific manner. | the mammalian host responds to viral infections by inducing expression of hundreds of interferon-stimulated genes (isgs). while the functional significance of many isgs has yet to be determined, their cell type and temporal nature of expression suggest unique activities against specific pathogens. using a combination of ectopic expression and gene silencing approaches in cell culture, we previously identified ifi27l2a as a candidate antiviral isg within neuronal subsets of the central nervous sy ... | 2015 | 26699642 |
| low-fidelity polymerases of alphaviruses recombine at higher rates to overproduce defective interfering particles. | low-fidelity rna-dependent rna polymerases for many rna virus mutators have been shown to confer attenuated phenotypes, presumably due to increased mutation rates. additionally, for many rna viruses, replication to high titers results in the production of defective interfering particles (dis) that also attenuate infection. we hypothesized that fidelity, recombination, and di production are tightly linked. we show that a sindbis virus mutator replicating at a high multiplicity of infection manife ... | 2015 | 26676773 |
| rapid selection against arbovirus-induced apoptosis during infection of a mosquito vector. | millions of people are infected each year by arboviruses (arthropod-borne viruses) such as chikungunya, dengue, and west nile viruses, yet for reasons that are largely unknown, only a relatively small number of mosquito species are able to transmit arboviruses. understanding the complex factors that determine vector competence could facilitate strategies for controlling arbovirus infections. apoptosis is a potential antiviral defense response that has been shown to be important in other virus-ho ... | 2015 | 25713358 |
| the α2,3-sialyltransferase encoded by myxoma virus is a virulence factor that contributes to immunosuppression. | myxoma virus (myxv) induces a lethal disease called myxomatosis in european rabbits. myxv is one of the rare viruses that encodes an α2,3-sialyltransferase through its m138l gene. in this study, we showed that although the absence of the enzyme was not associated with any in vitro deficit, the m138l deficient strains are highly attenuated in vivo. indeed, while all rabbits infected with the parental and the revertant strains died within 9 days post-infection from severe myxomatosis, all but one ... | 2015 | 25705900 |
| the sd1 subdomain of venezuelan equine encephalitis virus capsid protein plays a critical role in nucleocapsid and particle assembly. | venezuelan equine encephalitis virus (veev) is an important human and animal pathogen, for which no safe and efficient vaccines or therapeutic means have been developed. viral particle assembly and budding processes represent potential targets for therapeutic intervention. however, our understanding of the mechanistic process of veev assembly, rna encapsidation, and the roles of different capsid-specific domains in these events remain to be described. the results of this new study demonstrate th ... | 2015 | 26656680 |
| trisubstituted thieno[3,2-b]pyrrole 5-carboxamides as potent inhibitors of alphaviruses. | chikungunya virus (chikv) is a re-emerging vector-borne alphavirus and is transmitted to humans by aedes mosquitoes. despite the re-emergence of chikv as an epidemic threat, there is no approved effective antiviral treatment currently available for chikv. herein, we report the synthesis and structure-activity relationship studies of a class of thieno[3,2-b]pyrroles and the discovery of a trisubstituted thieno[3,2-b]pyrrole 5-carboxamide 15c that exhibits potent inhibitory activity against in vit ... | 2015 | 26540338 |
| suramin inhibits chikungunya virus replication through multiple mechanisms. | chikungunya virus (chikv) is a mosquito-borne alphavirus that causes severe and often persistent arthritis. in recent years, millions of people have been infected with this virus for which registered antivirals are still lacking. using our recently established in vitro assay, we discovered that the approved anti-parasitic drug suramin inhibits chikv rna synthesis (ic50 of ∼5μm). the compound inhibited replication of various chikv isolates in cell culture with an ec50 of ∼80μm (cc50>5mm) and was ... | 2015 | 26112648 |
| antiviral activity of flexibilane and tigliane diterpenoids from stillingia lineata. | in an effort to identify new potent and selective inhibitors of chikungunya virus and hiv-1 and hiv-2 virus replication, the endemic mascarene species stillingia lineata was investigated. lc/ms and bioassay-guided purification of the etoac leaf extract using a chikungunya virus-cell-based assay led to the isolation of six new (4-9) and three known (1-3) tonantzitlolones possessing the rare c20-flexibilane skeleton, along with tonantzitloic acid (10), a new linear diterpenoid, and three new (11, ... | 2015 | 25946116 |
| sphingolipids in viral infection. | viruses exploit membranes and their components such as sphingolipids in all steps of their life cycle including attachment and membrane fusion, intracellular transport, replication, protein sorting and budding. examples for sphingolipid-dependent virus entry are found for: human immunodeficiency virus (hiv), which besides its protein receptors also interacts with glycosphingolipids (gsls); rhinovirus, which promotes the formation of ceramide-enriched platforms and endocytosis; or measles virus ( ... | 2015 | 25525752 |
| 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 |
| antiviral activities of whey proteins. | milk contains an array of proteins with useful bioactivities. many milk proteins encompassing native or chemically modified casein, lactoferrin, alpha-lactalbumin, and beta-lactoglobulin demonstrated antiviral activities. casein and alpha-lactalbumin gained anti-hiv activity after modification with 3-hydroxyphthalic anhydride. many milk proteins inhibited hiv reverse transcriptase. bovine glycolactin, angiogenin-1, lactogenin, casein, alpha-lactalbumin, beta-lactoglobulin, bovine lactoferrampin, ... | 2015 | 26198883 |
| enveloped virus flocculation and removal in osmolyte solutions. | our ability to reduce infectious disease burden throughout the world has been greatly improved by the creation of vaccines. however, worldwide immunization rates are low. the two most likely reasons are the lack of sufficient distribution in underdeveloped countries and the high cost of vaccine products. the high costs are due to the difficulties of manufacturing individual vaccine products with specialized purification trains. in this study, we propose to use virus flocculation in osmolytes, fo ... | 2015 | 25865274 |
| semliki forest virus and sindbis virus, but not vaccinia virus, require glycolysis for optimal replication. | viruses are obligate intracellular pathogens which rely on the cell's machinery to produce the energy and macromolecules required for replication. infection is associated with a modified metabolic profile and one pathway which can be modified is glycolysis. in this study, we investigated if the glycolysis pathway is required for alphavirus replication. pre-treatment of vero cells with three different glycolysis inhibitors (2-deoxyglucose, lonidamine and oxamate) resulted in a significant reducti ... | 2015 | 26297236 |
| virus adsorption of water-stable quaternized chitosan nanofibers. | the burden of unsafe drinking water is responsible for millions of deaths each year. to relieve this burden, we are in search of an inexpensive material that can adsorb pathogens from drinking water. in this pursuit, we have studied the natural carbohydrate, chitosan. to impart virus removal features, chitosan has been functionalized with a quaternary amine to form quaternized chitosan n-[(2-hydroxyl-3-trimethylammonium) propyl] chitosan (htcc). htcc can be electrospun into nanofibers with the n ... | 2014 | 24561959 |
| [complete genome characterization of the kyzylagach virus (kyzv) (togaviridae, alphavirus, sindbis serogroup) isolated from mosquitoes culex modestus ficalbi, 1889 (culicinae) collected in a colony of herons (ardeidae leach, 1820) in azerbaijan]. | complete genome sequencing of the kyzylagach virus (kyzv) leiv-65a strain isolated from the culex modestus ficalbi, 1889 (culicinae), which was collected in the colony of the ardeidae leach, 1820 birds on the coast of caspian sea, kyzyl-agach bay, in the southern part of azerbaijan, was carried out. kyzv has high homology (about 99%) with the chinese xj-160 strain of the sindbis virus (sinv) isolated from anopheles sp. in xinjiang uyghur autonomic region (north-eastern china). homologies of kyzv ... | 2014 | 25895208 |
| effect of mixed infections of sindbis and la crosse viruses on replication of each virus in vitro. | mixed viral infections are ubiquitous in natural populations and may have significant but unpredictable biological and epidemiological consequences. these infections may be acquired simultaneously (coinfection) or result from two single infections at different time intervals (superinfection). this study investigated the effect of mixed infections of two mosquito-borne viruses, sindbis (sinv) and la crosse (lacv), on the replication of each virus in vertebrate baby hamster kidney (bhk) and invert ... | 2014 | 24463260 |
| antiviral activity of lanatoside c against dengue virus infection. | dengue infection poses a serious threat globally due to its recent rapid spread and rise in incidence. currently, there is no approved vaccine or effective antiviral drug for dengue virus infection. in response to the urgent need for the development of an effective antiviral for dengue virus, the us drug collection library was screened in this study to identify compounds with anti-dengue activities. lanatoside c, an fda approved cardiac glycoside was identified as a candidate anti-dengue compoun ... | 2014 | 25251726 |
| jatrophane diterpenes as inhibitors of chikungunya virus replication: structure-activity relationship and discovery of a potent lead. | bioassay-guided purification of an etoac extract of the whole plant of euphorbia amygdaloides ssp. semiperfoliata using a chikungunya virus-cell-based assay led to the isolation of six new (1-4, 9, and 10) and six known (5-7, 8, 11, and 12) jatrophane esters. their planar structures and relative configurations were determined by extensive spectroscopic analysis, and their absolute configurations by x-ray analysis. these compounds were investigated for selective antiviral activity against chikung ... | 2014 | 24926807 |
| the role of viral genomic rna and nucleocapsid protein in the autophagic clearance of hantavirus glycoprotein gn. | hantaviruses have tri-segmented negative sense rna genome. the viral m-segment rna encodes a glycoprotein precursor (gpc), which is cleaved into two glycoprotein molecules gn and gc that form spikes on the viral envelope. we previously reported that gn is degraded shortly after synthesis by the host autophagy machinery. however, gn being an important integral component of the virion, must escape degradation during the packaging and assembly stage of virus replication cycle. the mechanism regulat ... | 2014 | 24412713 |
| sorting through the roles of beclin 1 in microglia and neurodegeneration. | beclin 1 has a well-established role in regulating autophagy, a cellular degradation pathway. although the yeast ortholog of beclin 1 (atg6/vps30) was discovered to also regulate vacuolar protein sorting nearly 30 years ago, the varied functions of beclin 1 in mammalian cells are only beginning to be sorted out. we recently described a role for beclin 1 in regulating recycling of phagocytic receptors in microglia, a function analogous to that of its yeast ortholog. microglia lacking beclin 1 hav ... | 2014 | 24385262 |
| fusion-related host proteins are actively regulated by na during influenza infection as revealed by quantitative proteomics analysis. | three recombinant influenza a viruses with different neuraminidases (nas) in the background of a/pr/8/34 (pr8), named rpr8-h5n1na, rpr8-h9n2na, and rpr8-h1n1na, derived from h5n1, h9n2, h1n1 (swine) viruses, respectively, were constructed. we performed a quantitative proteomics analysis to investigate differential protein expression in madin-darby canine kidney (mdck) cells infected with recombinant and wild-type influenza viruses to determine whether na replacement would alter host cell gene ex ... | 2014 | 25153908 |
| assembly and maturation of a t = 4 quasi-equivalent virus is guided by electrostatic and mechanical forces. | nudaurelia capensis w virus (nωv) is a eukaryotic rna virus that is well suited for the study of virus maturation. the virus initially assembles at ph 7.6 into a marginally stable 480-å procapsid formed by 240 copies of a single type of protein subunit. during maturation, which occurs during apoptosis at ph 5.0, electrostatic forces guide subunit trajectories into a robust 410-å virion that is buttressed by subunit associated molecular switches. we discuss the competing factors in the virus caps ... | 2014 | 25153346 |
| a cationic nanoemulsion for the delivery of next-generation rna vaccines. | nucleic acid-based vaccines such as viral vectors, plasmid dna, and mrna are being developed as a means to address a number of unmet medical needs that current vaccine technologies have been unable to address. here, we describe a cationic nanoemulsion (cne) delivery system developed to deliver a self-amplifying mrna vaccine. this nonviral delivery system is based on novartis's proprietary adjuvant mf59, which has an established clinical safety profile and is well tolerated in children, adults, a ... | 2014 | 25027661 |
| computational identification of dengue virus microrna-like structures and their cellular targets. | micrornas (mirnas) are small, noncoding rna molecules that regulate transcriptional and posttranscriptional gene regulation of the cell. experimental evidence shows that mirnas have a direct role in different cellular processes, such as immune function, apoptosis, and tumorigenesis. in a viral infection context, mirnas have been connected with the interplay between host and pathogen, occupying a major role in pathogenesis. while numerous viral mirnas from dna viruses have been identified, charac ... | 2014 | 25210446 |
| beth levine receives the 2014 asci/stanley j. korsmeyer award. | 2014 | 24691475 | |
| the role of hur in the post-transcriptional regulation of interleukin-3 in t cells. | human interleukin-3 (il-3) is a lymphokine member of a class of transiently expressed mrnas harboring adenosine/uridine-rich elements (are) in their 3' untranslated regions (3'-utrs). the regulatory effects of ares are often mediated by specific are-binding proteins (are-bps). in this report, we show that the human il-3 3'-utr plays a post-transcriptional regulation role in two human transformed cell lines. more specifically, we demonstrate that the hil-3 3'-utr represses the translation of a lu ... | 2014 | 24658545 |
| quantitative phosphoproteomics unravels biased phosphorylation of serotonin 2a receptor at ser280 by hallucinogenic versus nonhallucinogenic agonists. | the serotonin 5-ht(2a) receptor is a primary target of psychedelic hallucinogens such as lysergic acid diethylamine, mescaline, and psilocybin, which reproduce some of the core symptoms of schizophrenia. an incompletely resolved paradox is that only some 5-ht(2a) receptor agonists exhibit hallucinogenic activity, whereas structurally related agonists with comparable affinity and activity lack such a psychoactive activity. using a strategy combining stable isotope labeling by amino acids in cell ... | 2014 | 24637012 |
| vectorology and factor delivery in induced pluripotent stem cell reprogramming. | induced pluripotent stem cell (ipsc) reprogramming requires sustained expression of multiple reprogramming factors for a limited period of time (10-30 days). conventional ipsc reprogramming was achieved using lentiviral or simple retroviral vectors. retroviral reprogramming has flaws of insertional mutagenesis, uncontrolled silencing, residual expression and re-activation of transgenes, and immunogenicity. to overcome these issues, various technologies were explored, including adenoviral vectors ... | 2014 | 24625220 |
| plant virus expression vector development: new perspectives. | plant made biologics have elicited much attention over recent years for their potential in assisting those in developing countries who have poor access to modern medicine. additional applications such as the stockpiling of vaccines against pandemic infectious diseases or potential biological warfare agents are also under investigation. plant virus expression vectors represent a technology that enables high levels of pharmaceutical proteins to be produced in a very short period of time. recent ad ... | 2014 | 24745025 |
| autophagy in plasma cell pathophysiology. | plasma cells (pcs) are the effectors responsible for antibody (ab)-mediated immunity. they differentiate from b lymphocytes through a complete remodeling of their original structure and function. stress is a constitutive element of pc differentiation. macroautophagy, conventionally referred to as autophagy, is a conserved lysosomal recycling strategy that integrates cellular metabolism and enables adaptation to stress. in metazoa, autophagy plays diverse roles in cell differentiation. recently, ... | 2014 | 24659989 |
| two alternative ways of start site selection in human norovirus reinitiation of translation. | the calicivirus minor capsid protein vp2 is expressed via termination/reinitiation. this process depends on an upstream sequence element denoted termination upstream ribosomal binding site (turbs). we have shown for feline calicivirus and rabbit hemorrhagic disease virus that the turbs contains three sequence motifs essential for reinitiation. motif 1 is conserved among caliciviruses and is complementary to a sequence in the 18 s rrna leading to the model that hybridization between motif 1 and 1 ... | 2014 | 24599949 |
| more novel hantaviruses and diversifying reservoir hosts--time for development of reservoir-derived cell culture models? | due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus hantavirus. furthermore, reservoir host species are increasingly recognized besides representatives of the order rodentia, now including members of the mammalian orders soricomorpha/eulipotyphla and chiroptera. despite the great interest created by emerging zoonotic viruses, there is still a gross lack of in vitro models, which reflect the exclusive host adaptation of mo ... | 2014 | 24576845 |
| critical role of interferon-α constitutively produced in human hepatocytes in response to rna virus infection. | several viruses are known to infect human liver and cause the hepatitis, but the interferon (ifn) response, a first-line defense against viral infection, of virus-infected hepatocytes is not clearly defined yet. we investigated innate immune system against rna viral infection in immortalized human hepatocytes (hus-e/2 cells), as the cells showed similar early innate immune responses to primary human hepatocytes (phh). the low-level constitutive expression of ifn-α1 gene, but not ifn-β and ifn-λ, ... | 2014 | 24587086 |
| dynamic survey of mitochondria by ubiquitin. | ubiquitin is a post-translational modifier with proteolytic and non-proteolytic roles in many biological processes. at mitochondria, it performs regulatory homeostatic functions and contributes to mitochondrial quality control. ubiquitin is essential for mitochondrial fusion, regulates mitochondria-er contacts, and participates in maternal mtdna inheritance. under stress, mitochondrial dysfunction induces ubiquitin-dependent responses that involve mitochondrial proteome remodeling and culminate ... | 2014 | 24569520 |
| the yellow fever 17d virus as a platform for new live attenuated vaccines. | the live-attenuated yellow fever 17d virus is one of the most outstanding human vaccines ever developed. it induces efficacious immune responses at a low production cost with a well-established manufacture process. these advantages make the yf17d virus attractive as a vector for the development of new vaccines. at the beginning of vector development studies, yf17d was genetically manipulated to express other flavivirus prm and e proteins, components of the viral envelope. while these 17d recombi ... | 2014 | 24553128 |
| the role of ikkβ in venezuelan equine encephalitis virus infection. | venezuelan equine encephalitis virus (veev) belongs to the genus alphavirus, family togaviridae. veev infection is characterized by extensive inflammation and studies from other laboratories implicated an involvement of the nf-κb cascade in the in vivo pathology. initial studies indicated that at early time points of veev infection, the nf-κb complex was activated in cells infected with the tc-83 strain of veev. one upstream kinase that contributes to the phosphorylation of p65 is the ikkβ compo ... | 2014 | 24586253 |
| genome-wide rnai screen identifies broadly-acting host factors that inhibit arbovirus infection. | vector-borne viruses are an important class of emerging and re-emerging pathogens; thus, an improved understanding of the cellular factors that modulate infection in their respective vertebrate and insect hosts may aid control efforts. in particular, cell-intrinsic antiviral pathways restrict vector-borne viruses including the type i interferon response in vertebrates and the rna interference (rnai) pathway in insects. however, it is likely that additional cell-intrinsic mechanisms exist to limi ... | 2014 | 24550726 |
| interferon-stimulated genes: a complex web of host defenses. | interferon-stimulated gene (isg) products take on a number of diverse roles. collectively, they are highly effective at resisting and controlling pathogens. in this review, we begin by introducing interferon (ifn) and the jak-stat signaling pathway to highlight features that impact isg production. next, we describe ways in which isgs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the jak-stat pathway. several isgs that directly inhibit virus infection ... | 2014 | 24555472 |
| a gammaherpesvirus bcl-2 ortholog blocks b cell receptor-mediated apoptosis and promotes the survival of developing b cells in vivo. | gammaherpesviruses such as epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv, hhv-8) establish lifelong latency in their hosts and are associated with the development of several types of malignancies, including a subset of b cell lymphomas. these viruses are thought to co-opt the process of b cell differentiation to latently infect a fraction of circulating memory b cells, resulting in the establishment of a stable latency setpoint. however, little is known about how thi ... | 2014 | 24516386 |
| microrna-like viral small rna from dengue virus 2 autoregulates its replication in mosquito cells. | micrornas (mirnas) are small regulatory rnas that play significant roles in most cellular processes. in the seemingly endless arms race between hosts and pathogens, viruses also encode mirnas that facilitate successful infection. in search of functional mirnas or viral small rnas (vsrnas) encoded by dengue virus (denv), deep sequencing data of virus-infected aedes aegypti mosquitoes were used. from six vsrnas, with candidate stem-loop structures in the 5' and 3' untranslated regions of the viral ... | 2014 | 24550303 |
| design, synthesis, antiviral and cytotoxic evaluation of novel acyclic phosphonate nucleotide analogues with a 5,6-dihydro-1h-[1,2,3]triazolo[4,5-d]pyridazine-4,7-dione system. | a series of diethyl 2-(4,5-dimethoxycarbonyl-1h-1,2,3-triazol-1-yl)alkylphosphonates was synthesised from ω-azidoalkylphosphonates and dimethyl acetylenedicarboxylate and was further transformed into the respective diamides, dihydrazides, and 5,6-dihydro-1h-[1,2,3]triazolo[4,5-d]pyridazine-4,7-diones as phosphonate analogues of acyclic nucleosides having nucleobases replaced with substituted 1,2,3-triazoles. all compounds containing p-c-c-triazole or p-c-c-ch2-triazole moieties exist in single c ... | 2014 | 26166892 |
| distinctive effects of the cellular inhibitor of apoptosis protein c-iap2 through stabilization by xiap in glioblastoma multiforme cells. | inhibitor of apoptosis proteins (iaps) are extensively involved in nfκb signaling pathways. regulation of c-iap2 turnover by other proteins was investigated in glioblastoma multiforme (gbm) cells in the present study. when overexpressed, x-linked iap (xiap) enhanced expression of ectopic c-iap2, but not c-iap1, and endogenous c-iap2 levels were reduced once xiap expression was silenced. tnfα stimulation substantially increased c-iap2 expression, and this upregulation was impaired by suppression ... | 2014 | 24552816 |
| targeting γ-herpesvirus 68 bcl-2-mediated down-regulation of autophagy. | γ-herpesviruses (γhvs) are common human pathogens that encode homologs of the anti-apoptotic cellular bcl-2 proteins, which are critical to viral reactivation and oncogenic transformation. the murine γhv68 provides a tractable in vivo model for understanding general features of these important human pathogens. bcl-xl, a cellular bcl-2 homolog, and the murine γhv68 bcl-2 homolog, m11, both bind to a bh3 domain within the key autophagy effector beclin 1 with comparable affinities, resulting in the ... | 2014 | 24443581 |
| alphavirus mutator variants present host-specific defects and attenuation in mammalian and insect models. | arboviruses cycle through both vertebrates and invertebrates, which requires them to adapt to disparate hosts while maintaining genetic integrity during genome replication. to study the genetic mechanisms and determinants of these processes, we use chikungunya virus (chikv), a re-emerging human pathogen transmitted by the aedes mosquito. we previously isolated a high fidelity (or antimutator) polymerase variant, c483y, which had decreased fitness in both mammalian and mosquito hosts, suggesting ... | 2014 | 24453971 |
| from scourge to cure: tumour-selective viral pathogenesis as a new strategy against cancer. | tumour mutations corrupt cellular pathways, and accumulate to disrupt, dysregulate, and ultimately avoid mechanisms of cellular control. yet the very changes that tumour cells undergo to secure their own growth success also render them susceptible to viral infection. enhanced availability of surface receptors, disruption of antiviral sensing, elevated metabolic activity, disengagement of cell cycle controls, hyperactivation of mitogenic pathways, and apoptotic avoidance all render the malignant ... | 2014 | 24453963 |
| differential regulation of gabab receptor trafficking by different modes of n-methyl-d-aspartate (nmda) receptor signaling. | inhibitory gabab receptors (gababrs) can down-regulate most excitatory synapses in the cns by reducing postsynaptic excitability. functional gababrs are heterodimers of gabab1 and gabab2 subunits and here we show that the trafficking and surface expression of gababrs is differentially regulated by synaptic or pathophysiological activation of nmda receptors (nmdars). activation of synaptic nmdars using a chemltp protocol increases gababr recycling and surface expression. in contrast, excitotoxic ... | 2014 | 24425870 |
| viruses and rna interference: issues and controversies. | the question of whether any mammalian cells are able to mount an effective rna interference-mediated antiviral innate immune response has remained highly controversial. in this gem, i review recent data addressing this important issue and propose a testable hypothesis that can explain many of the apparently contradictory results published in this area of research. | 2014 | 25210170 |
| interleukin 10 modulation of pathogenic th17 cells during fatal alphavirus encephalomyelitis. | mosquito-borne alphaviruses are important causes of epidemic encephalomyelitis. neuronal cell death during fatal alphavirus encephalomyelitis is immune-mediated; however, the types of cells involved and their regulation have not been determined. we show that the virus-induced inflammatory response was accompanied by production of the regulatory cytokine il-10, and in the absence of il-10, paralytic disease occurred earlier and mice died faster. to determine the reason for accelerated disease in ... | 2014 | 25362048 |
| a cytoplasmic rna virus generates functional viral small rnas and regulates viral ires activity in mammalian cells. | the roles of virus-derived small rnas (vsrnas) have been studied in plants and insects. however, the generation and function of small rnas from cytoplasmic rna viruses in mammalian cells remain unexplored. this study describes four vsrnas that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. viral infection produced substantial levels (>10(5) copy numbers per cell) of vsrna1, one of the four vsrnas. we also demonstrated that dicer is involved in ... | 2014 | 25352551 |
| cellular responses to sindbis virus infection of neural progenitors derived from human embryonic stem cells. | sindbis virus (sinv) causes age-dependent encephalitis in mice, and therefore serves as a model to study viral encephalitis. sinv is used as a vector for the delivery of genes into selected neural stem cell lines; however, the toxicity and side effects of this vector have rarely been discussed. in this context, we investigated the cellular responses of human embryonic stem cell (hescs) derived neural progenitors (hnpcs) to sinv infection by assessing susceptibility of the cells to sinv infection ... | 2014 | 25343994 |
| putative novel lineage of west nile virus in uranotaenia unguiculata mosquito, hungary. | west nile virus (wnv) is an increasing public health concern in europe with numerous human cases. a total of 23,029 female mosquitoes were tested for a variety of mosquito-borne flaviviruses and orthobunyaviruses supposedly endemic in southern transdanubia, hungary, in the frames of a large-scale surveillance between 2011 and 2013. wnv nucleic acid was detected in a single pool containing uranotaenia unguiculata mosquitoes. sequence- and phylogenetic analyses for two different regions (ns5 and e ... | 2014 | 25674630 |
| arboviral bottlenecks and challenges to maintaining diversity and fitness during mosquito transmission. | the term arbovirus denotes viruses that are transmitted by arthropods, such as ticks, mosquitoes, and other biting arthropods. the infection of these vectors produces a certain set of evolutionary pressures on the virus; involving migration from the midgut, where the blood meal containing the virus is processed, to the salivary glands, in order to transmit the virus to the next host. during this process the virus is subject to numerous bottlenecks, stochastic events that significantly reduce the ... | 2014 | 25341663 |
| ribosomal readthrough at a short uga stop codon context triggers dual localization of metabolic enzymes in fungi and animals. | translation of mrna into a polypeptide chain is a highly accurate process. many prokaryotic and eukaryotic viruses, however, use leaky termination of translation to optimize their coding capacity. although growing evidence indicates the occurrence of ribosomal readthrough also in higher organisms, a biological function for the resulting extended proteins has been elucidated only in very few cases. here, we report that in human cells programmed stop codon readthrough is used to generate peroxisom ... | 2014 | 25340584 |
| autophagy restricts hiv-1 infection by selectively degrading tat in cd4+ t lymphocytes. | autophagy is a ubiquitous mechanism involved in the lysosomal-mediated degradation of cellular components when they are engulfed in vacuoles called autophagosomes. autophagy is also recognized as an important regulator of the innate and adaptive immune responses against numerous pathogens, which have, therefore, developed strategies to block or use the autophagy machinery to their own benefit. upon human immunodeficiency virus type 1 (hiv-1) infection, viral envelope (env) glycoproteins induce a ... | 2014 | 25339774 |
| the ubiquitin c-terminal hydrolase l1 (uch-l1) c terminus plays a key role in protein stability, but its farnesylation is not required for membrane association in primary neurons. | ubiquitin c-terminal hydrolase l1 (uch-l1) is a deubiquitinating enzyme that is highly expressed in neurons. a possible role for uch-l1 in neurodegeneration has been highlighted because of its presence in lewy bodies associated with parkinson disease and neurofibrillary tangles observed in alzheimer disease. uch-l1 exists in two forms in neurons, a soluble cytoplasmic form (uch-l1(c)) and a membrane-associated form (uch-l1(m)). alzheimer brains show reduced levels of soluble uch-l1(c) correlatin ... | 2014 | 25326379 |
| venezuelan equine encephalitis virus variants lacking transcription inhibitory functions demonstrate highly attenuated phenotype. | alphaviruses represent a significant public health threat worldwide. they are transmitted by mosquitoes and cause a variety of human diseases ranging from severe meningoencephalitis to polyarthritis. to date, no efficient and safe vaccines have been developed against any alphavirus infection. however, in recent years, significant progress has been made in understanding the mechanism of alphavirus replication and virus-host interactions. these data have provided the possibility for the developmen ... | 2014 | 25320296 |
| differentiation of neurons restricts arbovirus replication and increases expression of the alpha isoform of irf-7. | susceptibility to alphavirus infection is age dependent, and host maturation is associated with decreased virus replication and less severe encephalitis. to identify factors associated with maturation-dependent restriction of virus replication, we studied ap-7 rat olfactory bulb neuronal cells, which can differentiate in vitro. differentiation was associated with a 150- to 1,000-fold decrease in replication of the alphaviruses sindbis virus and venezuelan equine encephalitis virus, as well as la ... | 2014 | 25320290 |
| variations in ph sensitivity, acid stability, and fusogenicity of three influenza virus h3 subtypes. | influenza a virus strains adapt to achieve successful entry into host species. entry is mediated by the viral membrane protein hemagglutinin (ha), which triggers membrane fusion and genome release under acidic conditions in the endosome. in addition to changes in the receptor binding domain, the acid stability of ha has been linked to the successful transmission of virus between avian and human hosts. however, to fully understand the connection between changes in ha and host tropism, additional ... | 2014 | 25320308 |
| novel mode of isg15-mediated protection against influenza a virus and sendai virus in mice. | isg15 is a diubiquitin-like modifier and one of the most rapidly induced genes upon type i interferon stimulation. hundreds of host proteins and a number of viral proteins have been shown to be isgylated, and understanding how these modifications affect the interferon response and virus replication has been of considerable interest. isg15(-/-) mice exhibit increased susceptibility to viral infection, and in the case of influenza b virus and vaccinia virus, isg15 conjugation has been shown to res ... | 2014 | 25320315 |
| alginate hydrogel protects encapsulated hepatic huh-7 cells against hepatitis c virus and other viral infections. | cell microencapsulation in alginate hydrogel has shown interesting applications in regenerative medicine and the biomedical field through implantation of encapsulated tissue or for bioartificial organ development. although alginate solution is known to have low antiviral activity, the same property regarding alginate gel has not yet been studied. the aim of this work is to investigate the potential protective effect of alginate encapsulation against hepatitis c virus (hcv) infection for a hepati ... | 2014 | 25310111 |
| age-dependent myeloid dendritic cell responses mediate resistance to la crosse virus-induced neurological disease. | la crosse virus (lacv) is the major cause of pediatric viral encephalitis in the united states; however, the mechanisms responsible for age-related susceptibility in the pediatric population are not well understood. our current studies in a mouse model of lacv infection indicated that differences in myeloid dendritic cell (mdc) responses between weanling and adult mice accounted for susceptibility to lacv-induced neurological disease. we found that type i interferon (ifn) responses were signific ... | 2014 | 25008929 |
| short self-interacting n-terminal region of rubella virus capsid protein is essential for cooperative actions of capsid and nonstructural p150 proteins. | nucleocapsid formation is a primary function of the rubella virus capsid protein, which also promotes viral rna synthesis via an unknown mechanism. the present study demonstrates that in infected cells, the capsid protein is associated with the nonstructural p150 protein via the short self-interacting n-terminal region of the capsid protein. mutational analyses indicated that hydrophobic amino acids in this n-terminal region are essential for its n-terminal self-interaction, which is critical fo ... | 2014 | 25056903 |
| regulation of autophagic activation by rta of epstein-barr virus via the extracellular signal-regulated kinase pathway. | autophagy is an intracellular degradation pathway that provides a host defense mechanism against intracellular pathogens. however, many viruses exploit this mechanism to promote their replication. this study shows that lytic induction of epstein-barr virus (ebv) increases the membrane-bound form of lc3 (lc3-ii) and lc3-containing punctate structures in ebv-positive cells. transfecting 293t cells with a plasmid that expresses rta also induces autophagy, revealing that rta is responsible for autop ... | 2014 | 25122800 |
| a chimeric virus-mouse model system for evaluating the function and inhibition of papain-like proteases of emerging coronaviruses. | to combat emerging coronaviruses, developing safe and efficient platforms to evaluate viral protease activities and the efficacy of protease inhibitors is a high priority. here, we exploit a biosafety level 2 (bsl-2) chimeric sindbis virus system to evaluate protease activities and the efficacy of inhibitors directed against the papain-like protease (plpro) of severe acute respiratory syndrome coronavirus (sars-cov), a biosafety level 3 (bsl-3) pathogen. we engineered sindbis virus to coexpress ... | 2014 | 25100850 |
| engineering recombinant orsay virus directly in the metazoan host caenorhabditis elegans. | the recent identification of orsay virus, the first virus that is capable of naturally infecting caenorhabditis elegans, provides a unique opportunity to explore host-virus interaction studies in this invaluable model organism. a key feature of this system is the robust genetic tractability of the host, c. elegans, which would ideally be complemented by the ability to genetically manipulate orsay virus in parallel. to this end, we developed a plasmid-based reverse genetics system for orsay virus ... | 2014 | 25078701 |
| phosphatidylserine receptors: enhancers of enveloped virus entry and infection. | a variety of both rna and dna viruses envelop their capsids in a lipid bilayer. one of the more recently appreciated benefits this envelope is incorporation of phosphatidylserine (ptdser). surface exposure of ptdser disguises viruses as apoptotic bodies; tricking cells into engulfing virions. this mechanism is termed apoptotic mimicry. several ptdser receptors have been identified to enhance virus entry and we have termed this group of proteins ptdser-mediated virus entry enhancing receptors or ... | 2014 | 25277499 |
| potent immune responses in rhesus macaques induced by nonviral delivery of a self-amplifying rna vaccine expressing hiv type 1 envelope with a cationic nanoemulsion. | self-amplifying messenger rna (mrna) of positive-strand rna viruses are effective vectors for in situ expression of vaccine antigens and have potential as a new vaccine technology platform well suited for global health applications. the sam vaccine platform is based on a synthetic, self-amplifying mrna delivered by a nonviral delivery system. the safety and immunogenicity of an hiv sam vaccine encoding a clade c envelope glycoprotein formulated with a cationic nanoemulsion (cne) delivery system ... | 2014 | 25234719 |
| sponging of cellular proteins by viral rnas. | viral rnas accumulate to high levels during infection and interact with a variety of cellular factors including mirnas and rna-binding proteins. although many of these interactions exist to directly modulate replication, translation and decay of viral transcripts, evidence is emerging that abundant viral rnas may in certain cases serve as a sponge to sequester host non-coding rnas and proteins. by effectively reducing the ability of cellular rna binding proteins to regulate host cell gene expres ... | 2014 | 25233339 |
| virus-mediated compartmentalization of the host translational machinery. | viruses require the host translational apparatus to synthesize viral proteins. host stress response mechanisms that suppress translation, therefore, represent a significant obstacle that viruses must overcome. here, we report a strategy whereby the mammalian orthoreoviruses compartmentalize the translational machinery within virus-induced inclusions known as viral factories (vf). vf are the sites of reovirus replication and assembly but were thought not to contain ribosomes. it was assumed viral ... | 2014 | 25227463 |