| heterogeneous nuclear ribonucleoprotein k supports vesicular stomatitis virus replication by regulating cell survival and cellular gene expression. | the heterogeneous nuclear ribonucleoprotein k (hnrnp k) is a member of the family of hnrnps and was recently shown in a genome-wide small interfering rna (sirna) screen to support vesicular stomatitis virus (vsv) growth. to decipher the role of hnrnp k in vsv infection, we conducted studies which suggest that the protein is required for vsv spreading. virus binding to cells, entry, and nucleocapsid uncoating steps were not adversely affected in the absence of hnrnp k, whereas viral genome transc ... | 2013 | 23843646 |
| zebrafish isg15 exerts a strong antiviral activity against rna and dna viruses and regulates the interferon response. | isg15, a 15-kda interferon-induced protein that participates in antiviral defenses of mammals, is highly conserved among vertebrates. in fish, as in mammals, viral infection and interferon treatment induce isg15 expression. the two ubiquitin-like domains of isg15 and the presence of a consensus lrlrgg sequence in the c-terminal region, which is required for the covalent conjugation to a substrate protein, are also conserved in fish. our data demonstrate that overexpression of zebrafish isg15 (zf ... | 2013 | 23824820 |
| functional specialization of the small interfering rna pathway in response to virus infection. | in drosophila, post-transcriptional gene silencing occurs when exogenous or endogenous double stranded rna (dsrna) is processed into small interfering rnas (sirnas) by dicer-2 (dcr-2) in association with a dsrna-binding protein (dsrbp) cofactor called loquacious (loqs-pd). sirnas are then loaded onto argonaute-2 (ago2) by the action of dcr-2 with another dsrbp cofactor called r2d2. loaded ago2 executes the destruction of target rnas that have sequence complementarity to sirnas. although dcr-2, r ... | 2013 | 24009507 |
| non-encapsidation activities of the capsid proteins of positive-strand rna viruses. | viral capsid proteins (cps) are characterized by their role in forming protective shells around viral genomes. however, cps have additional and important roles in the virus infection cycles and in the cellular responses to infection. these activities involve cp binding to rnas in both sequence-specific and nonspecific manners as well as association with other proteins. this review focuses on cps of both plant and animal-infecting viruses with positive-strand rna genomes. we summarize the structu ... | 2013 | 24074574 |
| erk signaling couples nutrient status to antiviral defense in the insect gut. | a unique facet of arthropod-borne virus (arbovirus) infection is that the pathogens are orally acquired by an insect vector during the taking of a blood meal, which directly links nutrient acquisition and pathogen challenge. we show that the nutrient responsive erk pathway is both induced by and restricts disparate arboviruses in drosophila intestines, providing insight into the molecular determinants of the antiviral "midgut barrier." wild-type flies are refractory to oral infection by arboviru ... | 2013 | 23980175 |
| enhanced delivery and potency of self-amplifying mrna vaccines by electroporation in situ. | nucleic acid-based vaccines such as viral vectors, plasmid dna (pdna), and mrna are being developed as a means to address limitations of both live-attenuated and subunit vaccines. dna vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. electroporation delivery technologies have been shown to improve the generation of t and b cell responses from synthetic dna vaccines in many animal species an ... | 2013 | 26344119 |
| replication vesicles are load- and choke-points in the hepatitis c virus lifecycle. | hepatitis c virus (hcv) infection develops into chronicity in 80% of all patients, characterized by persistent low-level replication. to understand how the virus establishes its tightly controlled intracellular rna replication cycle, we developed the first detailed mathematical model of the initial dynamic phase of the intracellular hcv rna replication. we therefore quantitatively measured viral rna and protein translation upon synchronous delivery of viral genomes to host cells, and thoroughly ... | 2013 | 23990783 |
| detection of dengue viruses using reverse transcription-loop-mediated isothermal amplification. | early and rapid detection of dengue virus (denv) infection during the febrile period is crucial for proper patient management and prevention of disease spread. an easy to perform and highly sensitive method is needed for routine implementation especially in the resource-limited rural healthcare settings where dengue is endemic. | 2013 | 23964963 |
| coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence for proofreading and potential therapeutics. | no therapeutics or vaccines currently exist for human coronaviruses (hcovs). the severe acute respiratory syndrome-associated coronavirus (sars-cov) epidemic in 2002-2003, and the recent emergence of middle east respiratory syndrome coronavirus (mers-cov) in april 2012, emphasize the high probability of future zoonotic hcov emergence causing severe and lethal human disease. additionally, the resistance of sars-cov to ribavirin (rbv) demonstrates the need to define new targets for inhibition of c ... | 2013 | 23966862 |
| isolation of midgut escape mutants of two american genotype dengue 2 viruses from aedes aegypti. | several studies have shown that american genotype dengue 2 viruses (denv2) have reduced viral fitness in the mosquito vector, aedes aegypti, compared to other denv2 genotypes. diminished replication efficiency or inability to efficiently traverse membrane barriers encompassing organs such as the midgut or salivary glands are considered major factors negatively impacting viral fitness in the mosquito. | 2013 | 23937713 |
| amalgamating oncolytic viruses to enhance their safety, consolidate their killing mechanisms, and accelerate their spread. | oncolytic viruses are structurally and biologically diverse, spreading through tumors and killing them by various mechanisms and with different kinetics. here, we created a hybrid vesicular stomatitis/measles virus (vsv/mv) that harnesses the safety of oncolytic mv, the speed of vsv, and the tumor killing mechanisms of both viruses. oncolytic mv targets cd46 and kills by forcing infected cells to fuse with uninfected neighbors, but propagates slowly. vsv spreads rapidly, directly lysing tumor ce ... | 2013 | 23842448 |
| a prolyl-isomerase mediates dopamine-dependent plasticity and cocaine motor sensitization. | synaptic plasticity induced by cocaine and other drugs underlies addiction. here we elucidate molecular events at synapses that cause this plasticity and the resulting behavioral response to cocaine in mice. in response to d1-dopamine-receptor signaling that is induced by drug administration, the glutamate-receptor protein metabotropic glutamate receptor 5 (mglur5) is phosphorylated by microtubule-associated protein kinase (mapk), which we show potentiates pin1-mediated prolyl-isomerization of m ... | 0 | 23911326 |
| in vivo bioluminescent imaging of influenza a virus infection and characterization of novel cross-protective monoclonal antibodies. | influenza a virus is a major human pathogen responsible for seasonal epidemics as well as pandemic outbreaks. due to the continuing burden on human health, the need for new tools to study influenza virus pathogenesis as well as to evaluate new therapeutics is paramount. we report the development of a stable, replication-competent luciferase reporter influenza a virus that can be used for in vivo imaging of viral replication. this imaging is noninvasive and allows for the longitudinal monitoring ... | 2013 | 23698304 |
| natural variation in the heparan sulfate binding domain of the eastern equine encephalitis virus e2 glycoprotein alters interactions with cell surfaces and virulence in mice. | recently, we compared amino acid sequences of the e2 glycoprotein of natural north american eastern equine encephalitis virus (na-eeev) isolates and demonstrated that naturally circulating viruses interact with heparan sulfate (hs) and that this interaction contributes to the extreme neurovirulence of eeev (c. l. gardner, g. d. ebel, k. d. ryman, and w. b. klimstra, proc. natl. acad. sci. u. s. a., 108:16026-16031, 2011). in the current study, we have examined the contribution to hs binding of e ... | 2013 | 23720725 |
| activity increase in respiratory chain complexes by rubella virus with marginal induction of oxidative stress. | mitochondria are important for the viral life cycle, mainly by providing the energy required for viral replication and assembly. a highly complex interaction with mitochondria is exerted by rubella virus (rv), which includes an increase in the mitochondrial membrane potential as a general marker for mitochondrial activity. we aimed in this study to provide a more comprehensive picture of the activity of mitochondrial respiratory chain complexes i to iv. their activities were compared among three ... | 2013 | 23720730 |
| possible role of a cell surface carbohydrate in evolution of resistance to viral infections in old world primates. | due to inactivation of the α1,3-galactosyltransferase gene (ggta1, or the α1,3gt gene) approximately 28 million years ago, the carbohydrate αgal (galα1,3galβ1,4glcnac) is not expressed on the cells of old world monkeys and apes (including humans) but is expressed in all other mammals. the proposed selective advantage of this mutation for these primates is the ability to produce anti-gal antibodies, which may be an effective immune component in neutralizing αgal-expressing pathogens. however, los ... | 2013 | 23740988 |
| fusion of mapple and venus fluorescent proteins to the sindbis virus e2 protein leads to different cell-binding properties. | fluorescent proteins (fps) are widely used in real-time single virus particle studies to visualize, track and quantify the spatial and temporal parameters of viral pathways. however, potential functional differences between the wild type and the fp-tagged virus may specifically affect particular stages in the virus life-cycle. in this work, we genetically modified the e2 spike protein of sindbis virus (sinv) with two fps. we inserted mapple, a red fp, or venus, a yellow fp, at the n-terminus of ... | 2013 | 23916968 |
| inhibition of hiv-1 replication by secondary metabolites from endophytic fungi of desert plants. | most antiretroviral drugs currently in use to treat an hiv-1 infection are chemically synthesized and lead to the development of viral resistance, as well as cause severe toxicities. however, a largely unexplored source for hiv-1 drug discovery is endophytic fungi that live in a symbiotic relationship with plants. these fungi produce biologically active secondary metabolites, which are natural products that are beneficial to the host. we prepared several hundred extracts from endophytic fungi of ... | 2013 | 23961302 |
| metabolism of amyloid β peptide and pathogenesis of alzheimer's disease. | the conversion of what has been interpreted as "normal brain aging" to alzheimer's disease (ad) via transition states, i.e., preclinical ad and mild cognitive impairment, appears to be a continuous process caused primarily by aging-dependent accumulation of amyloid β peptide (aβ) in the brain. this notion however gives us a hope that, by manipulating the aβ levels in the brain, we may be able not only to prevent and cure the disease but also to partially control some very significant aspects of ... | 0 | 23883611 |
| optogenetic inhibition of synaptic release with chromophore-assisted light inactivation (cali). | optogenetic techniques provide effective ways of manipulating the functions of selected neurons with light. in the current study, we engineered an optogenetic technique that directly inhibits neurotransmitter release. we used a genetically encoded singlet oxygen generator, minisog, to conduct chromophore assisted light inactivation (cali) of synaptic proteins. fusions of minisog to vamp2 and synaptophysin enabled disruption of presynaptic vesicular release upon illumination with blue light. in c ... | 0 | 23889931 |
| the small gtpase arf1 modulates arp2/3-mediated actin polymerization via pick1 to regulate synaptic plasticity. | inhibition of arp2/3-mediated actin polymerization by pick1 is a central mechanism to ampa receptor (ampar) internalization and long-term depression (ltd), although the signaling pathways that modulate this process in response to nmda receptor (nmdar) activation are unknown. here, we define a function for the gtpase arf1 in this process. we show that arf1-gtp binds pick1 to limit pick1-mediated inhibition of arp2/3 activity. expression of mutant arf1 that does not bind pick1 leads to reduced sur ... | 0 | 23889934 |
| map1b-dependent rac activation is required for ampa receptor endocytosis during long-term depression. | the microtubule-associated protein 1b (map1b) plays critical roles in neurite growth and synapse maturation during brain development. this protein is well expressed in the adult brain. however, its function in mature neurons remains unknown. we have used a genetically modified mouse model and shrna techniques to assess the role of map1b at established synapses, bypassing map1b functions during neuronal development. under these conditions, we found that map1b deficiency alters synaptic plasticity ... | 2013 | 23881099 |
| viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways. | early innate and cell-intrinsic responses are essential to protect host cells against pathogens. in turn, viruses have developed sophisticated mechanisms to establish productive infections by counteracting host innate immune responses. increasing evidence indicates that these antiviral factors may have a dual role by directly inhibiting viral replication as well as by sensing and transmitting signals to induce antiviral cytokines. recent studies have pointed at new, unappreciated mechanisms of v ... | 2013 | 23850008 |
| active vaccination with vaccinia virus a33 protects mice against lethal vaccinia and ectromelia viruses but not against cowpoxvirus; elucidation of the specific adaptive immune response. | vaccinia virus protein a33 (a33vacv) plays an important role in protection against orthopoxviruses, and hence is included in experimental multi-subunit smallpox vaccines. in this study we show that single-dose vaccination with recombinant sindbis virus expressing a33vacv, is sufficient to protect mice against lethal challenge with vaccinia virus wr (vacv-wr) and ectromelia virus (ectv) but not against cowpox virus (cpxv), a closely related orthopoxvirus. moreover, a subunit vaccine based on the ... | 2013 | 23842430 |
| monitoring neuronal excitability at the synapse. | mammalian target of rapamycin (mtor) is a key player at the synapse regulating local translation and long-lasting synaptic plasticity. now, a new study by sosanya et al. (2013. j. cell biol. http://dx.doi.org/10.1083/jcb.201212089) investigates the molecular mechanism of how mtor suppresses local protein synthesis of a key potassium channel at activated synapses. | 0 | 23836926 |
| degradation of high affinity hud targets releases kv1.1 mrna from mir-129 repression by mtorc1. | little is known about how a neuron undergoes site-specific changes in intrinsic excitability during neuronal activity. we provide evidence for a novel mechanism for mtorc1 kinase-dependent translational regulation of the voltage-gated potassium channel kv1.1 messenger rna (mrna). we identified a microrna, mir-129, that repressed kv1.1 mrna translation when mtorc1 was active. when mtorc1 was inactive, we found that the rna-binding protein, hud, bound to kv1.1 mrna and promoted its translation. un ... | 0 | 23836929 |
| viral vectors for vaccine applications. | traditional approach of inactivated or live-attenuated vaccine immunization has resulted in impressive success in the reduction and control of infectious disease outbreaks. however, many pathogens remain less amenable to deal with the traditional vaccine strategies, and more appropriate vaccine strategy is in need. recent discoveries that led to increased understanding of viral molecular biology and genetics has rendered the used of viruses as vaccine platforms and as potential anti-cancer agent ... | 2013 | 23858400 |
| a genome-wide rnai screen reveals that mrna decapping restricts bunyaviral replication by limiting the pools of dcp2-accessible targets for cap-snatching. | bunyaviruses are an emerging group of medically important viruses, many of which are transmitted from insects to mammals. to identify host factors that impact infection, we performed a genome-wide rnai screen in drosophila and identified 131 genes that impacted infection of the mosquito-transmitted bunyavirus rift valley fever virus (rvfv). dcp2, the catalytic component of the mrna decapping machinery, and two decapping activators, ddx6 and lsm7, were antiviral against disparate bunyaviruses in ... | 0 | 23824541 |
| lipidome analysis of rotavirus-infected cells confirms the close interaction of lipid droplets with viroplasms. | rotaviruses (rvs) cause acute gastroenteritis in infants and young children, and are globally distributed. within the infected host cell, rvs establish replication complexes in viroplasms ('viral factories') to which lipid droplet organelles are recruited. to further understand this recently discovered phenomenon, the lipidomes of rv-infected and uninfected ma104 cells were investigated. cell lysates were subjected to equilibrium ultracentrifugation through iodixanol gradients. fourteen differen ... | 2013 | 23515026 |
| visualization of dc-sign-mediated entry pathway of engineered lentiviral vectors in target cells. | dendritic cells (dcs) are potent antigen-presenting cells and therefore have enormous potential as vaccine targets. we have previously developed an engineered lentiviral vector (lv) that is pseudotyped with a mutated sindbis virus glycoprotein (svgmu), which is capable of targeting dcs through dendritic cell-specific icam3-grabbing nonintegrin (dc-sign), a receptor that is predominantly expressed by dcs. in this study, we aimed to elucidate the internalization and trafficking mechanisms of this ... | 2013 | 23840690 |
| induction of apoptosis in mcf-7 cells by the hemagglutinin-neuraminidase glycoprotein of newcastle disease virus malaysian strain af2240. | newcastle disease virus (ndv) exerts its naturally occurring oncolysis possibly through the induction of apoptosis. we hypothesized that the binding of the virus to the cell via the hemagglutinin-neuraminidase (hn) glycoprotein may be sufficient to not only induce apoptosis but to induce a higher apoptosis level than the parental ndv af2240 virus. ndv af2240 induction of apoptosis in mcf-7 human breast cancer cells was analyzed and quantified. in addition, the complete hn gene of ndv strain af22 ... | 2013 | 23807159 |
| mature neurons: equipped for survival. | neurons completely transform how they regulate cell death over the course of their lifetimes. developing neurons freely activate cell death pathways to fine-tune the number of neurons that are needed during the precise formation of neural networks. however, the regulatory balance between life and death shifts as neurons mature beyond early development. mature neurons promote survival at all costs by employing multiple, often redundant, strategies to prevent cell death by apoptosis. this dramatic ... | 2013 | 23807218 |
| understanding and altering cell tropism of vesicular stomatitis virus. | vesicular stomatitis virus (vsv) is a prototypic nonsegmented negative-strand rna virus. vsv's broad cell tropism makes it a popular model virus for many basic research applications. in addition, a lack of preexisting human immunity against vsv, inherent oncotropism and other features make vsv a widely used platform for vaccine and oncolytic vectors. however, vsv's neurotropism that can result in viral encephalitis in experimental animals needs to be addressed for the use of the virus as a safe ... | 2013 | 23796410 |
| a short hairpin rna screen of interferon-stimulated genes identifies a novel negative regulator of the cellular antiviral response. | the type i interferon (ifn) signaling pathway restricts infection of many divergent families of rna and dna viruses by inducing hundreds of ifn-stimulated genes (isgs), some of which have direct antiviral activity. we screened 813 short hairpin rna (shrna) constructs targeting 245 human isgs using a flow cytometry approach to identify genes that modulated infection of west nile virus (wnv) in ifn-β-treated human cells. thirty isgs with inhibitory effects against wnv were identified, including se ... | 2013 | 23781071 |
| prenylome profiling reveals s-farnesylation is crucial for membrane targeting and antiviral activity of zap long-isoform. | s-prenylation is an important lipid modification that targets proteins to membranes for cell signaling and vesicle trafficking in eukaryotes. as s-prenylated proteins are often key effectors for oncogenesis, congenital disorders, and microbial pathogenesis, robust proteomic methods are still needed to biochemically characterize these lipidated proteins in specific cell types and disease states. here, we report that bioorthogonal proteomics of macrophages with an improved alkyne-isoprenoid chemic ... | 2013 | 23776219 |
| neuro-invasion of chandipura virus mediates pathogenesis in experimentally infected mice. | neuro-tropism is a major feature in many viral infections. chandipura virus produces neurological symptoms in naturally infected young children and experimentally infected suckling mice. this study was undertaken to find out the neuro-invasive behaviour of chandipura virus in suckling mice. the suckling mice were infected with the virus via footpad injection. different tissues were collected at 24-h intervals up to 96-h post infection and processed for virus quantification and histological study ... | 2013 | 23826408 |
| recombinant varicella-zoster virus vaccines as platforms for expression of foreign antigens. | varicella-zoster virus (vzv) vaccines induce immunity against childhood chickenpox and against shingles in older adults. the safety, efficacy, and widespread use of vzv vaccines suggest that they may also be effective as recombinant vaccines against other infectious diseases that affect the young and the elderly. the generation of recombinant vzv vaccines and their evaluation in animal models are reviewed. the potential advantages and limitations of recombinant vzv vaccines are addressed. | 2013 | 23843791 |
| cytoplasmic rna viruses as potential vehicles for the delivery of therapeutic small rnas. | viral vectors have become the best option for the delivery of therapeutic genes in conventional and rna interference-based gene therapies. the current viral vectors for the delivery of small regulatory rnas are based on dna viruses and retroviruses/lentiviruses. cytoplasmic rna viruses have been excluded as viral vectors for rnai therapy because of the nuclear localization of the microprocessor complex and the potential degradation of the viral rna genome during the excision of any virus-encoded ... | 2013 | 23759022 |
| inhibition of human immunodeficiency virus type-1 through autophagy. | as an obligatory intracellular pathogen, human immunodeficiency virus type-1 (hiv) is dependent upon its ability to exploit host cell machinery for replication and dissemination, and to circumvent cellular processes that prevent its growth. one such intracellular process is autophagy, a component of the host defense against hiv with roles in innate immune signaling, adaptive immunity and intracellular degradation of hiv. during permissive infection, hiv down-modulates autophagy, promoting its ow ... | 2013 | 23747172 |
| the relationship between metabolism and the autophagy machinery during the innate immune response. | the innate immune response is shaped by multiple factors, including both traditional autophagy and lc3-associated phagocytosis (lap). as the autophagic machinery is engaged during times of nutrient stress, arising from scarcity or pathogens, we examine how autophagy, specifically lap, and cellular metabolism together influence macrophage function and the innate immune response. | 0 | 23747248 |
| chikungunya virus host range e2 transmembrane deletion mutants induce protective immunity against challenge in c57bl/6j mice. | a vaccine against chikungunya virus (chikv), a reemerging pathogenic arbovirus, has been made by attenuating wild-type (wt) virus via truncation of the transmembrane domain (tmd) of e2 and selecting for host range (hr) mutants. mice are a standard model system for chikv disease and display the same symptoms of the disease seen in humans. groups of mice were inoculated with one of three chikv hr mutants to determine the ability of each mutant strain to elicit neutralizing antibody and protective ... | 2013 | 23552427 |
| the receptor attachment function of measles virus hemagglutinin can be replaced with an autonomous protein that binds her2/neu while maintaining its fusion-helper function. | cell entry of enveloped viruses is initiated by attachment to the virus receptor followed by fusion between the virus and host cell membranes. measles virus (mv) attachment to its receptor is mediated by the hemagglutinin (h), which is thought to produce conformational changes in the membrane fusion protein (f) that trigger insertion of its fusion peptide into the target cell membrane. here, we uncoupled receptor attachment and the fusion-helper function of h by introducing y481a, r533a, s548l, ... | 2013 | 23536664 |
| mda5 localizes to stress granules, but this localization is not required for the induction of type i interferon. | virus infection can initiate a type i interferon (ifn-α/β) response via activation of the cytosolic rna sensors retinoic acid-inducible gene-i (rig-i) and melanoma differentiation-associated gene 5 (mda5). furthermore, it can activate kinases that phosphorylate eukaryotic translation initiation factor 2α (eif2α), which leads to inhibition of (viral) protein translation and formation of stress granules (sg). most viruses have evolved mechanisms to suppress these cellular responses. here, we show ... | 2013 | 23536668 |
| oncolytic virotherapy: the questions and the promise. | oncolytic virotherapy is a new strategy to reduce tumor burden through selective virus replication in rapidly proliferating cells. oncolytic viruses are members of at least ten virus families, each with its advantages and disadvantages. here, i briefly review the recent advances and key challenges, as exemplified by the best-studied platforms. recent advances include preclinical proof of feasibility, clinical evidence of tolerability and effectiveness, and the development of new strategies to im ... | 2013 | 27512655 |
| inducible interleukin 32 (il-32) exerts extensive antiviral function via selective stimulation of interferon λ1 (ifn-λ1). | interleukin (il)-32 has been recognized as a proinflammatory cytokine that participates in responses to viral infection. however, little is known about how il-32 is induced in response to viral infection and the mechanisms of il-32-mediated antiviral activities. we discovered that il-32 is elevated by hepatitis b virus (hbv) infection both in vitro and in vivo and that hbv induced il-32 expression at the level of both transcription and post-transcription. furthermore, microrna-29b was found to b ... | 2013 | 23729669 |
| hepatitis e: molecular virology and pathogenesis. | hepatitis e virus is a single, positive-sense, capped and poly a tailed rna virus classified under the family hepeviridae. enteric transmission, acute self-limiting hepatitis, frequent epidemic and sporadic occurrence, high mortality in affected pregnants are hallmarks of hepatitis e infection. lack of an efficient culture system and resulting reductionist approaches for the study of replication and pathogenesis of hev made it to be a less understood agent. early studies on animal models, sub-ge ... | 2013 | 25755485 |
| iron absorption in drosophila melanogaster. | the way in which drosophila melanogaster acquires iron from the diet remains poorly understood despite iron absorption being of vital significance for larval growth. to describe the process of organismal iron absorption, consideration needs to be given to cellular iron import, storage, export and how intestinal epithelial cells sense and respond to iron availability. here we review studies on the divalent metal transporter-1 homolog malvolio (iron import), the recent discovery that multicopper o ... | 2013 | 23686013 |
| architecture and biogenesis of plus-strand rna virus replication factories. | plus-strand rna virus replication occurs in tight association with cytoplasmic host cell membranes. both, viral and cellular factors cooperatively generate distinct organelle-like structures, designated viral replication factories. this compartmentalization allows coordination of the different steps of the viral replication cycle, highly efficient genome replication and protection of the viral rna from cellular defense mechanisms. electron tomography studies conducted during the last couple of y ... | 0 | 24175228 |
| macroautophagy--friend or foe of viral replication? | | 2013 | 23661081 |
| mosquito-borne arbovirus surveillance at selected sites in diverse ecological zones of kenya; 2007 - 2012. | increased frequency of arbovirus outbreaks in east africa necessitated the determination of distribution of risk by entomologic arbovirus surveillance. a systematic vector surveillance programme spanning 5 years and covering 11 sites representing seven of the eight provinces in kenya and located in diverse ecological zones was carried out. | 2013 | 23663381 |
| antimicrobial autophagy: a conserved innate immune response in drosophila. | autophagy is a highly conserved degradative pathway that has rapidly emerged as a critical component of immunity and host defense. studies have implicated autophagy genes in restricting the replication of a diverse array of pathogens, including bacteria, viruses and protozoans. however, in most cases, the in vivo role of antimicrobial autophagy against pathogens has been undefined. drosophila provides a genetically tractable model system that can be easily adapted to study autophagy in innate im ... | 2013 | 23689401 |
| malaria infection does not affect the sensitivity of peripheral receptor neurons in anopheles stephensi. | mosquitoes transmit many important diseases including malaria, dengue and yellow fever. disease transmission from one vertebrate host to another depends on repeated blood feedings by single mosquitoes. in order for the mosquito to acquire the blood that it needs to complete oogenesis, the insect must locate a suitable host. olfactory cues (including carbon dioxide) released by the host and detected by the mosquito are the primary signals that vector insects use for host location. previous studie ... | 2013 | 23642231 |
| anti-hypertrophic and anti-oxidant effect of beta3-adrenergic stimulation in myocytes requires differential neuronal nos phosphorylation. | stimulation of β3-adrenoreceptors (β3-ar) blunts contractility and improves chronic left ventricular function in hypertrophied and failing hearts in a neuronal nitric oxide synthase (nnos) dependent manner. nnos can be regulated by post-translational modification of stimulatory phosphorylation residue ser1412 and inhibitory residue ser847. however, the role of phosphorylation of these residues in cardiomyocytes and β3-ar protective signaling has yet to be explored. | 2013 | 23643588 |
| fatal neurological respiratory insufficiency is common among viral encephalitides. | neurological respiratory insufficiency strongly correlates with mortality among rodents infected with west nile virus (wnv), which suggests that this is a primary mechanism of death in rodents and possibly fatal west nile neurological disease in human patients. | 2013 | 23641019 |
| rna-based mechanisms regulating host-virus interactions. | rna interference (rnai) is an ancient process by which non-coding rnas regulate gene expression in a sequence-specific manner. the core components of rnai are small regulatory rnas, approximately 21-30 nucleotides in length, including small interfering rnas (sirnas) and micrornas (mirnas). the past two decades have seen considerable progress in our understanding of the molecular mechanisms underlying the biogenesis of sirnas and mirnas. recent advances have also revealed the crucial regulatory r ... | 0 | 23550641 |
| norwalk virus minor capsid protein vp2 associates within the vp1 shell domain. | the major capsid protein of norovirus vp1 assembles to form an icosahedral viral particle. despite evidence that the norwalk virus (nv) minor structural protein vp2 is present in infectious virions, the available crystallographic and electron cryomicroscopy structures of nv have not revealed the location of vp2. in this study, we determined that vp1 associates with vp2 at the interior surface of the capsid, specifically with the shell (s) domain of vp1. we mapped the interaction site to amino ac ... | 2013 | 23408637 |
| hierarchy of orofacial rhythms revealed through whisking and breathing. | whisking and sniffing are predominant aspects of exploratory behaviour in rodents. yet the neural mechanisms that generate and coordinate these and other orofacial motor patterns remain largely uncharacterized. here we use anatomical, behavioural, electrophysiological and pharmacological tools to show that whisking and sniffing are coordinated by respiratory centres in the ventral medulla. we delineate a distinct region in the ventral medulla that provides rhythmic input to the facial motor neur ... | 2013 | 23624373 |
| postsynaptic kainate receptor recycling and surface expression are regulated by metabotropic autoreceptor signalling. | kainate receptors (kars) play fundamentally important roles in controlling synaptic function and regulating neuronal excitability. postsynaptic kars contribute to excitatory neurotransmission but the molecular mechanisms underlying their activity-dependent surface expression are not well understood. strong activation of kars in cultured hippocampal neurons leads to the downregulation of postsynaptic kars via endocytosis and degradation. in contrast, low-level activation augments postsynaptic kar ... | 2013 | 23556457 |
| a mobile genetic element with unknown function found in distantly related viruses. | the genetic element s2m seems to represent one of very few examples of mobile genetic elements in viruses. the function remains obscure and a scattered taxonomical distribution has been reported by numerous groups. | 2013 | 23618040 |
| nmda receptor subunit composition determines beta-amyloid-induced neurodegeneration and synaptic loss. | aggregates of amyloid-beta (aβ) and tau are hallmarks of alzheimer's disease (ad) leading to neurodegeneration and synaptic loss. while increasing evidence suggests that inhibition of n-methyl-d-aspartate receptors (nmdars) may mitigate certain aspects of ad neuropathology, the precise role of different nmdar subtypes for aβ- and tau-mediated toxicity remains to be elucidated. using mouse organotypic hippocampal slice cultures from arcaβ transgenic mice combined with sindbis virus-mediated expre ... | 2013 | 23618906 |
| the protective roles of autophagy in ischemic preconditioning. | autophagy, a process for the degradation of protein aggregates and dysfunctional organelles, is required for cellular homeostasis and cell survival in response to stress and is implicated in endogenous protection. ischemic preconditioning is a brief and nonlethal episode of ischemia, confers protection against subsequent ischemia-reperfusion through the up-regulation of endogenous protective mechanisms. emerging evidence shows that autophagy is associated with the protective effect of ischemic p ... | 2013 | 23603984 |
| membrane curvature in flaviviruses. | coordinated interplay between membrane proteins and the lipid bilayer is required for such processes as transporter function and the entrance of enveloped viruses into host cells. in this study, three-dimensional cryo-electron microscopy density maps of mature and immature flaviviruses were analyzed to assess the curvature of the membrane leaflets and its relation to membrane-bound viral glycoproteins. the overall morphology of the viral membrane is determined by the icosahedral scaffold compose ... | 2013 | 23602814 |
| viral precursor polyproteins: keys of regulation from replication to maturation. | many viruses use a replication strategy involving the translation of a large polyprotein, which is cleaved by viral and/or cellular proteases. several of these viruses severely impact human health around the globe, including hiv, hcv, dengue virus, and west nile virus. this method of genome organization has many benefits to the virus such as condensation of genetic material, as well as temporal and spatial regulation of protein activity depending on polyprotein cleavage state. the study of polyp ... | 2013 | 23602469 |
| do viruses require the cytoskeleton? | it is generally thought that viruses require the cytoskeleton during their replication cycle. however, recent experiments in our laboratory with rubella virus, a member of the family togaviridae (genus rubivirus), revealed that replication proceeded in the presence of drugs that inhibit microtubules. this study was done to expand on this observation. | 2013 | 23597412 |
| postexit surface engineering of retroviral/lentiviral vectors. | gene delivery vectors based on retroviral or lentiviral particles are considered powerful tools for biomedicine and biotechnology applications. such vectors require modification at the genomic level in the form of rearrangements to allow introduction of desired genes and regulatory elements (genotypic modification) as well as engineering of the physical virus particle (phenotypic modification) in order to mediate efficient and safe delivery of the genetic information to the target cell nucleus. ... | 2013 | 23691494 |
| virus infections in the nervous system. | virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (ns), spreading into the peripheral (pns) and more rarely the central (cns) nervous systems. the cns is protected from most virus infections by effective immune responses and multilayer barriers. however, some viruses enter the ns with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. ... | 0 | 23601101 |
| beclin 1 and nuclear factor-κbp65 are upregulated in hepatocellular carcinoma. | there are no sensitive and specific biomarkers that aid in the clinical diagnosis and prognosis of hepatocellular carcinoma (hcc). the aim of the present study was to determine the mrna and protein expression levels of beclin 1 (becn1) and nuclear factor-κb (nf-κb)p65 in patients with hcc, to evaluate their value as potential diagnostic and prognostic biomarkers. immunohistochemistry and in situ hybridization were used to detect the expression of hepatic becn1 and nf-kbp65 in patients with hcc, ... | 2013 | 23833647 |
| isg15: leading a double life as a secreted molecule. | isg15 is a well-known intracellular ubiquitin-like molecule involved in isgylation. however, a recent study has revived the notion first put forward two decades ago that isg15 is also a secreted molecule. human neutrophils, monocytes and lymphocytes can release isg15, even though this protein has no detectable signal peptide sequence. isg15 has also been found in the secretory granules of granulocytes. the mechanism underlying isg15 secretion is unknown. secreted isg15 acts on at least t and nat ... | 2013 | 23579383 |
| striatal neurones have a specific ability to respond to phasic dopamine release. | the camp/protein kinase a (pka) signalling cascade is ubiquitous, and each step in this cascade involves enzymes that are expressed in multiple isoforms. we investigated the effects of this diversity on the integration of the pathway in the target cell by comparing prefrontal cortical neurones with striatal neurones which express a very specific set of signalling proteins. the prefrontal cortex and striatum both receive dopaminergic inputs and we analysed the dynamics of the camp/pka signal trig ... | 2013 | 23551948 |
| regulation of stress granules and p-bodies during rna virus infection. | rna granules are structures within cells that play major roles in gene expression and homeostasis. two principle kinds of rna granules are conserved from yeast to mammals: stress granules (sgs), which contain stalled translation initiation complexes, and processing bodies (p-bodies, pbs), which are enriched with factors involved in rna turnover. since rna granules are associated with silenced transcripts, viruses subvert rna granule function for replicative advantages. this review, focusing on r ... | 2013 | 23554219 |
| tumor-specific targeting with modified sindbis viral vectors: evaluation with optical imaging and positron emission tomography in vivo. | sindbis virus (sinv) infect tumor cells specifically and systemically throughout the body. sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. the ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option. | 0 | 22847302 |
| transfer and expression of small interfering rnas in mammalian cells using lentiviral vectors. | rna interference is a convenient tool for modulating gene expression. the widespread application of rna interference is made difficult because of the imperfections of the methods used for efficient target cell delivery of whatever genes are under study. one of the most convenient and efficient gene transfer and expression systems is based on the use of lentiviral vectors, which direct the synthesis of small hairpin rnas (shrnas), the precursors of sirnas. the application of these systems enables ... | 0 | 23819033 |
| alphavirus genome delivery occurs directly at the plasma membrane in a time- and temperature-dependent process. | it is widely held that arboviruses such as the alphavirus sindbis virus gain entry into cells by a process of receptor-mediated endocytosis followed by membrane fusion in the acid environment of the endosome. we have used an approach of direct observation of sindbis virus entry into cells by electron microscopy and immunolabeling of virus proteins with antibodies conjugated to gold beads. we found that upon attaching to the cell surface, intact rna-containing viruses became empty shells that cou ... | 2013 | 23388718 |
| an antiviral role for antimicrobial peptides during the arthropod response to alphavirus replication. | alphaviruses establish a persistent infection in arthropod vectors which is essential for the effective transmission of the virus to vertebrate hosts. the development of persistence in insects is not well understood, although it is thought to involve the innate immune response. using a transgenic fly system expressing a self-replicating viral rna genome analog, we have previously demonstrated antiviral roles of the drosophila imd (immune deficiency) and jak-stat innate immunity pathways in respo ... | 2013 | 23365449 |
| an rna element in human interleukin 6 confers escape from degradation by the gammaherpesvirus sox protein. | several viruses express factors to silence host gene expression via widespread mrna degradation. this phenotype is the result of the coordinated activity of the viral endonuclease sox and the cellular rna degradation enzyme xrn1 during lytic kaposi's sarcoma-associated herpesvirus (kshv) infection. while most cellular transcripts are highly downregulated, a subset of host mrna escapes turnover via unknown mechanisms. one of the most prominent escapees is the interleukin 6 (il-6) mrna, which accu ... | 2013 | 23408619 |
| venezuelan equine encephalitis virus nsp2 protein regulates packaging of the viral genome into infectious virions. | alphaviruses are one of the most geographically widespread and yet often neglected group of human and animal pathogens. they are capable of replicating in a wide variety of cells of both vertebrate and insect origin and are widely used for the expression of heterologous genetic information both in vivo and in vitro. in spite of their use in a range of research applications and their recognition as a public health threat, the biology of alphaviruses is insufficiently understood. in this study, we ... | 2013 | 23365438 |
| 5-(perylen-3-yl)ethynyl-arabino-uridine (auy11), an arabino-based rigid amphipathic fusion inhibitor, targets virion envelope lipids to inhibit fusion of influenza virus, hepatitis c virus, and other enveloped viruses. | entry of enveloped viruses requires fusion of viral and cellular membranes. fusion requires the formation of an intermediate stalk structure, in which only the outer leaflets are fused. the stalk structure, in turn, requires the lipid bilayer of the envelope to bend into negative curvature. this process is inhibited by enrichment in the outer leaflet of lipids with larger polar headgroups, which favor positive curvature. accordingly, phospholipids with such shape inhibit viral fusion. we previou ... | 2013 | 23283943 |
| novel benzoxazole inhibitor of dengue virus replication that targets the ns3 helicase. | dengue virus (denv) is the predominant mosquito-borne viral pathogen that infects humans with an estimated 50 to 100 million infections per year worldwide. over the past 50 years, the incidence of dengue disease has increased dramatically and the virus is now endemic in more than 100 countries. moreover, multiple serotypes of denv are now found in the same geographic region, increasing the likelihood of more severe forms of disease. despite extensive research, there are still no approved vaccine ... | 2013 | 23403421 |
| a ubiquitin-specific protease possesses a decisive role for adenovirus replication and oncogene-mediated transformation. | adenoviral replication depends on viral as well as cellular proteins. however, little is known about cellular proteins promoting adenoviral replication. in our screens to identify such proteins, we discovered a cellular component of the ubiquitin proteasome pathway interacting with the central regulator of adenoviral replication. our binding assays mapped a specific interaction between the n-terminal domains of both viral e1b-55k and usp7, a deubiquitinating enzyme. rna interference-mediated dow ... | 2013 | 23555268 |
| molecular determinants of mouse neurovirulence and mosquito infection for western equine encephalitis virus. | western equine encephalitis virus (weev) is a naturally occurring recombinant virus derived from ancestral sindbis and eastern equine encephalitis viruses. we previously showed that infection by weev isolates mcmillan (mcm) and imp-181 (imp) results in high (∼90-100%) and low (0%) mortality, respectively, in outbred cd-1 mice when virus is delivered by either subcutaneous or aerosol routes. however, relatively little is known about specific virulence determinants of weev. we previously observed ... | 2013 | 23544138 |
| evolution of sindbis virus with a low-methionine-resistant phenotype is dependent both on a pre-existing mutation and on the methionine concentration in the medium. | svlm21 is a mutant of sindbis virus which was isolated by serial passage of virus in mosquito cells maintained in low-methionine medium; it therefore has a low-methionine-resistant (lmr) phenotype. this phenotype requires mutations at nts 319 and 321; these mutations result in arg to leu and ser to cys changes at positions 87 and 88 respectively in the viral methyl transferase, nsp1. to better understand the genesis of svlm21, we carried out serial passages of viruses having only one of these am ... | 2013 | 23544150 |
| baculovirus-mediated gene transfer in butterfly wings in vivo: an efficient expression system with an anti-gp64 antibody. | candidate genes for color pattern formation in butterfly wings have been known based on gene expression patterns since the 1990s, but their functions remain elusive due to a lack of a functional assay. several methods of transferring and expressing a foreign gene in butterfly wings have been reported, but they have suffered from low success rates or low expression levels. here, we developed a simple, practical method to efficiently deliver and express a foreign gene using baculovirus-mediated ge ... | 2013 | 23522444 |
| adaptation of enterovirus 71 to adult interferon deficient mice. | non-polio enteroviruses, including enterovirus 71 (ev71), have caused severe and fatal cases of hand, foot and mouth disease (hfmd) in the asia-pacific region. the development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. in this study, a mouse adapted ev71 strain was produced by conducting serial passages through a129 (α/β interferon (ifn) receptor deficient) and ag129 (α/β, γ ifn receptor deficient) mice. a b2 sub genotype of ... | 2013 | 23527208 |
| moving h5n1 studies into the era of systems biology. | the dynamics of h5n1 influenza virus pathogenesis are multifaceted and can be seen as an emergent property that cannot be comprehended without looking at the system as a whole. in past years, most of the high-throughput studies on h5n1-host interactions have focused on the host transcriptomic response, at the cellular or the lung tissue level. these studies pointed out that the dynamics and magnitude of the innate immune response and immune cell infiltration is critical to h5n1 pathogenesis. how ... | 2013 | 23499671 |
| intracellular antibody-bound pathogens stimulate immune signaling via the fc receptor trim21. | during pathogen infection, antibodies can be carried into the infected cell, where they are detected by the ubiquitously expressed cytosolic antibody receptor trim21. here we found that recognition of intracellular antibodies by trim21 activated immune signaling. trim21 catalyzed the formation of lys63 (k63)-linked ubiquitin chains and stimulated the transcription factor pathways of nf-κb, ap-1, irf3, irf5 and irf7. activation resulted in the production of proinflammatory cytokines, modulation o ... | 2013 | 23455675 |
| differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded rna viruses. | although susceptibility of neurons in the brain to microbial infection is a major determinant of clinical outcome, little is known about the molecular factors governing this vulnerability. here we show that two types of neurons from distinct brain regions showed differential permissivity to replication of several positive-stranded rna viruses. granule cell neurons of the cerebellum and cortical neurons from the cerebral cortex have unique innate immune programs that confer differential susceptib ... | 2013 | 23455712 |
| astrocyte-derived cxcl10 drives accumulation of antibody-secreting cells in the central nervous system during viral encephalomyelitis. | microbial infections of the central nervous system (cns) are often associated with local accumulation of antibody (ab)-secreting cells (asc). by providing a source of ab at the site of infection, cns-localized asc play a critical role in acute viral control and in preventing viral recrudescence. following coronavirus-induced encephalomyelitis, the cns accumulation of asc is chemokine (c-x-c motif) receptor 3 (cxcr3) dependent. this study demonstrates that cns-expressed cxcr3 ligand cxcl10 is the ... | 2013 | 23302888 |
| filoviruses utilize glycosaminoglycans for their attachment to target cells. | filoviruses are the cause of severe hemorrhagic fever in human and nonhuman primates. the envelope glycoprotein (gp), responsible for both receptor binding and fusion of the virus envelope with the host cell membrane, has been demonstrated to interact with multiple molecules in order to enhance entry into host cells. here we have demonstrated that filoviruses utilize glycosaminoglycans, and more specifically heparan sulfate proteoglycans, for their attachment to host cells. this interaction is m ... | 2013 | 23302881 |
| zap inhibits murine gammaherpesvirus 68 orf64 expression and is antagonized by rta. | zinc finger antiviral protein (zap) is an interferon-inducible host antiviral factor that specifically inhibits the replication of certain viruses, including hiv-1 and ebola virus. zap functions as a dimer formed through intermolecular interactions of its n-terminal tails. zap binds directly to specific viral mrnas and inhibits their expression by repressing translation and/or promoting degradation of the target mrna. zap is not a universal antiviral factor, since some viruses grow normally in z ... | 2012 | 23255809 |
| autophagy as an innate immune modulator. | autophagy is a fundamental cellular process in eukaryotic cells for maintaining homeostasis by degrading cellular proteins and organelles. recently, the roles of autophagy have been expanded to immune systems, which in turn modulate innate immune responses. more specifically, autophagy acts as a direct effector for protection against pathogens, as well as a modulator of pathogen recognition and downstream signaling in innate immune responses. in addition, autophagy controls autoimmunity and infl ... | 2013 | 23559894 |
| sustained activation of akt elicits mitochondrial dysfunction to block plasmodium falciparum infection in the mosquito host. | the overexpression of activated, myristoylated akt in the midgut of female transgenic anopheles stephensi results in resistance to infection with the human malaria parasite plasmodium falciparum but also decreased lifespan. in the present study, the understanding of mitochondria-dependent midgut homeostasis has been expanded to explain this apparent paradox in an insect of major medical importance. given that akt signaling is essential for cell growth and survival, we hypothesized that sustained ... | 2013 | 23468624 |
| acute bdnf treatment upregulates glur1-sap97 and glur2-grip1 interactions: implications for sustained ampa receptor expression. | brain-derived neurotrophic factor (bdnf) plays several prominent roles in synaptic plasticity and in learning and memory formation. reduced bdnf levels and altered bdnf signaling have been reported in several brain diseases and behavioral disorders, which also exhibit reduced levels of ampar subunits. bdnf treatment acutely regulates ampa receptor expression and function, including synaptic ampar subunit trafficking, and implicates several well defined signaling molecules that are required to el ... | 2013 | 23460828 |
| immune responses of a native and an invasive bird to buggy creek virus (togaviridae: alphavirus) and its arthropod vector, the swallow bug (oeciacus vicarius). | invasive species often display different patterns of parasite burden and virulence compared to their native counterparts. these differences may be the result of variability in host-parasite co-evolutionary relationships, the occurrence of novel host-parasite encounters, or possibly innate differences in physiological responses to infection between invasive and native hosts. here we examine the adaptive, humoral immune responses of a resistant, native bird and a susceptible, invasive bird to an a ... | 2013 | 23460922 |
| the δ2 glutamate receptor gates long-term depression by coordinating interactions between two ampa receptor phosphorylation sites. | long-term depression (ltd) commonly affects learning and memory in various brain regions. although cerebellar ltd absolutely requires the δ2 glutamate receptor (glud2) that is expressed in purkinje cells, ltd in other brain regions does not; why and how cerebellar ltd is regulated by glud2 remains unelucidated. here, we show that the activity-dependent phosphorylation of serine 880 (s880) in glua2 ampa receptor subunit, which is an essential step for ampa receptor endocytosis during ltd inductio ... | 2013 | 23431139 |
| metabotropic nmda receptor function is required for β-amyloid-induced synaptic depression. | the mechanisms by which β-amyloid (aβ), a peptide fragment believed to contribute to alzheimer's disease, leads to synaptic deficits are not known. here we find that elevated oligomeric aβ requires ion flux-independent function of nmda receptors (nmdars) to produce synaptic depression. aβ activates this metabotropic nmdar function on glun2b-containing nmdars but not on those containing glun2a. furthermore, oligomeric aβ leads to a selective loss of synaptic glun2b responses, effecting a switch i ... | 2013 | 23431156 |
| interferon-induced isg15 pathway: an ongoing virus-host battle. | isg15 is an interferon (ifn)-induced ubiquitin-like protein that is conjugated to target proteins via the sequential action of three enzymes that are also induced by ifn. unlike ubiquitin, which is highly conserved, the sequence of isg15 varies between species. isg15 conjugation inhibits many viruses, and free (unconjugated) isg15 can also act as an antiviral protein. in this review, we focus on the antiviral role of isg15 conjugation and on countermeasures employed by several viruses. the count ... | 2013 | 23414970 |
| development of one-step quantitative reverse transcription pcr for the rapid detection of flaviviruses. | the genus flavivirus includes several pathogenic agents that cause severe illness in humans. re-emergence of west nile virus in europe and continuous spread of certain flaviviruses such as dengue, yellow fever and japanese encephalitis viruses represent a global danger to public health. therefore, a rapid and accurate molecular method is required for diagnostics and epidemiological surveillance of flaviviruses. | 2013 | 23410000 |
| dugbe virus ovarian tumour domain interferes with ubiquitin/isg15-regulated innate immune cell signalling. | the ovarian tumour (otu) domain of the nairovirus l protein has been shown to remove ubiquitin and interferon-stimulated gene 15 protein (isg15) from host cell proteins, which is expected to have multiple effects on cell signalling pathways. we have confirmed that the otu domain from the l protein of the apathogenic nairovirus dugbe virus has deubiquitinating and deisgylating activity and shown that, when expressed in cells, it is highly effective at blocking the tnf-α/nf-κb and interferon/jak/s ... | 2012 | 23136361 |
| transgene-mediated suppression of the rna interference pathway in aedes aegypti interferes with gene silencing and enhances sindbis virus and dengue virus type 2 replication. | rna interference (rnai) is the major innate antiviral pathway in aedes aegypti that responds to replicating arboviruses such as dengue virus (denv) and sindbis virus (sinv). on the one hand, the mosquito's rnai machinery is capable of completely eliminating denv2 from ae. aegypti. on the other, transient silencing of key genes of the rnai pathway increases replication of sinv and denv2, allowing the viruses to temporally overcome dose-dependent midgut infection and midgut escape barriers (meb) m ... | 0 | 23331493 |
| a new rabies vaccine based on a recombinant orf virus (parapoxvirus) expressing the rabies virus glycoprotein. | the present study describes the generation of a new orf virus (orfv) recombinant, d1701-v-rabg, expressing the rabies virus (rabv) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus. one single immunization with recombinant orfv can stimulate high rabv-specific virus-neutralizing antibody (vna) titers in mice, cats, and dogs, representing all nonpermissive hosts for the orfv vector. the protectiv ... | 2012 | 23175365 |