Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
|---|
| venezuelan equine encephalitis virus disrupts stat1 signaling by distinct mechanisms independent of host shutoff. | venezuelan equine encephalitis virus (veev) is an important human and veterinary pathogen causing sporadic epizootic outbreaks of potentially fatal encephalitis. the type i interferon (ifn) system plays a central role in controlling veev and other alphavirus infections, and ifn evasion is likely an important determinant of whether these viruses disseminate and cause disease within their hosts. alphaviruses are thought to limit the induction of type i ifns and ifn-stimulated genes by shutting off ... | 2009 | 19656875 |
| the autophagy machinery is required to initiate hepatitis c virus replication. | in addition to its cellular homeostasis function, autophagy is emerging as a central component of antimicrobial host defense against diverse infections. to counteract this mechanism, many pathogens have evolved to evade, subvert, or exploit autophagy. here, we report that autophagy proteins (i.e., beclin-1, atg4b, atg5, and atg12) are proviral factors required for translation of incoming hepatitis c virus (hcv) rna and, thereby, for initiation of hcv replication, but they are not required once i ... | 2009 | 19666601 |
| comparison of monkeypox viruses pathogenesis in mice by in vivo imaging. | monkeypox viruses (mpxv) cause human monkeypox, a zoonotic smallpox-like disease endemic to africa, and are of worldwide public health and biodefense concern. using viruses from the congo (mpxv-2003-congo-358) and west african (mpxv-2003-usa-044) clades, we constructed recombinant viruses that express the luciferase gene (mpxv-congo/luc+and mpxv-usa-luc+) and compared their viral infection in mice by biophotonic imaging. balb/c mice became infected by both mpxv clades, but they recovered and cle ... | 2009 | 19668372 |
| viral strategies for studying the brain, including a replication-restricted self-amplifying delta-g vesicular stomatis virus that rapidly expresses transgenes in brain and can generate a multicolor golgi-like expression. | viruses have substantial value as vehicles for transporting transgenes into neurons. each virus has its own set of attributes for addressing neuroscience-related questions. here we review some of the advantages and limitations of herpes, pseudorabies, rabies, adeno-associated, lentivirus, and others to study the brain. we then explore a novel recombinant vesicular stomatitis virus (dg-vsv) with the g-gene deleted and transgenes engineered into the first position of the rna genome, which replicat ... | 2009 | 19672982 |
| multiple functions of precursor bdnf to cns neurons: negative regulation of neurite growth, spine formation and cell survival. | proneurotrophins and mature neurotrophins elicit opposite effects via the p75 neurotrophin receptor (p75(ntr)) and trk tyrosine kinase receptors, respectively; however the molecular roles of proneurotrophins in the cns are not fully understood. | 2009 | 19674479 |
| [construction and identification of replicon vector derived from an infectious full-length cdna clone of a sindbis virus]. | to construct vector system of xj-160 virus, a sindbis virus isolated in china, recombinant vector pbrepxj together with its helper plasmid pbr-h were derived from xj-160 viral infectious clone pbr-xj160 by overlap-pcr. to quantitatively and qualitatively verify the function of the replicon system, recombinant plasmids psinrep-egfp, pbrepxj-egfp, psinrep-r and pbrepxj-r were constructed by cloning report genes of enhanced green fluorescent protein (egfp) or renilla luciferase (r. luc) into pbrepx ... | 2009 | 19678570 |
| antiviral activity of innate immune protein isg15. | the host innate immune response, including the production of type-i ifn, represents the primary line of defense against invading viral pathogens. of the hundreds of ifn-stimulated genes (isgs) discovered to date, isg15 was one of the first identified and shown to encode a ubiquitin-like protein that functions, in part, as a modifier of protein function. evidence implicating isg15 as an innate immune protein with broad-spectrum antiviral activity continues to accumulate rapidly. this review will ... | 2009 | 19680460 |
| reverse genetics technology for rift valley fever virus: current and future applications for the development of therapeutics and vaccines. | the advent of reverse genetics technology has revolutionized the study of rna viruses, making it possible to manipulate their genomes and evaluate the effects of these changes on their biology and pathogenesis. the fundamental insights gleaned from reverse genetics-based studies over the last several years provide a new momentum for the development of designed therapies for the control and prevention of these viral pathogens. this review summarizes the successes and stumbling blocks in the devel ... | 2009 | 19682499 |
| characterization of chikungunya pseudotyped viruses: identification of refractory cell lines and demonstration of cellular tropism differences mediated by mutations in e1 glycoprotein. | chikungunya virus (chikv) is an alphavirus responsible for a number of large outbreaks. here we describe the efficient incorporation of chikv envelope glycoproteins into lentiviral and rhabdoviral particles. vectors pseudotyped with chikv envelope proteins efficiently transduced many cell types from different species. however, hematopoietic cell types were either partially or completely refractory. a mutation in e1 (a226v) has been linked with expansion of tropism for mosquito species, although ... | 2009 | 19692105 |
| e1 mutants identify a critical region in the trimer interface of the semliki forest virus fusion protein. | the alphavirus semliki forest virus (sfv) uses a membrane fusion reaction to infect host cells. fusion of the virus and cell membranes is triggered by low ph in the endosome and is mediated by the viral membrane protein e1. during fusion, e1 inserts into the target membrane, trimerizes, and refolds into a hairpin conformation. formation of the e1 homotrimer is critical to membrane fusion, but the mechanism of trimerization is not understood. the crystal structure of the postfusion e1 trimer show ... | 2009 | 19692469 |
| reverse genetic characterization of the natural genomic deletion in sars-coronavirus strain frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo. | during the outbreak of sars in 2002/3, a prototype virus was isolated from a patient in frankfurt/germany (strain frankfurt-1). as opposed to all other sars-coronavirus strains, frankfurt-1 has a 45-nucleotide deletion in the transmembrane domain of its orf 7b protein. when over-expressed in hek 293 cells, the full-length protein but not the variant with the deletion caused interferon beta induction and cleavage of procaspase 3. to study the role of orf 7b in the context of virus replication, we ... | 2009 | 19698190 |
| silencing viral microrna as a novel antiviral therapy? | viruses are intracellular parasites that ensure their existence by converting host cells into viral particle producing entities or into hiding places rendering the virus invisible to the host immune system. some viruses may also survive by transforming the infected cell into an immortal tumour cell. micrornas are small non-coding transcripts that function as posttranscriptional regulators of gene expression. viruses encode mirnas that regulate expression of both cellular and viral genes, and con ... | 2009 | 19704916 |
| [epidemic of pogosta disease--once again?]. | pogosta disease, manifesting itself as joint pain and rash, is an infection caused by sindbis virus. this virus circulates in nature and is occasionally transmitted to humans via mosquitoes. the incidence of antibodies to sindbis virus in the finnish population is approx. 5%, whereas in endemic regions of eastern finland it is several times higher in some places. globally, the prevalence of clinical infection is highest in finland, and the disease has emerged into an epidemic every seventh year. ... | 2009 | 19711594 |
| regulation of host translational machinery by african swine fever virus. | african swine fever virus (asfv), like other complex dna viruses, deploys a variety of strategies to evade the host's defence systems, such as inflammatory and immune responses and cell death. here, we analyse the modifications in the translational machinery induced by asfv. during asfv infection, eif4g and eif4e are phosphorylated (ser1108 and ser209, respectively), whereas 4e-bp1 is hyperphosphorylated at early times post infection and hypophosphorylated after 18 h. indeed, a potent increase i ... | 2009 | 19714237 |
| epistatic roles of e2 glycoprotein mutations in adaption of chikungunya virus to aedes albopictus and ae. aegypti mosquitoes. | between 2005 and 2007 chikungunya virus (chikv) caused its largest outbreak/epidemic in documented history. an unusual feature of this epidemic is the involvement of ae. albopictus as a principal vector. previously we have demonstrated that a single mutation e1-a226v significantly changed the ability of the virus to infect and be transmitted by this vector when expressed in the background of well characterized chikv strains lr2006 opy1 and 37997. however, in the current study we demonstrate that ... | 2009 | 19718263 |
| the phthalocyanine prototype derivative alcian blue is the first synthetic agent with selective anti-human immunodeficiency virus activity due to its gp120 glycan-binding potential. | alcian blue (ab), a phthalocyanine derivative, is able to prevent infection by a wide spectrum of human immunodeficiency virus type 1 (hiv-1), hiv-2, and simian immunodeficiency virus strains in various cell types [t cells, (co)receptor-transfected cells, and peripheral blood mononuclear cells]. with the exception of herpes simplex virus, ab is inactive against a broad variety of other (dna and rna) viruses. time-of-addition studies show that ab prevents hiv-1 infection at the virus entry stage, ... | 2009 | 19721061 |
| a structural and functional perspective of alphavirus replication and assembly. | alphaviruses are small, spherical, enveloped, positive-sense ssrna viruses responsible for a considerable number of human and animal diseases. alphavirus members include chikungunya virus, sindbis virus, semliki forest virus, the western, eastern and venezuelan equine encephalitis viruses, and the ross river virus. alphaviruses can cause arthritic diseases and encephalitis in humans and animals and continue to be a worldwide threat. the viruses are transmitted by blood-sucking arthropods, and re ... | 2009 | 19722838 |
| axonal elongation triggered by stimulus-induced local translation of a polarity complex protein. | during development, axon growth rates are precisely regulated to provide temporal control over pathfinding. the precise temporal regulation of axonal growth is a key step in the formation of functional synapses and the proper patterning of the nervous system. the rate of axonal elongation is increased by factors such as netrin-1 and nerve growth factor (ngf), which stimulate axon outgrowth using incompletely defined pathways. to clarify the mechanism of netrin-1- and ngf-stimulated axon growth, ... | 2009 | 19620967 |
| performance of the realstar chikungunya virus real-time reverse transcription-pcr kit. | a novel commercial chikungunya virus real-time reverse transcription-pcr (rt-pcr) kit was evaluated on a comprehensive panel of original patient samples. the assay was 100% sensitive and specific in comparison to a published real-time rt-pcr. viral loads from both assays were highly correlated. the kit proved to be suitable for routine use in patient care. | 2009 | 19625474 |
| ars2 regulates both mirna- and sirna- dependent silencing and suppresses rna virus infection in drosophila. | intrinsic immune responses autonomously inhibit viral replication and spread. one pathway that restricts viral infection in plants and insects is rna interference (rnai), which targets and degrades viral rna to limit infection. to identify additional genes involved in intrinsic antiviral immunity, we screened drosophila cells for modulators of viral infection using an rnai library. we identified ars2 as a key component of drosophila antiviral immunity. loss of ars2 in cells, or in flies, increas ... | 2009 | 19632183 |
| west nile virus infection alters midgut gene expression in culex pipiens quinquefasciatus say (diptera: culicidae). | alterations in gene expression in the midgut of female culex pipiens quinquefasciatus exposed to blood meals containing 6.8 logs plaque-forming units/ml of west nile virus (wnv) were studied by fluorescent differential display. twenty-six different cdnas exhibited reproducible differences after feeding on infected blood. of these, 21 cdnas showed an increase in expression, and 5 showed a decrease in expression as a result of wnv presence in the blood meal. genbank database searches showed that o ... | 2009 | 19635880 |
| regulation of the proteasome by neuronal activity and calcium/calmodulin-dependent protein kinase ii. | protein degradation via the ubiquitin proteasome system has been shown to regulate changes in synaptic strength that underlie multiple forms of synaptic plasticity. it is plausible, therefore, that the ubiquitin proteasome system is itself regulated by synaptic activity. by utilizing live-cell imaging strategies we report the rapid and dynamic regulation of the proteasome in hippocampal neurons by synaptic activity. we find that the blockade of action potentials (aps) with tetrodotoxin inhibited ... | 2009 | 19638347 |
| oncolytic activity of sindbis virus in human oral squamous carcinoma cells. | sindbis virus (sin) infection causes no or only mild symptoms (fever, rash, and arthralgia) in humans. however, sin has a strong cytopathic effect (cpe) on various cancer cells. this study focuses on the oncolytic activity of sin ar399 on oral cancer cells compared with reovirus, a well-known oncolytic virus that targets cancer cells. | 2009 | 19638980 |
| similarities and differences in antagonism of neuron alpha/beta interferon responses by venezuelan equine encephalitis and sindbis alphaviruses. | venezuelan equine encephalitis virus (veev) is highly virulent in adult laboratory mice, while sindbis virus (sinv) is avirulent regardless of dose or inoculation route, dependent upon functioning alpha/beta interferon (ifn-alpha/beta) responses. we have examined each virus' resistance to and/or antagonism of ifn-alpha/beta responses in neurons, a cell type targeted by both viruses in mice, by infecting ifn-alpha/beta-treated or untreated primary cultures with viruses or virus-derived replicons ... | 2009 | 19641001 |
| type i interferon induction is correlated with attenuation of a south american eastern equine encephalitis virus strain in mice. | north american eastern equine encephalitis virus (na-eeev) strains cause high mortality in humans, whereas south american strains (sa-eeev) are typically avirulent. to clarify mechanisms of sa-eeev attenuation, we compared mouse-attenuated bear436087 sa-eeev, considered an eeev vaccine candidate, with mouse-virulent na-eeev strain, fl93-939. although attenuated, bear436087 initially replicated more efficiently than fl93-939 in lymphoid and other tissues, inducing systemic ifn-alpha/beta release, ... | 2009 | 19539968 |
| roles of stargazin and phosphorylation in the control of ampa receptor subcellular distribution. | understanding how the subcellular fate of newly synthesized ampa receptors (ampars) is controlled is important for elucidating the mechanisms of neuronal function. we examined the effect of increased synthesis of ampar subunits on their subcellular distribution in rat hippocampal neurons. virally expressed ampar subunits (glur1 or glur2) accumulated in cell bodies and replaced endogenous dendritic ampar with little effect on total dendritic amounts and caused no change in synaptic transmission. ... | 2009 | 19543281 |
| intravenous inoculation of a bat-associated rabies virus causes lethal encephalopathy in mice through invasion of the brain via neurosecretory hypothalamic fibers. | the majority of rabies virus (rv) infections are caused by bites or scratches from rabid carnivores or bats. usually, rv utilizes the retrograde transport within the neuronal network to spread from the infection site to the central nervous system (cns) where it replicates in neuronal somata and infects other neurons via trans-synaptic spread. we speculate that in addition to the neuronal transport of the virus, hematogenous spread from the site of infection directly to the brain after accidental ... | 2009 | 19543379 |
| rapid, long-term labeling of cells in the developing and adult rodent visual cortex using double-stranded adeno-associated viral vectors. | chronic in vivo imaging studies of the brain require a labeling method that is fast, long-lasting, efficient, nontoxic, and cell-type specific. over the last decade, adeno-associated virus (aav) has been used to stably express fluorescent proteins in neurons in vivo. however, aav's main limitation for many studies (such as those of neuronal development) is the necessity of second-strand dna synthesis, which delays peak transgene expression. the development of double-stranded aav (dsaav) vectors ... | 2009 | 19551873 |
| characterization of a novel flavivirus from mosquitoes in northern europe that is related to mosquito-borne flaviviruses of the tropics. | a novel flavivirus was isolated from mosquitoes in finland, representing the first mosquito-borne flavivirus from northern europe. the isolate, designated lammi virus (lamv), was antigenically cross-reactive with other flaviviruses and exhibited typical flavivirus morphology as determined by electron microscopy. the genomic sequence of lamv was highly divergent from the recognized flaviviruses, and yet the polyprotein properties resembled those of mosquito-borne flaviviruses. phylogenetic analys ... | 2009 | 19570865 |
| random insertion mutagenesis of sindbis virus nonstructural protein 2 and selection of variants incapable of downregulating cellular transcription. | sindbis virus nonstructural protein 2 (sinv nsp2) is an important determinant of virus pathogenesis and downregulation of virus-induced cell response. this protein efficiently inhibits transcription of cellular messenger and ribosomal rnas and, thus, is capable of inhibiting the activation of genes whose products are involved in development of the antiviral response. alphavirus nsp2 has a number of predicted functional domains, some of which were confirmed by crystal structure. our current study ... | 2009 | 19570872 |
| functional analysis of the bunyamwera orthobunyavirus gc glycoprotein. | the virion glycoproteins gn and gc of bunyamwera orthobunyavirus (family bunyaviridae) are encoded by the m rna genome segment and have roles in both viral attachment and membrane fusion. to investigate further the structure and function of the gc protein in viral replication, we generated 12 mutants that contain truncations from the n terminus. the effects of these deletions were analysed with regard to golgi targeting, low ph-dependent membrane fusion, infectious virus-like particle (vlp) form ... | 2009 | 19570952 |
| rnai targeting of west nile virus in mosquito midguts promotes virus diversification. | west nile virus (wnv) exists in nature as a genetically diverse population of competing genomes. this high genetic diversity and concomitant adaptive plasticity has facilitated the rapid adaptation of wnv to north american transmission cycles and contributed to its explosive spread throughout the new world. wnv is maintained in nature in a transmission cycle between mosquitoes and birds, with intrahost genetic diversity highest in mosquitoes. the mechanistic basis for this increase in genetic di ... | 2009 | 19578437 |
| differential incorporation of cholesterol by sindbis virus grown in mammalian or insect cells. | cholesterol has been shown to be essential for the fusion of alphaviruses with artificial membranes (liposomes). cholesterol has also been implicated as playing an essential and critical role in the processes of entry and egress of alphaviruses in living cells. paradoxically, insects, the alternate host for alphaviruses, are cholesterol auxotrophs and contain very low levels of this sterol. to further evaluate the role of cholesterol in the life cycle of alphaviruses, the cholesterol levels of t ... | 2009 | 19587056 |
| specific transduction of hiv-susceptible cells for ccr5 knockdown and resistance to hiv infection: a novel method for targeted gene therapy and intracellular immunization. | hiv-1 gene therapy offers a promising alternative to small molecule antiretroviral treatments and current vaccination strategies by transferring, into hiv-1-susceptible cells, the genetic ability to resist infection. the need for novel and innovative strategies to prevent and treat hiv-1 infection is critical due to devastating effects of the virus in developing countries, high cost, toxicity, generation of escape mutants from antiretroviral therapies, and the failure of past and current vaccina ... | 2009 | 19593160 |
| apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection. | many viruses, including picornaviruses, have the potential to infect the central nervous system (cns) and stimulate a neuroinflammatory immune response, especially in infants and young children. cognitive deficits associated with cns picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a ... | 2009 | 19608874 |
| coordinated changes in dendritic arborization and synaptic strength during neural circuit development. | neural circuit development requires concurrent morphological and functional changes. here, we identify coordinated and inversely correlated changes in dendritic morphology and mepsc amplitude following increased neural activity. we show that overexpression of beta-catenin, a molecule that increases total dendritic length, mimics the effects of increased neuronal activity by scaling down mepsc amplitudes, while postsynaptic expression of a protein that sequesters beta-catenin reverses the effects ... | 2009 | 19146814 |
| apoptosis in animal models of virus-induced disease. | apoptosis is associated with virus-induced human diseases of the central nervous system, heart and liver, and causes substantial morbidity and mortality. although virus-induced apoptosis is well characterized in individual cells in cell culture, virus-induced apoptosis in vivo and the role of apoptosis in virus-induced disease is not well established. this review focuses on animal models of virus-induced diseases of the central nervous system, heart and liver that provide insights into the role ... | 2009 | 19148180 |
| targeted transduction of cd34+ hematopoietic progenitor cells in nonpurified human mobilized peripheral blood mononuclear cells. | conventional gene-therapy applications of hematopoietic stem cells (hscs) involve purification of cd34+ progenitor cells from the mobilized peripheral blood, ex vivo transduction of the gene of interest into them, and reinfusion of the transduced cd34+ progenitor cells into patients. eliminating the process of purification would save labor, time and money, while enhancing hscs viability, transplantability and pluripotency. lentiviral vectors have been widely used in gene therapy because they inf ... | 2009 | 19152374 |
| an alphavirus replicon-derived candidate vaccine against rift valley fever virus. | rift valley fever virus (rvfv) is a mosquito-transmitted bunyavirus (genus phlebovirus) associated with severe disease in livestock and fatal encephalitis or haemorrhagic fever in a proportion of infected humans. although live attenuated and inactivated vaccines have been used in livestock, and on a limited scale in humans, there is a need for improved anti-rvfv vaccines. towards this goal, sindbis virus replicon vectors expressing the rvfv gn and gc glycoproteins, as well as the non-structural ... | 2009 | 19171081 |
| in vitro activity and preclinical profile of tmc435350, a potent hepatitis c virus protease inhibitor. | the hepatitis c virus (hcv) ns3/4a serine protease has been explored as a target for the inhibition of viral replication in preclinical models and in hcv-infected patients. tmc435350 is a highly specific and potent inhibitor of ns3/4a protease selected from a series of novel macrocyclic inhibitors. in biochemical assays using ns3/4a proteases of genotypes 1a and 1b, inhibition constants of 0.5 and 0.4 nm, respectively, were determined. tmc435350 inhibited hcv replication in a cellular assay (sub ... | 2009 | 19171797 |
| two types of thalamocortical projections from the motor thalamic nuclei of the rat: a single neuron-tracing study using viral vectors. | the axonal arborization of single motor thalamic neurons was examined in rat brain using a viral vector expressing membrane-targeted palmitoylation site-attached green fluorescent protein (palgfp). we first divided the ventral anterior-ventral lateral motor thalamic nuclei into 1) the rostromedial portion, which was designated inhibitory afferent-dominant zone (iz) with intense glutamate decarboxylase immunoreactivity and weak vesicular glutamate transporter 2 immunoreactivity, and 2) the caudol ... | 2009 | 19174446 |
| noncytolytic clearance of sindbis virus infection from neurons by gamma interferon is dependent on jak/stat signaling. | the alphavirus sindbis virus (sinv) causes encephalomyelitis in mice by infecting neurons of the brain and spinal cord. the outcome is age dependent. young animals develop fatal disease, while older animals recover from infection. recovery requires noncytolytic clearance of sinv from neurons, and gamma interferon (ifn-gamma) is an important contributor to clearance in vivo. ifn-gamma-dependent clearance has been studied using immortalized csm14.1 rat neuronal cells that can be differentiated in ... | 2009 | 19176616 |
| learning from the viral journey: how to enter cells and how to overcome intracellular barriers to reach the nucleus. | viruses deliver their genome into host cells where they subsequently replicate and multiply. a variety of relevant strategies have evolved by which viruses gain intracellular access and utilize cellular machinery for the synthesis of their genome. therefore, the viral journey provides insight into the cell's trafficking machinery and how it can be best exploited to improve nonviral gene delivery systems. this review summarizes viral internalization pathways and intracellular trafficking of virus ... | 2009 | 19194803 |
| creation of interferon-alpha8 mutants with amino acid substitutions against interferon-alpha receptor-2 binding sites using phage display system and evaluation of their biologic properties. | in this study, we describe the creation of three interferon-alpha (ifn-alpha)8 mutants with markedly higher antiviral and antiproliferative activities in comparison with those of the wild-type (wt)ifn-alpha8, wtifn-alpha2, and ifn-con1 using a phage display system. sequence analysis showed that three out of the six hot-spot amino acid residues of wtifn-alpha8 known to be important for the interaction with the ifn-alpha receptor-2 (ifnar-2)-binding sites were substituted to other amino acids and ... | 2009 | 19196068 |
| lrp/lr as an alternative promising target in therapy of prion diseases, alzheimer's disease and cancer. | the 37 kda/67 kda laminin receptor (lrp/lr) represents a key player for cell adhesion, is associated with the metastatic potential of solid tumors and is required for maintenance of cell viability by preventing apoptosis. lrp/lr acts as a receptor for viruses such as sindbis virus, venezuelean equine encephalitis (vee) virus, adeno-associated-viruses (aav) and dengue virus, the latter causing 50 to 100 million infections in humans per year. lrp/lr acts further as a receptor for prions and repres ... | 2009 | 19200017 |
| an improved in vitro and in vivo sindbis virus expression system through host and virus engineering. | the sindbis viral expression system enables the rapid production of high levels of recombinant protein in mammalian cells; however, this expression is typically limited to transient production due to the cytotoxicity of the virus. limiting the lethality inherent in the sindbis virus vector in order to enable long term, sustained expression of recombinant proteins may be possible. in this study, modifications to virus and host have been combined in order to reduce the cytopathic effects. non-cyto ... | 2009 | 19200810 |
| antiviral immunity in drosophila requires systemic rna interference spread. | multicellular organisms evolved sophisticated defence systems to confer protection against pathogens. an important characteristic of these immune systems is their ability to act both locally at the site of infection and at distal uninfected locations. in insects, such as drosophila melanogaster, rna interference (rnai) mediates antiviral immunity. however, the antiviral rnai defence in flies seems to be a local, cell-autonomous process, as flies are thought to be unable to generate a systemic rn ... | 2009 | 19204732 |
| gamma-herpesvirus-induced protection against bacterial infection is transient. | herpesviruses are widely disseminated in the population and establish lifelong latency, which is associated with a variety of pathological consequences. a recent report showed that mice latently infected with either murine gamma-herpesvirus-68 (gammahv68) or murine cytomegalovirus (mcmv), mouse pathogens genetically similar to the human herpesviruses, epstein-barr virus, kaposi's sarcoma-associated herpesvirus, and cytomegalovirus, had enhanced resistance to subsequent bacterial infection, sugge ... | 2009 | 19210230 |
| apoptosis in murine norovirus-infected raw264.7 cells is associated with downregulation of survivin. | noroviruses (nvs) are recognized as a major cause of nonbacterial gastroenteritis in humans. studies of the human nvs continue to be hampered by the inability to propagate them in any cell culture system. until recently, most data concerning nv replication were derived from studies of feline calicivirus and rabbit hemorrhagic disease virus, which are cultivable members of the family caliciviridae. from such studies, it was proposed that caliciviruses induce apoptosis to facilitate the disseminat ... | 2009 | 19211757 |
| dengue virus type 2 infections of aedes aegypti are modulated by the mosquito's rna interference pathway. | a number of studies have shown that both innate and adaptive immune defense mechanisms greatly influence the course of human dengue virus (denv) infections, but little is known about the innate immune response of the mosquito vector aedes aegypti to arbovirus infection. we present evidence here that a major component of the mosquito innate immune response, rna interference (rnai), is an important modulator of mosquito infections. the rnai response is triggered by double-stranded rna (dsrna), whi ... | 2009 | 19214215 |
| caspase inhibitor p35 is required for the production of robust baculovirus virions in trichoplusia ni tn-368 cells. | apoptosis can protect lepidopteran insects against baculovirus infection by limiting viral replication. baculoviruses counter this response by expressing anti-apoptotic proteins such as the caspase inhibitor p35, which is expressed by several baculoviruses including autographa californica mutiple nucleopolyhedrovirus (acmnpv). mutants of acmnpv that lack the p35 gene induce apoptosis in spodoptera frugiperda cells, and replication of these mutants is severely curtailed in s. frugiperda cell line ... | 2009 | 19218211 |
| characterization of a mimivirus rna cap guanine-n2 methyltransferase. | a 2,2,7-trimethylguanosine (tmg) cap is a signature feature of eukaryal snrnas, telomerase rnas, and trans-spliced nematode mrnas. tmg and 2,7-dimethylguanosine (dmg) caps are also present on mrnas of two species of alphaviruses (positive strand rna viruses of the togaviridae family). it is presently not known how viral mrnas might acquire a hypermethylated cap. mimivirus, a giant dna virus that infects amoeba, encodes many putative enzymes and proteins implicated in rna transactions, including ... | 2009 | 19218551 |
| low-density macroarray for rapid detection and identification of crimean-congo hemorrhagic fever virus. | crimean-congo hemorrhagic fever (cchf) is a tick-borne viral zoonosis which occurs throughout africa, eastern europe, and asia and results in an approximately 30% fatality rate. a reverse transcription-pcr assay including a competitive internal control was developed on the basis of the most up-to-date genome information. biotinylated amplification products were hybridized to dna macroarrays on the surfaces of polymer supports, and hybridization events were visualized by incubation with a strepta ... | 2009 | 19225100 |
| the regulation of disassembly of alphavirus cores. | alphaviruses are used as model viruses for structure determination and for analysis of virus entry. they are used also as vectors for protein expression and gene therapy. virus particles are assembled by budding, using preformed cores and a modified cellular membrane. during entry, alphaviruses release the viral core into the cytoplasm. cores are disassembled during virus entry and accumulate in the cytoplasm during virus multiplication. the regulation of core disassembly is the subject of this ... | 2009 | 19225713 |
| role of bnip3 and nix in cell death, autophagy, and mitophagy. | bnip3 and nix are proteins related to the bh3-only family, which induce both cell death and autophagy. consistent with their ability to induce cell death, bnip3 and nix are implicated in the pathogenesis of cancer and heart disease. in tumor cells, bnip3 and nix are regulated by hypoxia, and the deregulation of bnip3 or nix expression is associated with tumor growth. in heart muscle, bnip3 and nix are regulated by hypoxia and galphaq-dependent signaling, respectively, and their expression is ass ... | 2009 | 19229244 |
| the nsp3 macro domain is important for sindbis virus replication in neurons and neurovirulence in mice. | sindbis virus (sinv), the prototype alphavirus, contains a macro domain in the highly conserved n-terminal region of nonstructural protein 3 (nsp3). however, the biological role of the macro domain is unclear. mutations of amino acids 10 and 24 from asparagine to alanine in the adp-ribose binding region of the macro domain impaired sinv replication and viral rna synthesis particularly in neurons, but did not alter binding of poly(adp-ribose). mutation at position 10 had the greatest effect and c ... | 2009 | 19395054 |
| adenovirus vectors expressing hantavirus proteins protect hamsters against lethal challenge with andes virus. | hantaviruses infect humans following aerosolization from rodent feces and urine, producing hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. due to the high rates of mortality and lack of therapies, vaccines are urgently needed. nonreplicating adenovirus (ad) vectors that express andes hantavirus (andv) nucleocapsid protein (adn) or glycoproteins (adg(n) and adg(c)) were constructed. ad vectors were tested for their ability to protect syrian hamsters from a lethal andv inf ... | 2009 | 19403663 |
| virulence variation among isolates of western equine encephalitis virus in an outbred mouse model. | little is known about viral determinants of virulence associated with western equine encephalitis virus (weev). here, we have analysed six north american weev isolates in an outbred cd1 mouse model. full genome sequence analyses showed < or =2.7 % divergence among the six weev isolates. however, the percentage mortality and mean time to death (mtd) varied significantly when mice received subcutaneous injections of 10(3) p.f.u. of each virus. two weev strains, mcmillan (mcm) and imperial 181 (imp ... | 2009 | 19403754 |
| salmonella enterica serovar typhi live vector vaccines finally come of age. | attenuated salmonella typhi vaccine strains hold great promise as live vectors for presentation of foreign antigens from unrelated bacterial, viral and parasitic pathogens to the immune system. although this approach has proved quite successful in experimental animal models for eliciting antigen-specific mucosal, humoral and cellular responses, results have been disappointing for clinical trials carried out thus far. we hypothesize that the paucity of human responses to foreign antigens delivere ... | 2009 | 19417771 |
| the n-terminal domain of glud2 (glurdelta2) recruits presynaptic terminals and regulates synaptogenesis in the cerebellum in vivo. | the delta2 glutamate receptor (glurdelta2; glud2), which is predominantly expressed on postsynaptic sites at parallel fiber (pf)-purkinje cell synapses in the cerebellum, plays two crucial roles in the cerebellum: the formation of pf synapses and the regulation of long-term depression (ltd), a form of synaptic plasticity underlying motor learning. although the induction of ltd and motor learning absolutely require signaling via the cytoplasmic c-terminal domain of glud2, the mechanisms by which ... | 2009 | 19420242 |
| selection and characterization of packaging cell lines for xj-160 virus. | xj-160 virus is a mosquito-derived sindbis-like virus isolated in china. based on its infectious clone (pbr-xj-160) we have developed an rna-based vector system. in this work, we constructed packaging cell lines (pcls) for xj-160 virus. | 2009 | 19420962 |
| effects of the nsp2-726 pro mutation on infectivity and pathogenesis of sindbis virus derived from a full-length infectious cdna clone. | the point mutations at residue 726 pro in the nonstructural gene 2 (nsp2-726p) could make sindbis virus (sinv) replicons lacking the structural protein-coding region less cytopathic and capable of persisting in some vertebrate cell lines. however, the effects of nsp2-726p mutations on characteristics of sinv in the context of genomic-rna are poorly understood. to investigate the effects of point mutations at nsp2-726p on the infectivity and the pathogenesis of sinv, based on the infectious clone ... | 2009 | 19428754 |
| redirecting lentiviral vectors by insertion of integrin-tageting peptides into envelope proteins. | targeting gene therapy vectors that can home in on desired cell and tissue types in vivo comprise the ultimate gene delivery system. we have previously developed targeting lentiviral vectors by pseudotyping vectors with modified sindbis virus envelope proteins. the envelope protein contains the fc-binding region of protein a (zz domain), so the virus can be conjugated with antibodies. the conjugated antibody mediates specific transduction of the cells and tissues expressing the target antigens, ... | 2009 | 19434609 |
| laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. | a diverse array of infectious agents, including prions and certain neurotropic viruses, bind to the laminin receptor (lr), and this determines tropism to the cns. bacterial meningitis in childhood is almost exclusively caused by the respiratory tract pathogens streptococcus pneumoniae, neisseria meningitidis, and haemophilus influenzae, but the mechanism by which they initiate contact with the vascular endothelium of the blood brain barrier (bbb) is unknown. we hypothesized that an interaction w ... | 2009 | 19436113 |
| counteracting quasispecies adaptability: extinction of a ribavirin-resistant virus mutant by an alternative mutagenic treatment. | lethal mutagenesis, or virus extinction promoted by mutagen-induced elevation of mutation rates of viruses, may meet with the problem of selection of mutagen-resistant variants, as extensively documented for standard, non-mutagenic antiviral inhibitors. previously, we characterized a mutant of foot-and-mouth disease virus that included in its rna-dependent rna polymerase replacement m296i that decreased the sensitivity of the virus to the mutagenic nucleoside analogue ribavirin. | 2009 | 19436746 |
| signal transduction pathways in liver and the influence of hepatitis c virus infection on their activities. | in liver, the most intensively studied transmembrane and intracellular signal transduction pathways are the janus kinase signal transduction pathway, the mitogen-activated protein kinases signal transduction pathway, the transforming growth factor beta signal transduction pathway, the tumor necrosis factor alpha signal transduction pathway and the recently discovered sphingolipid signal transduction pathway. all of them are activated by many different cytokines and growth factors. they regulate ... | 2009 | 19437557 |
| activity level-dependent synapse-specific ampa receptor trafficking regulates transmission kinetics. | central glutamatergic synapses may express ampa-sensitive glutamate receptors (ampa-rs) with distinct gating properties and exhibit different transmission dynamics, which are important for computing various synaptic inputs received at different populations of synapses. however, how glutamatergic synapses acquire ampa-rs with distinct kinetics to influence synaptic integration remains poorly understood. here i report synapse-specific trafficking of distinct ampa-rs in rat cortical layer 4 stellat ... | 2009 | 19439609 |
| chimeric alphavirus vaccine candidates protect mice from intranasal challenge with western equine encephalitis virus. | we developed two types of chimeric sindbis virus (sinv)/western equine encephalitis virus (weev) alphaviruses to investigate their potential use as live virus vaccines against wee. the first-generation vaccine candidate, sin/co92, was derived from structural protein genes of weev strain co92-1356, and two second-generation candidates were derived from weev strain mcmillan. for both first- and second-generation vaccine candidates, the nonstructural protein genes were derived from sinv strain ar33 ... | 2009 | 19446595 |
| cd4+ t cells provide protection against acute lethal encephalitis caused by venezuelan equine encephalitis virus. | studying the mechanisms of host survival resulting from viral encephalitis is critical to the development of vaccines. here we have shown in several independent studies that high dose treatment with neutralizing antibody prior to intranasal infection with venezuelan equine encephalitis virus had an antiviral effect in the visceral organs and prolonged survival time of infected mice, even in the absence of alphabeta t cells. nevertheless, antibody treatment did not prevent the development of leth ... | 2009 | 19446933 |
| targeted gene delivery to cd117-expressing cells in vivo with lentiviral vectors co-displaying stem cell factor and a fusogenic molecule. | the development of a lentiviral system to deliver genes to specific cell types could improve the safety and the efficacy of gene delivery. previously, we have developed an efficient method to target lentivectors to specific cells via an antibody-antigen interaction in vitro and in vivo. we report herein a targeted lentivector that harnesses the natural ligand-receptor recognition mechanism for targeted modification of c-kit receptor-expressing cells. for targeting, we incorporate membrane-bound ... | 2009 | 19452500 |
| a versatile targeting system with lentiviral vectors bearing the biotin-adaptor peptide. | targeted gene transduction in vivo is the ultimate preferred method for gene delivery. we previously developed targeting lentiviral vectors that specifically recognize cell surface molecules with conjugated antibodies and mediate targeted gene transduction both in vitro and in vivo. although effective in some experimental settings, the conjugation of virus with antibodies is mediated by the interaction between protein a and the fc region of antibodies, which is not as stable as covalent conjugat ... | 2009 | 19455593 |
| alpha-c-galactosylceramide as an adjuvant for a live attenuated influenza virus vaccine. | there is a substantial need to develop better influenza virus vaccines that can protect populations that are not adequately protected by the currently licensed vaccines. while live attenuated influenza virus vaccines induce superior immune responses compared to inactivated vaccines, the manufacturing process of both types of influenza virus vaccines is time consuming and may not be adequate during a pandemic. adjuvants would be particularly useful if they could enhance the immune response to liv ... | 2009 | 19464560 |
| nv-128, a novel isoflavone derivative, induces caspase-independent cell death through the akt/mammalian target of rapamycin pathway. | resistance to apoptosis is 1 of the key events that confer chemoresistance and is mediated by the overexpression of antiapoptotic proteins, which inhibit caspase activation. the objective of this study was to evaluate whether the activation of an alternative, caspase-independent cell death pathway could promote death in chemoresistant ovarian cancer cells. the authors report the characterization of nv-128 as an inducer of cell death through a caspase-independent pathway. | 2009 | 19472400 |
| chemically inducible inactivation of protein synthesis in genetically targeted neurons. | 2009 | 19474302 | |
| sindbis virus as a model for studies of conformational changes in a metastable virus and the role of conformational changes in in vitro antibody neutralisation. | sindbis virus has long been the prototypical alphavirus used in the study of assembly of icosahedral viruses which contain membranes. much is known about the assembly pathway and molecular architecture of this virus, and models of mechanisms of infection and release of the viral rna have been proposed. this review will focus on the structural aspects of in vitro antibody neutralisation of a metastable alphavirus, sindbis virus, which results from antibody induced conformational changes. for the ... | 2009 | 19475572 |
| a therapeutic antibody against west nile virus neutralizes infection by blocking fusion within endosomes. | defining the precise cellular mechanisms of neutralization by potently inhibitory antibodies is important for understanding how the immune system successfully limits viral infections. we recently described a potently inhibitory monoclonal antibody (mab e16) against the envelope (e) protein of west nile virus (wnv) that neutralizes infection even after virus has spread to the central nervous system. herein, we define its mechanism of inhibition. e16 blocks infection primarily at a post-attachment ... | 2009 | 19478866 |
| nora virus persistent infections are not affected by the rnai machinery. | drosophila melanogaster is widely used to decipher the innate immune system in response to various pathogens. the innate immune response towards persistent virus infections is among the least studied in this model system. we recently discovered a picorna-like virus, the nora virus which gives rise to persistent and essentially symptom-free infections in drosophila melanogaster. here, we have used this virus to study the interaction with its host and with some of the known drosophila antiviral im ... | 2009 | 19478998 |
| engineering fusogenic molecules to achieve targeted transduction of enveloped lentiviral vectors. | lentiviral vectors with broad tropism are one of the most promising gene delivery systems capable of efficiently delivering genes of interest into both dividing and non-dividing cells while maintaining long-term transgene expression. however, there are needs for developing lentiviral vectors with the capability to deliver genes to specific cell types, thus reducing the "off-target" effect of gene therapy. in the present study, we investigated the possibility of engineering the fusion-active doma ... | 2009 | 19490632 |
| effect of sequential exposure on infection and dissemination rates for west nile and st. louis encephalitis viruses in culex quinquefasciatus. | west nile virus has spread rapidly throughout the united states since its introduction in 1999, into some areas that are also endemic for st. louis encephalitis virus (slev). these viruses are in the same antigenic complex within the genus flavivirus, family flaviviridae. further, both viruses are transmitted primarily by culex spp. mosquitoes and use birds as amplifying hosts. these viruses could contemporaneously coinfect individual vectors wherein changes in mosquito immune responses might oc ... | 2009 | 19492941 |
| saag-4 is a novel mosquito salivary protein that programmes host cd4 t cells to express il-4. | mosquitoes represent the most important vector for transmitting pathogens that cause human disease. central to pathogen transmission is the ability to divert the host immune system away from th1 and towards th2 responsiveness. identification of the mosquito factor(s) critical for programming th2 responsiveness should therefore lead to strategies to neutralize their function and thus prevent disease transmission. in the current study, we used a tcr transgenic adoptive transfer system to screen ge ... | 2009 | 19493208 |
| dynamics of biologically active subpopulations of influenza virus: plaque-forming, noninfectious cell-killing, and defective interfering particles. | the dynamic changes in the temporal appearance and quantity of a new class of influenza virus, noninfectious cell-killing particles (nickp), were compared to defective interfering particles (dip). after a single high-multiplicity passage in mdck cells of an egg-derived stock that lacked detectable nickp or dip, both classes of particles appeared in large numbers (>5 x 10(8)/ml), and the plaque-forming particle (pfp) titer dropped approximately 60-fold. after two additional serial high-multiplici ... | 2009 | 19494019 |
| n-linked glycans on dengue viruses grown in mammalian and insect cells. | this study compared the ability of mosquito and mammalian cell-derived dengue virus (denv) to infect human dendritic cell-specific icam3-grabbing non-integrin (dc-sign)-expressing cells and characterized the structure of envelope (e) protein n-linked glycans on denv derived from the two cell types. denvs derived from both cell types were equally effective at infecting dc-sign-expressing human monocytes and dendritic cells. the n-linked glycans on mosquito cell-derived virus were a mix of high-ma ... | 2009 | 19494052 |
| effective suppression of dengue fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome. | outbreaks of dengue impose a heavy economic burden on developing countries in terms of vector control and human morbidity. effective vaccines against all four serotypes of dengue are in development, but population replacement with transgenic vectors unable to transmit the virus might ultimately prove to be an effective approach to disease suppression, or even eradication. a key element of the refractory transgenic vector approach is the development of transgenes that effectively prohibit viral t ... | 2009 | 19497123 |
| foot-and-mouth disease virus neutralizing antibodies production induced by pcdna3 and sindbis virus based plasmid encoding fmdv p1-2a3c3d in swine. | dna vaccination against foot-and-mouth disease virus (fmdv) is an attractive and alternative strategy to the use of classical inactivated viral vaccines. the injection of a pcdna3.1-based dna vaccine encoding for fmdv p1-2a3c3d and gm-csf proteins had previously been shown to induce the production of neutralizing antibodies against fmdv and partially protect swine against an experimental challenge. based on the induction of fmdv humoral immune responses, the aim of the present study was to see i ... | 2009 | 19501256 |
| progress on the development of therapeutics against west nile virus. | a decade has passed since the appearance of west nile virus (wnv) in humans in the western hemisphere in new york city. during this interval, wnv spread inexorably throughout north and south america and caused millions of infections ranging from a sub-clinical illness, to a self-limiting febrile syndrome or lethal neuroinvasive disease. its entry into the united states triggered intensive research into the basic biology of wnv and the elements that comprise a protective host immune response. alt ... | 2009 | 19501622 |
| mosquitoes put the brake on arbovirus evolution: experimental evolution reveals slower mutation accumulation in mosquito than vertebrate cells. | like other arthropod-borne viruses (arboviruses), mosquito-borne dengue virus (denv) is maintained in an alternating cycle of replication in arthropod and vertebrate hosts. the trade-off hypothesis suggests that this alternation constrains denv evolution because a fitness increase in one host usually diminishes fitness in the other. moreover, the hypothesis predicts that releasing denv from host alternation should facilitate adaptation. to test this prediction, denv was serially passaged in eith ... | 2009 | 19503824 |
| a strongly transdominant mutation in the human immunodeficiency virus type 1 gag gene defines an achilles heel in the virus life cycle. | the human immunodeficiency virus type 1 (hiv-1) protease (pr) makes five obligatory cleavages in the viral gag polyprotein precursor. the cleavage events release the virion structural proteins from the precursor and allow the virion to undergo maturation to become infectious. the protease cleavage between the matrix protein (ma) domain and the adjacent capsid protein (ca) domain releases ca from the membrane-anchored ma and allows the n terminus of ca to refold into a structure that facilitates ... | 2009 | 19515760 |
| structural and functional elements of the promoter encoded by the 5' untranslated region of the venezuelan equine encephalitis virus genome. | venezuelan equine encephalitis virus (veev) is one of the most pathogenic members of the alphavirus genus in the togaviridae family. the pathogenesis of this virus depends strongly on the sequences of the structural proteins and on the mutations in the rna promoter encoded by the 5' untranslated region (5'utr) of the viral genome. in this study, we performed a detailed investigation of the structural and functional elements of the 5'-terminal promoter and analyzed the effect of multiple mutation ... | 2009 | 19515761 |
| fate of minus-strand templates and replication complexes produced by a p23-cleavage-defective mutant of sindbis virus. | sin2v is an engineered mutant sindbis virus (sin) that is unable to process the p23 cleavage site in polyproteins p123 and p1234 that are translated from the genome after its entry into cells. unlike wild-type (wt) sin, it caused minus strands to be made continuously and replication-transcription complex (rtc) activity to be unstable (r. gorchakov, e. frolova, s. sawicki, s. atasheva, d. sawicki, and i. frolov, j. virol. 82:6218-6231, 2008). we examined further the effects of p23 on sin rna repl ... | 2009 | 19515769 |
| interaction of sindbis virus non-structural protein 3 with poly(adp-ribose) polymerase 1 in neuronal cells. | the alphavirus non-structural protein 3 (nsp3) has a conserved n-terminal macro domain and a variable highly phosphorylated c-terminal domain. nsp3 forms complexes with cellular proteins, but its role in virus replication is poorly understood and protein interaction domains have not been defined. as the n-terminal macro domain can bind poly(adp-ribose) (par), and par polymerase-1 (parp-1) is activated and autoribosylated during sindbis virus (sinv) infection, it was hypothesized that parp-1 and ... | 2009 | 19515826 |
| lineage 2 west nile virus as cause of fatal neurologic disease in horses, south africa. | serologic evidence suggests that west nile virus (wnv) is widely distributed in horses in southern africa. however, because few neurologic cases have been reported, endemic lineage 2 strains were postulated to be nonpathogenic in horses. recent evidence suggests that highly neuroinvasive lineage 2 strains exist in humans and mice. to determine whether neurologic cases are being missed in south africa, we tested 80 serum or brain specimens from horses with unexplained fever (n = 48) and/or neurol ... | 2009 | 19523285 |
| safety and immunogenicity of boosting bcg vaccinated subjects with bcg: comparison with boosting with a new tb vaccine, mva85a. | to investigate the safety and immunogenicity of a booster bcg vaccination delivered intradermally in healthy, bcg vaccinated subjects and to compare with a previous clinical trial where bcg vaccinated subjects were boosted with a new tb vaccine, mva85a. | 2009 | 19529780 |
| serological examination of songbirds (passeriformes) for mosquito-borne viruses sindbis, tahyna, and batai in a south moravian wetland (czech republic). | a total of 178 free-living birds of 14 species of 7 families of passeriformes sampled in a freshwater reedswamp habitat in southern moravia in july 2006 were examined for hemagglutination-inhibiting (hi) antibodies to alphavirus sindbis (sinv), and bunyaviruses tahyna (tahv) and batai (batv). hemagglutination-inhibiting antibody was detected against all three viruses, but at different frequencies: sinv 0.7%, tahv 14.0%, and batv 6.8%. the survey indicates circulation of mosquito-borne viruses ta ... | 2009 | 19534626 |
| a high capacity alphavirus heterologous gene delivery system. | a novel replication competent sindbis virus based gene delivery vector has been developed for the introduction of genetic cargo into cell lines in vitro and potentially, animal models in vivo. this delivery system expands the previous uses of sindbis virus as a gene delivery system in that no replicons are required and the resulting cargo containing virus particles are infectious. the heterologous vector is based on a morphological mutant in c, ser180/gly183 which produces larger than the normal ... | 2009 | 19535122 |
| regulation of synaptic structure by ubiquitin c-terminal hydrolase l1. | ubiquitin c-terminal hydrolase l1 (uch-l1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. here, we show that uch-l1 functions in maintaining normal synaptic structure in hippocampal neurons. we found that uch-l1 activity is rapidly upregulated by nmda receptor activation, which leads to an increase in the levels of free monomeric ubiquitin. conversely, pharmacological inhibition of uch-l1 signific ... | 2009 | 19535597 |
| origins of alphavirus-derived small rnas in mosquitoes. | the continual transmission in nature of many arthropod-borne viruses depends on the establishment of a persistent, nonpathogenic infection in a mosquito vector. the importance of antiviral immunity directed by small rnas in the mechanism by which alphaviruses establish a persistent, nonpathogenic infection in the mosquito vector has recently been demonstrated. the origin of the small rnas central to this rna silencing response has recently been the subject of debate. here we briefly summarize wh ... | 2009 | 19535909 |
| sindbis virus replicon-based dna vaccine encoding rabies virus glycoprotein elicits specific humoral and cellular immune response in dogs. | a sindbis virus (sinv) replicon-based dna vaccine encoding rabies virus (rabv) glycoprotein g developed previously (saxena et al., vaccine 26, 6592, 2008) was used for immunization of dogs against rabies. the intradermal injection of dna vaccine into external ear generated protective level of virus neutralizing antibodies. the cellular immune response was specific to rabv, in particular by an increase in cd3+cd4+ and cd3+cd8+ lymphocytes. this study has demonstrated that the sinv replicon-based ... | 2009 | 19537908 |
| deficiency of a potential 3p21.3 tumor suppressor gene ube1l (uba7) does not accelerate lung cancer development in k-rasla2 mice. | genetic lesions in chromosomal region 3p21.3 marks one of the earliest events in human lung cancer development. it is hypothesized that one or more tumor suppressor genes reside in this region. identification and characterization of these genes are important for the understanding of lung cancer initiation. ube1l (uba7) is a long-suspected 3p21.3 residing tumor suppressor gene. it encodes the key enzyme that activates isgylation, a novel, ubiquitination-like, post-translational protein modificati ... | 2009 | 18571763 |
| controlled propagation of replication-competent sindbis viral vector using suicide gene strategy. | a major concern of using viral gene therapy is the potential for uncontrolled vector propagation and infection that might result in serious deleterious effects. to enhance the safety, several viral vectors, including vectors based on sindbis virus, were engineered to lose their capability to replicate and spread after transduction of target cells. such designs, however, could dramatically reduce the therapeutic potency of the viral vectors, resulting in the need for multiple dosages to achieve t ... | 2009 | 18818670 |
| role of thiol/disulfide exchange in newcastle disease virus entry. | newcastle disease virus (ndv) entry into host cells is mediated by the hemagglutinin-neuraminidase (hn) and fusion (f) glycoproteins. we previously showed that production of free thiols in f protein is required for membrane fusion directed by f protein (s. jain et al., j. virol. 81:2328-2339, 2007). in the present study we evaluated the oxidation state of f protein in virions and virus-like particles and its relationship to activation of f protein by hn protein, f protein conformational intermed ... | 2009 | 18922867 |