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repair and polyadenylation of a naturally occurring hepatitis c virus 3' nontranslated region-shorter variant in selectable replicon cell lines.the 3' nontranslated region (ntr) of the hepatitis c virus (hcv) genome is highly conserved and contains specific cis-acting rna motifs that are essential in directing the viral replication machinery to initiate at the correct 3' end of the viral genome. since the ends of viral genomes may be damaged by cellular rnases, preventing the initiation of viral rna replication, stable rna hairpin structures in the 3' ntr may also be essential in host defense against exoribonucleases. during 3'-terminal ...200616611892
mutations in the endodomain of sindbis virus glycoprotein e2 define sequences critical for virus assembly.envelopment of sindbis virus at the plasma membrane is a multistep process in which an initial step is the association of the e2 protein via a cytoplasmic endodomain with the preassembled nucleocapsid. sindbis virus is vectored in nature by blood-sucking insects and grows efficiently in a number of avian and mammalian vertebrate hosts. the assembly of sindbis virus, therefore, must occur in two very different host cell environments. mammalian cells contain cholesterol which insect membranes lack ...200616611906
neonatal immunization with a sindbis virus-dna measles vaccine induces adult-like neutralizing antibodies and cell-mediated immunity in the presence of maternal antibodies.infants younger than age 9 mo do not respond reliably to the live attenuated measles vaccine due the immaturity of their immune system and the presence of maternal abs that interfere with successful immunization. we evaluated the immune responses elicited by sindbis virus replicon-based dna vaccines encoding measles virus (mv) hemagglutinin (h, pmsin-h) or both hemagglutinin and fusion (f, pmsinh-fdu) glycoproteins in neonatal mice born to naive and measles-immune mothers. despite the presence o ...200616622037
partial reconstitution of the cd4+-t-cell compartment in cd4 gene knockout mice restores responses to tuberculosis dna vaccines.reactivation tuberculosis (tb) is a serious problem in immunocompromised individuals, especially those with human immunodeficiency virus (hiv) coinfection. the adaptive immune response mediated by cd4+ and cd8+ t cells is known to confer protection against tb. hence, vaccines against tb are designed to activate these two components of the immune system. anti-tb dna vaccines encoding the immunodominant proteins ag85a, ag85b, and psts-3 from mycobacterium tuberculosis are ineffective in mice lacki ...200616622212
[detection of banna virus-specific nucleic acid with taqman rt-pcr assay].to develop a rapid and more sensitive taqman rt-pcr assay specific for banna virus.200616642219
sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity.alphavirus vectors have emerged as a promising strategy for the development of cancer vaccines and gene therapy applications. in this study, we used the replication-defective vaccine vector sin replicon particles from a new packaging cell line (pcl) to develop sin replicon particles encoding calreticulin (crt) linked to a model tumor antigen, human papillomavirus type 16 (hpv16) e7 protein. the linkage of crt to e7 in sin replicon particles resulted in a significant increase in e7-specific cd8(+ ...200616645621
bioportfolio: lifelong persistence of variant and prototypic erythrovirus dna genomes in human tissue.human erythrovirus is a minute, single-stranded dna virus causing many diseases, including erythema infectiosum, arthropathy, and fetal death. after primary infection, the viral genomes persist in solid tissues. besides the prototype, virus type 1, two major variants (virus types 2 and 3) have been identified recently, the clinical significance and epidemiology of which are mostly unknown. we examined 523 samples of skin, synovium, tonsil, or liver (birth year range, 1913-2000), and 1,640 sera, ...200616651522
induction of apoptosis limits cytomegalovirus cross-species infection.cross-species infections are responsible for the majority of emerging and re-emerging viral diseases. however, little is known about the mechanisms that restrict viruses to a certain host species, and the factors viruses need to cross the species barrier and replicate in a different host. cytomegaloviruses (cmvs) are representatives of the beta-herpesviruses that are highly species specific. they replicate only in cells of their own or a closely related species. in this study, the molecular mech ...200616688216
altered immune response to cns viral infection in mice with a conditional knock-down of macrophage-lineage cells.neuroadapted sindbis virus (nsv) is a neuronotropic virus that causes hindlimb paralysis in susceptible mice and rats. the authors and others have demonstrated that though death of infected motor neurons occurs, bystander death of uninfected neurons also occurs and both contribute to the paralysis that ensues following infection. the authors have previously shown that the treatment of nsv-infected mice with minocycline, an inhibitor that has many functions within the central nervous system (cns) ...200616691560
gamma interferon plays a crucial early antiviral role in protection against west nile virus infection.west nile virus (wnv) causes a severe central nervous system (cns) infection in humans, primarily in the elderly and immunocompromised. prior studies have established an essential protective role of several innate immune response elements, including alpha/beta interferon (ifn-alpha/beta), immunoglobulin m, gammadelta t cells, and complement against wnv infection. in this study, we demonstrate that a lack of ifn-gamma production or signaling results in increased vulnerability to lethal wnv infect ...200616699014
molecular determinants of substrate specificity for semliki forest virus nonstructural protease.the c-terminal cysteine protease domain of semliki forest virus nonstructural protein 2 (nsp2) regulates the virus life cycle by sequentially cleaving at three specific sites within the virus-encoded replicase polyprotein p1234. the site between nsp3 and nsp4 (the 3/4 site) is cleaved most efficiently. analysis of semliki forest virus-specific cleavage sites with shuffled n-terminal and c-terminal half-sites showed that the main determinants of cleavage efficiency are located in the region prece ...200616699022
a herpes simplex virus recombinant that exhibits a single-chain antibody to her2/neu enters cells through the mammary tumor receptor, independently of the gd receptors.the human epidermal growth factor receptor 2/neuregulin (her2/neu) receptor is overexpressed in highly malignant mammary and ovarian tumors and correlates with a poor prognosis. it is a target for therapy; humanized monoclonal antibodies to her2 have led to increased survival of patients with her2/neu-positive breast cancer. as a first step in the design of an oncolytic herpes simplex virus able to selectively infect her2/neu-positive cells, we constructed two recombinants, r-lm11 and r-lm11l, t ...200616699034
genome microevolution of chikungunya viruses causing the indian ocean outbreak.a chikungunya virus outbreak of unprecedented magnitude is currently ongoing in indian ocean territories. in réunion island, this alphavirus has already infected about one-third of the human population. the main clinical symptom of the disease is a painful and invalidating poly-arthralgia. besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed severe clinical signs, i.e., neurological signs or fulminant hepatitis.200616700631
phosphatidylserine is involved in gene expression from sindbis virus subgenomic promoter.sindbis virus replication is mediated by an rna replicase translated from viral rna genome. the replicase synthesizes progeny genomic rna and shorter rna (subgenomic rna) carrying viral structural genes in association with cytoplasmic membranes. here we examined the involvement of a membrane lipid, phosphatidylserine (ps), in sindbis virus gene expression using chinese hamster ovary cell mutants. when the mutant cells were transfected with viral replicon rna, in which the structural genes downst ...200616701551
potential arbovirus emergence and implications for the united kingdom.arboviruses have evolved a number of strategies to survive environmental challenges. this review examines the factors that may determine arbovirus emergence, provides examples of arboviruses that have emerged into new habitats, reviews the arbovirus situation in western europe in detail, discusses potential arthropod vectors, and attempts to predict the risk for arbovirus emergence in the united kingdom. we conclude that climate change is probably the most important requirement for the emergence ...200616704800
postsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber-purkinje cell synapses via bdnf.the maintenance of synaptic functions is essential for neuronal information processing, but cellular mechanisms that maintain synapses in the adult brain are not well understood. here, we report an activity-dependent maintenance mechanism of parallel fiber (pf)-purkinje cell (pc) synapses in the cerebellum. when postsynaptic metabotropic glutamate receptor (mglur) or inositol 1,4,5-trisphosphate (ip(3)) signaling was chronically inhibited in vivo, pf-pc synaptic strength decreased because of a d ...200616709674
ubp43 is a novel regulator of interferon signaling independent of its isg15 isopeptidase activity.interferons (ifns) regulate diverse cellular functions through activation of the janus kinase-signal transducer and activator of transcription (jak-stat) pathway. lack of ubp43, an ifn-inducible isg15 deconjugating enzyme, leads to ifn hypersensitivity in ubp43-/- mice, suggesting an important function of ubp43 in downregulation of ifn responses. here, we show that ubp43 negatively regulates ifn signaling independent of its isopeptidase activity towards isg15. ubp43 functions specifically for ty ...200616710296
production and characterization of vaccines based on flaviviruses defective in replication.to develop new vaccine candidates for flavivirus infections, we have engineered two flaviviruses, yellow fever virus (yfv) and west nile virus (wnv), that are deficient in replication. these defective pseudoinfectious viruses (pivs) lack a functional copy of the capsid (c) gene in their genomes and are incapable of causing spreading infection upon infection of cells both in vivo and in vitro. however, they produce extracellular e protein in form of secreted subviral particles (svps) that are kno ...200616712897
partial beclin 1 silencing aggravates doxorubicin- and fas-induced apoptosis in hepg2 cells.to investigate the role of beclin 1 on the susceptibility of hepg2 cells to undergo apoptosis after anti-fas antibody or doxorubicin treatment.200616718815
type i interferons are essential for the efficacy of replicase-based dna vaccines.the immunogenicity and efficacy of nucleic acid vaccines can be greatly enhanced when antigen production is under the control of an alphaviral replicase enzyme. however, replicase-mediated mrna overproduction does not necessarily result in enhanced antigen level. instead, the strong adaptive immune response of alphavirus replicon-based vectors is due to their production of double-stranded rna (dsrna) intermediates, which trigger innate immunity. because viral infections are known to trigger inna ...200616725231
sindbis virus nonstructural protein nsp2 is cytotoxic and inhibits cellular transcription.replication of alphaviruses in vertebrate cells strongly affects cell physiology and ultimately leads to development of a cytopathic effect (cpe) and cell death. sindbis virus (sin) replication causes major changes in cellular macromolecular synthesis, in which the strong downregulation of transcription of cellular mrnas and rrnas plays a critical role. sin nonstructural protein nsp2 was previously proposed as one of the main regulators of virus-host cell interactions, because point mutations in ...200616731907
blocking of interferon-induced jak-stat signaling by japanese encephalitis virus ns5 through a protein tyrosine phosphatase-mediated mechanism.japanese encephalitis virus (jev), a mosquito-borne flavivirus that causes severe human disease, has been shown to block the interferon (ifn)-induced janus kinase signal transducer and activation of transcription (jak-stat) signaling cascade by preventing tyk2 tyrosine phosphorylation and stat activation. in this study, we demonstrate that expression of the jev nonstructural protein ns5 readily blocked ifn-stimulated jak-stat signaling events such as stat1 nuclear translocation and tyrosine phos ...200616731929
polyadenylation of genomic rna and initiation of antigenomic rna in a positive-strand rna virus are controlled by the same cis-element.genomes and antigenomes of many positive-strand rna viruses contain 3'-poly(a) and 5'-poly(u) tracts, respectively, serving as mutual templates. mechanism(s) controlling the length of these homopolymeric stretches are not well understood. here, we show that in coxsackievirus b3 (cvb3) and three other enteroviruses the poly(a) tract is approximately 80-90 and the poly(u) tract is approximately 20 nt-long. mutagenesis analysis indicate that the length of the cvb3 3'-poly(a) is determined by the or ...200616738134
tau aggregation and progressive neuronal degeneration in the absence of changes in spine density and morphology after targeted expression of alzheimer's disease-relevant tau constructs in organotypic hippocampal slices.alzheimer's disease (ad) is characterized by progressive loss of neurons in selected brain regions, extracellular accumulations of amyloid beta, and intracellular fibrils containing hyperphosphorylated tau. tau mutations in familial tauopathies confirmed a central role of tau pathology; however, the role of tau alteration and the sequence of tau-dependent neurodegeneration in ad remain elusive. using sindbis virus-mediated expression of ad-relevant tau constructs in hippocampal slices, we show t ...200616738255
relationships between host viremia and vector susceptibility for arboviruses.using a threshold model where a minimum level of host viremia is necessary to infect vectors affects our assessment of the relative importance of different host species in the transmission and spread of these pathogens. other models may be more accurate descriptions of the relationship between host viremia and vector infection. under the threshold model, the intensity and duration of the viremia above the threshold level is critical in determining the potential numbers of infected mosquitoes. a ...016739425
regulation of inducible nitric oxide synthase gene in glial cells.elevated levels of no produced within the central nervous system (cns) are associated with the pathogenesis of neuroinflammatory and neurodegenerative human diseases such as multiple sclerosis, hiv dementia, brain ischemia, trauma, parkinson's disease, and alzheimer's disease. resident glial cells in the cns (astroglia and microglia) express inducible nitric oxide synthase (inos) and produce high levels of no in response to a wide variety of proinflammatory and degenerative stimuli. although pat ...200616771683
suppression of the interferon-mediated innate immune response by pseudorabies virus.pseudorabies virus (prv) is an alphaherpesvirus related to the human pathogens herpes simplex virus type 1 (hsv-1) and varicella-zoster virus. prv is capable of infecting and killing a wide variety of mammals. how it avoids innate immune defenses in so many hosts is not understood. while the anti-interferon (ifn) strategies of hsv-1 have been studied, little is known about how prv evades the ifn-mediated immune response. in this study, we determined if wild-type prv infection can overcome the es ...200616775323
x-ray structures of the n- and c-terminal domains of a coronavirus nucleocapsid protein: implications for nucleocapsid formation.coronaviruses cause a variety of respiratory and enteric diseases in animals and humans including severe acute respiratory syndrome. in these enveloped viruses, the filamentous nucleocapsid is formed by the association of nucleocapsid (n) protein with single-stranded viral rna. the n protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signaling pathways. we describe the structure of the two proteolytically resistant domains of the n p ...200616775348
morphology of bhk-21 cells infected with sindbis virus temperature-sensitive mutants in complementation groups d and e.bhk-21 cells infected with temperature-sensitive mutants of sindbis virus in complementation groups d and e differed in their appearance under nonpermissive conditions. cells infected at nonpermissive temperature with virus defective in complementation group e had nucleocapsids attached in large numbers to the inside surface of the host plasma membrane. infection with a group d mutant produced nucleocapsids that did not attach to the plasma membrane but rather remained free in the cell cytoplasm ...197516789157
novel putative targets of n-ethylmaleimide sensitive fusion protein (nsf) and alpha/beta soluble nsf attachment proteins (snaps) include the pak-binding nucleotide exchange factor betapix.n-ethylmaleimide sensitive fusion protein (nsf) is a chaperone that plays a crucial role in the fusion of vesicles with target membranes. nsf mediates the atp-consuming dissociation of a core protein complex that assembles during vesicle fusion and it thereby recharges the fusion machinery to perform multiple rounds of fusion. the binding of nsf to the core complex is mediated by co-chaperones named soluble nsf attachment proteins (snaps), for which three isoforms (alpha, beta and gamma) are kno ...200616795052
hepatitis c virus entry depends on clathrin-mediated endocytosis.due to difficulties in cell culture propagation, the mechanisms of hepatitis c virus (hcv) entry are poorly understood. here, postbinding cellular mechanisms of hcv entry were studied using both retroviral particles pseudotyped with hcv envelope glycoproteins (hcvpp) and the hcv clone jfh-1 propagated in cell culture (hcvcc). hcvpp entry was measured by quantitative real-time pcr after 3 h of contact with target cells, and hcvcc infection was quantified by immunoblot analysis and immunofluoresce ...200616809302
pkr and rnase l contribute to protection against lethal west nile virus infection by controlling early viral spread in the periphery and replication in neurons.west nile virus (wnv) is a neurotropic, mosquito-borne flavivirus that can cause lethal meningoencephalitis. type i interferon (ifn) plays a critical role in controlling wnv replication, spread, and tropism. in this study, we begin to examine the effector mechanisms by which type i ifn inhibits wnv infection. mice lacking both the interferon-induced, double-stranded-rna-activated protein kinase (pkr) and the endoribonuclease of the 2',5'-oligoadenylate synthetase-rnase l system (pkr(-/-) x rl(-/ ...200616809306
prime-boost immunization using dna vaccine and recombinant orf virus protects pigs against pseudorabies virus (herpes suid 1).the present study demonstrates the protective potential of a novel prime-boost vaccination strategy of pigs against lethal pseudorabies virus (prv; herpes suid 1) infection. animals were primed with sindbis virus-derived plasmids that express viral glycoproteins gc and gd (gc- and gd-psin) and subsequently booster immunized with orf virus (orfv; parapoxvirus) recombinants expressing gc and gd (d1701-vrvgc and -vrvgd). the prime-boost vaccination induced strong humoral and cellular-like prv-speci ...200616814432
tumor-specific in vivo transfection with hsv-1 thymidine kinase gene using a sindbis viral vector as a basis for prodrug ganciclovir activation and pet.one type of gene therapy of tumors, gene-directed enzyme-prodrug therapy (gdept), holds considerable promise, although practical considerations limit its clinical applicability. these include the lack of acceptable noninvasive methods that are adaptable to humans for selective tumor targeting of the therapeutic genetic material. sindbis virus is an oncolytic, alpha-virus that selectively targets tumors through the 67-kda laminin receptor (lamr). in this report we describe a novel approach that p ...200616818948
maintenance of cd8 effector t cells by cd4 helper t cells eradicates growing tumors and promotes long-term tumor immunity.human papillomavirus, particularly type 16 (hpv-16), is present in more than 99% of cervical cancers, and oncogenic hpv infection is one of the most important etiologies. it is now clear that cd4(+) t cells play an important role in controlling hpv-associated lesions because immunocompromised patients have a higher frequency of hpv-associated lesions. in the current study, we characterized the significance of cd4(+) t cells in the generation of e7-specific cd8(+) t cell immune responses in mice ...200616824651
cubic phases in phosphatidylcholine-cholesterol mixtures: cholesterol as membrane "fusogen".x-ray diffraction reveals that mixtures of some unsaturated phosphatidylcholines (pcs) with cholesterol (chol) readily form inverted bicontinuous cubic phases that are stable under physiological conditions. this effect was studied in most detail for dioleoyl pc/chol mixtures with molar ratios of 1:1 and 3:7. facile formation of im3m and pn3m phases with lattice constants of 30-50 nm and 25-30 nm, respectively, took place in phosphate-buffered saline, in sucrose solution, and in water near the te ...200616829556
epitope-blocking enzyme-linked immunosorbent assay for detection of antibodies to ross river virus in vertebrate sera.we describe the development of an epitope-blocking enzyme-linked immunosorbent assay (elisa) for the sensitive and rapid detection of antibodies to ross river virus (rrv) in human sera and known vertebrate host species. this elisa provides an alternative method for the serodiagnosis of rrv infections.200616829622
carrageenan is a potent inhibitor of papillomavirus infection.certain sexually transmitted human papillomavirus (hpv) types are causally associated with the development of cervical cancer. our recent development of high-titer hpv pseudoviruses has made it possible to perform high-throughput in vitro screens to identify hpv infection inhibitors. comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted hpvs. ...200616839203
entry of feline calicivirus is dependent on clathrin-mediated endocytosis and acidification in endosomes.feline calicivirus is a major causative agent of respiratory disease in cats. it is also one of the few cultivatable members of caliciviridae. we have examined the entry process of feline calicivirus (fcv). an earlier study demonstrated that acidification in endosomes may be required. we have confirmed this observation and expanded upon it, demonstrating, using drugs to inhibit the various endocytic pathways and dominant-negative mutants, that fcv infects cells via clathrin-mediated endocytosis. ...200616840330
newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death.newcastle disease virus (ndv), an avian paramyxovirus, is tumor selective and intrinsically oncolytic. here, we present evidence that genetically modified, recombinant ndv strains are cytotoxic to human tumor cell lines of ecto-, endo-, and mesodermal origin. we show that cytotoxicity against tumor cells is due to multiple caspase-dependent pathways of apoptosis independent of interferon signaling competence. the signaling pathways of ndv-induced, cancer cell-selective apoptosis are not well und ...200616840332
ribosomal protein s6 associates with alphavirus nonstructural protein 2 and mediates expression from alphavirus messages.although alphaviruses dramatically alter cellular function within hours of infection, interactions between alphaviruses and specific host cellular proteins are poorly understood. although the alphavirus nonstructural protein 2 (nsp2) is an essential component of the viral replication complex, it also has critical auxiliary functions that determine the outcome of infection in the host. to gain a better understanding of nsp2 function, we sought to identify cellular proteins with which venezuelan e ...200616840351
utilization of host sr protein kinases and rna-splicing machinery during viral replication.although the viral genome is often quite small, it encodes a broad series of proteins. the virus takes advantage of the host-rna-processing machinery to provide the alternative splicing capability necessary for the expression of this proteomic diversity. serine-arginine-rich (sr) proteins and the kinases that activate them are central to this alternative splicing machinery. in studies reported here, we use the hiv genome as a model. we show that hiv expression decreases overall sr protein/activi ...200616840555
bats: important reservoir hosts of emerging viruses.bats (order chiroptera, suborders megachiroptera ["flying foxes"] and microchiroptera) are abundant, diverse, and geographically widespread. these mammals provide us with resources, but their importance is minimized and many of their populations and species are at risk, even threatened or endangered. some of their characteristics (food choices, colonial or solitary nature, population structure, ability to fly, seasonal migration and daily movement patterns, torpor and hibernation, life span, roo ...200616847084
cryptosporidium parvum infects human cholangiocytes via sphingolipid-enriched membrane microdomains.cryptosporidium parvum attaches to intestinal and biliary epithelial cells via specific molecules on host-cell surface membranes including gal/galnac-associated glycoproteins. subsequent cellular entry of this parasite depends on host-cell membrane alterations to form a parasitophorous vacuole via activation of phosphatidylinositol 3-kinase (pi-3k)/cdc42-associated actin remodelling. how c. parvum hijacks these host-cell processes to facilitate its infection of target epithelia is unclear. using ...200616848787
sindbis virus infection of two model insect cell systems--a comparative study.sindbis, the prototype of the alphaviruses causes mosquito-borne diseases in mammals and replicates in a wide variety of vertebrate and invertebrate cell cultures. this characteristic can be exploited to use the vast array of drosophila genetic information available for investigations of the interaction of sindbis virus with an alternate invertebrate host. for this purpose, a comparative study of sindbis virus infection of schnieder-2 drosophila (s2) cells to cells of the mosquito aedes albopict ...200616854488
a 5' rna element promotes dengue virus rna synthesis on a circular genome.the mechanisms of rna replication of plus-strand rna viruses are still unclear. here, we identified the first promoter element for rna synthesis described in a flavivirus. using dengue virus as a model, we found that the viral rdrp discriminates the viral rna by specific recognition of a 5' element named sla. we demonstrated that rna-rna interactions between 5' and 3' end sequences of the viral genome enhance dengue virus rna synthesis only in the presence of an intact sla. we propose a novel me ...200616882970
hiv and cxcr4 in a kiss of autophagic death.aids is characterized by cd4+ t lymphocyte depletion, yet the mechanisms underlying this central aspect of hiv pathogenesis are still poorly understood. in this issue of the jci, espert et al. identify a mechanism by which the hiv envelope glycoprotein can induce death in uninfected cd4+ t cells (see the related article beginning on page 2161). the hiv envelope glycoprotein interacts with cxc chemokine receptor 4 to activate the lysosomal degradation pathway of autophagy, which is necessary for ...200616886053
autophagy is involved in t cell death after binding of hiv-1 envelope proteins to cxcr4.hiv-1 envelope glycoproteins (env), expressed at the cell surface, induce apoptosis of uninfected cd4+ t cells, contributing to the development of aids. here we demonstrate that, independently of hiv replication, transfected or hiv-infected cells that express env induced autophagy and accumulation of beclin 1 in uninfected cd4+ t lymphocytes via cxcr4. the same phenomena occurred in a t cell line and in transfected hek.293 cells that expressed both wild-type cxcr4 and a truncated form of cd4 tha ...200616886061
possible ecology and epidemiology of medically important mosquito-borne arboviruses in great britain.nine different arboviruses are known to be transmitted by, or associated with, mosquitoes in europe, and several (west nile, sindbis and tahyna viruses) are reported to cause outbreaks of human disease. although there have been no reported human cases in great britain (gb), there have been no published in-depth serological surveys for evidence of human infection. this paper investigates the ecological and entomological factors that could influence or restrict transmission of these viruses in gb, ...200716893487
tracking and elucidating alphavirus-host protein interactions.viral infections cause profound alterations in host cells. here, we explore the interactions between proteins of the alphavirus sindbis and host factors during the course of mammalian cell infection. using a mutant virus expressing the viral nsp3 protein tagged with green fluorescent protein (gfp) we directly observed nsp3 localization and isolated nsp3-interacting proteins at various times after infection. these results revealed that host factor recruitment to nsp3-containing complexes was time ...200616895903
actin-associated neurabin-protein phosphatase-1 complex regulates hippocampal plasticity.protein phosphatase-1 (pp1) has been implicated in the control of long-term potentiation (ltp) and depression (ltd) in rat hippocampal ca1 neurons. pp1 catalytic subunits associate with multiple postsynaptic regulatory subunits, but the pp1 complexes that control hippocampal ltp and ltd in the rat hippocampus remain unidentified. the neuron-specific actin-binding protein, neurabin-i, is enriched in dendritic spines, and tethers pp1 to actin-rich postsynaptic density to regulate morphology and ma ...200616899074
transient low ph treatment enhances infection of lentiviral vector pseudotypes with a targeting sindbis envelope.efficient transduction of primary hematopoietic cell types by oncoretroviral vectors and lentiviral vectors with a variety of different envelope pseudotypes has proven to be difficult. we recently developed a lentiviral vector based upon a modified sindbis virus envelope that allows targeted transduction via antibody recognition to specific cells in unfractionated cell populations. however, similar to other envelope pseudotypes, the utility of this vector for some primary hematopoietic cells was ...200616905172
structure determination of clathrin coats to subnanometer resolution by single particle cryo-electron microscopy.clathrin triskelions can assemble into lattices of different shapes, sizes and symmetries. for many years, the structures of clathrin lattices have been studied by single particle cryo-electron microscopy, which probed the architecture of the d6 hexagonal barrel clathrin coat at the molecular level. by introducing additional image processing steps we have recently produced a density map for the d6 barrel clathrin coat at subnanometer resolution, enabling us to generate an atomic model for this l ...200616908193
structural and functional basis for adp-ribose and poly(adp-ribose) binding by viral macro domains.macro domains constitute a protein module family found associated with specific histones and proteins involved in chromatin metabolism. in addition, a small number of animal rna viruses, such as corona- and toroviruses, alphaviruses, and hepatitis e virus, encode macro domains for which, however, structural and functional information is extremely limited. here, we characterized the macro domains from hepatitis e virus, semliki forest virus, and severe acute respiratory syndrome coronavirus (sars ...200616912299
rapid adaptation of a recombinant vesicular stomatitis virus to a targeted cell line.vesicular stomatitis virus (vsv) is being developed for cancer therapy. we created a recombinant replicating vsv (rrvsv) that preferentially infected her2/neu-expressing breast cancer cells. this rrvsv did not express the native vsv-g glycoprotein (gp). instead, it expressed a chimeric sindbis gp which included a single-chain antibody (sca) directed to the human her2/neu receptor. the virus infected mouse mammary carcinoma cells (d2f2/e2) expressing her2/neu 23-fold better than the parent cells ...200616912309
role of the low-density lipoprotein receptor in entry of bovine viral diarrhea virus.among several proposed cellular receptors for bovine viral diarrhea virus (bvdv), the low-density lipoprotein (ldl) receptor is of special interest because it is also considered a receptor for the related hepatitis c virus. it has been reported that an anti-ldl receptor monoclonal antibody blocked the infection of bovine cells by bvdv and that the resistance of bovine crib cells (cells resistant to infection with bvdv) (e. f. flores and r. o. donis, virology 208:565-575, 1995) to bvdv infection ...200616928760
rotavirus activates jnk and p38 signaling pathways in intestinal cells, leading to ap-1-driven transcriptional responses and enhanced virus replication.rotavirus infection is known to regulate transcriptional changes in many cellular genes. the transcription factors nf-kappab and ap-1 are activated by rotavirus infection, but the upstream processes leading to these events are largely unidentified. we therefore studied the activation state during rotavirus infection of c-jun nh2-terminal kinase (jnk) and p38, which are kinases known to activate ap-1. as assessed by western blotting using phospho-specific antibodies, infection with rhesus rotavir ...200616928761
phylogenetic analysis of buggy creek virus: evidence for multiple clades in the western great plains, united states of america.we present the first detailed phylogenetic analysis of buggy creek virus (bcrv), a poorly known alphavirus with transmission cycles involving a cimicid swallow bug (oeciacus vicarius) vector and cliff swallows (petrochelidon pyrrhonota) and house sparrows (passer domesticus) as the principal avian hosts. nucleotide sequences of a 2,075-bp viral envelope glycoprotein-coding region, covering the entire pe2 gene, were determined for 33 bcrv isolates taken from swallow bugs at cliff swallow colonies ...200616936062
c-e1 fusion protein synthesized by rubella virus di rnas maintained during serial passage.rubella virus (rub) replicons are derivatives of the rub infectious cdna clone that retain the nonstructural open reading frame (ns-orf) that encodes the replicase proteins but not the structural protein orf (sp-orf) that encodes the virion proteins. rub defective interfering (di) rnas contain deletions within the sp-orf and thus resemble replicons. di rnas often retain the 5' end of the capsid protein (c) gene that has been shown to modulate virus-specific rna synthesis. however, when replicons ...200616938325
alphavirus capsid protein helix i controls a checkpoint in nucleocapsid core assembly.the assembly of the alphavirus nucleocapsid core has been investigated using an in vitro assembly system. the c-terminal two-thirds of capsid protein (cp), residues 81 to 264 in sindbis virus (sinv), have been previously shown to have all the rna-cp and cp-cp contacts required for core assembly in vitro. helix i, which is located in the n-terminal dispensable region of the cp, has been proposed to stabilize the core by forming a coiled coil in the cp dimer formed by the interaction of residues 8 ...200616940497
altered central nervous system gene expression caused by congenitally acquired persistent infection with lymphocytic choriomeningitis virus.neonatal infection of most mouse strains with lymphocytic choriomeningitis virus (lcmv) leads to a life-long persistent infection characterized by high virus loads in the central nervous system (cns) in the absence of inflammation and tissue destruction. these mice, however, exhibit impaired learning and memory. the occurrence of cognitive defects in the absence of overt cns pathology led us to the hypothesis that chronic virus infection may contribute to neuronal dysfunction by altering the hos ...200616940520
modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein.perturbation of the function of endoplasmic reticulum (er) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (upr). severe acute respiratory syndrome (sars) coronavirus (sars-cov) uses er as a site for synthesis and processing of viral proteins. in this report, we demonstrate that infection with sars-cov induces the upr in cultured cells. a comparison with m, e, and nsp6 proteins indicates that sars-cov spike (s) protein sufficiently induce ...200616940539
acid sphingomyelinase deficiency increases susceptibility to fatal alphavirus encephalomyelitis.sindbis virus (sv), an enveloped virus with a single-stranded, plus-sense rna genome, is the prototype alphavirus in the togaviridae family. in mice, sv infects neurons and can cause apoptosis of immature neurons. sphingomyelin (sm) is the most prevalent cellular sphingolipid, is particularly abundant in the nervous systems of mammals, and is required for alphavirus fusion and entry. the level of sm is tightly regulated by sphingomyelinases. a defect in acid sphingomyelinase (asmase) results in ...200616943298
the effects of n-terminal insertion into vsv-g of an scfv peptide.recombinant retroviruses, including lentiviruses, are the most widely used vectors for both in vitro and in vivo stable gene transfer. however, the inability to selectively deliver transgenes into cells of interest limits the use of this technology. due to its wide tropism, stability and ability to pseudotype a range of viral vectors, vesicular stomatitis virus g protein (vsv-g) is the most commonly used pseudotyping protein. here, we attempted to engineer this protein for targeting purposes. ch ...200616948856
immunization with a low-dose replicon dna vaccine encoding phl p 5 effectively prevents allergic sensitization.replicase-based dna vaccines stimulate t(h)1-biased immune responses at ultralow doses and induce self-removal of transfected cells through apoptosis. both aspects are important requirements for efficient and safe dna-based immunotherapy of type i allergies.200616950295
detection of seroconversion to west nile virus, usutu virus and sindbis virus in uk sentinel chickens.we previously reported evidence of west nile virus (wnv) circulation in uk birds, probably introduced by migratory birds from overseas. we now demonstrate wnv-specific seroconversion in sentinel chickens raised on an english farm. maternal neutralizing antibodies to wnv in hatchlings declined within three weeks. during the following months, healthy chickens developed wnv neutralizing antibodies that were confirmed by immunoblotting and indirect immunofluorescence tests using wnv antigens. the pr ...200616952307
recombination and selection in the evolution of picornaviruses and other mammalian positive-stranded rna viruses.picornaviridae are a large virus family causing widespread, often pathogenic infections in humans and other mammals. picornaviruses are genetically and antigenically highly diverse, with evidence for complex evolutionary histories in which recombination plays a major part. to investigate the nature of recombination and selection processes underlying the evolution of serotypes within different picornavirus genera, large-scale analysis of recombination frequencies and sites, segregation by serotyp ...200616956935
reverse transcription-pcr-enzyme-linked immunosorbent assay for rapid detection and differentiation of alphavirus infections.due to the lack of a rapid, simple, and inexpensive assay for detecting alphavirus infections, we combined a reverse transcription-pcr with an enzyme-linked immunosorbent assay (rt-pcr-elisa) to identify human pathogenic alphaviruses that are endemic in the new world. by combining the sensitivity of pcr, the detection simplicity of elisa, and the specificities of dna probes, this method rapidly detected and differentiated closely related species and subtypes of several medically important alphav ...200616957044
antiviral action of the tumor suppressor arf.oncogenic viruses frequently target the pathways controlled by tumor suppressor genes, suggesting an extra function for these proteins as antiviral factors. the control exerted by the tumor suppressor arf on cellular proliferation is crucial to restrict tumor development; however, a potential contribution of arf to prevent viral infectivity has remained unexplored. in the present study, we investigated the consequences of loss or increased expression of arf on viral infection. our results reveal ...200616957780
venezuelan equine encephalitis virus transmission and effect on pathogenesis.quantifying the dose of an arbovirus transmitted by mosquitoes is essential for designing pathogenesis studies simulating natural infection of vertebrates. titration of saliva collected in vitro from infected mosquitoes may not accurately estimate titers transmitted during blood feeding, and infection by needle injection may affect vertebrate pathogenesis. we compared the amount of venezuelan equine encephalitis virus collected from the saliva of aedes taeniorhynchus to the amount injected into ...200616965696
o'nyong-nyong virus, chad.we report the first laboratory-confirmed human infection with o'nyong-nyong virus in chad. this virus was isolated from peripheral blood mononuclear cells of a patient with evidence of a seroconversion to a virus related to chikungunya virus. genome sequence was partly determined, and phylogenetic studies were conducted.200616965706
oligomerization of hepatitis c virus core protein is crucial for interaction with the cytoplasmic domain of e1 envelope protein.hepatitis c virus (hcv) contains two membrane-associated envelope glycoproteins, e1 and e2, which assemble as a heterodimer in the endoplasmic reticulum (er). in this study, predictive algorithms and genetic analyses of deletion mutants and glycosylation site variants of the e1 glycoprotein were used to suggest that the glycoprotein can adopt two topologies in the er membrane: the conventional type i membrane topology and a polytopic topology in which the protein spans the er membrane twice with ...200616971440
translation of the flavivirus kunjin ns3 gene in cis but not its rna sequence or secondary structure is essential for efficient rna packaging.our previous studies using trans-complementation analysis of kunjin virus (kun) full-length cdna clones harboring in-frame deletions in the ns3 gene demonstrated the inability of these defective complemented rnas to be packaged into virus particles (w. j. liu, p. l. sedlak, n. kondratieva, and a. a. khromykh, j. virol. 76:10766-10775). in this study we aimed to establish whether this requirement for ns3 in rna packaging is determined by the secondary rna structure of the ns3 gene or by the essen ...200616971441
functions of the stem region of the semliki forest virus fusion protein during virus fusion and assembly.membrane fusion of the alphaviruses is mediated by the e1 protein, a class ii virus membrane fusion protein. during fusion, e1 dissociates from its heterodimer interaction with the e2 protein and forms a target membrane-inserted e1 homotrimer. the structure of the homotrimer is that of a trimeric hairpin in which e1 domain iii and the stem region fold back toward the target membrane-inserted fusion peptide loop. the e1 stem region has a strictly conserved length and several highly conserved resi ...200616971447
site-directed antibodies against the stem region reveal low ph-induced conformational changes of the semliki forest virus fusion protein.the e1 envelope protein of the alphavirus semliki forest virus (sfv) is a class ii fusion protein that mediates low ph-triggered membrane fusion during virus infection. like other class i and class ii fusion proteins, during fusion e1 inserts into the target membrane and rearranges to form a trimeric hairpin structure. the postfusion structures of the alphavirus and flavivirus fusion proteins suggest that the "stem" region connecting the fusion protein domain iii to the transmembrane domain inte ...200616973563
the 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9.adeno-associated virus serotype 8 (aav8) is currently emerging as a powerful gene transfer vector, owing to its capability to efficiently transduce many different tissues in vivo. while this is believed to be in part due to its ability to uncoat more readily than other aav serotypes such as aav2, understanding all the processes behind aav8 transduction is important for its application and optimal use in human gene therapy. here, we provide the first report of a cellular receptor for aav8, the 37 ...200616973587
template requirements for recognition and copying by sindbis virus rna-dependent rna polymerase.the sindbis virus (sin) nonstructural protein nsp4 possesses the rna-dependent rna polymerase activity required for the replication of the sin genome and transcription of a subgenomic mrna during infection. isolation of this protein from other viral components of the rna synthetic complex allowed the characterization of template requirements for nsp4-mediated genome replication. the major findings of this study are: (i) in the absence of other viral proteins nsp4 is capable of copying sin plus- ...200716979682
ab initio random model method facilitates 3d reconstruction of icosahedral particles.model-based, three-dimensional (3d) image reconstruction procedures require a starting model to initiate data analysis. we have designed an ab initio method, which we call the random model (rm) method, that automatically generates models to initiate structural analysis of icosahedral viruses imaged by cryo-electron microscopy. the robustness of the rm procedure was demonstrated on experimental sets of images for five representative viruses. the rm method also provides a straightforward way to ge ...200716979906
replicase-based dna vaccines for allergy treatment.replicase-based vaccines were introduced to overcome some of the deficiencies of conventional dna- and rna-based vaccines, including poor efficiency and low stability. at ultra-low doses, these alphavirus-derived vectors elicit cellular as well as humoral immune responses. additionally, replicase-based vectors induce "self-removal" of the vaccine via apoptosis of transfected cells. this chapter describes the construction of a replicon-based dna vaccine vector from commercially available plasmids ...200616988457
cyclophosphamide increases transgene expression mediated by an oncolytic adenovirus in glioma-bearing mice monitored by bioluminescence imaging.approaches to improve the oncolytic potency of replication-competent adenoviruses include the insertion of therapeutic transgenes into the viral genome. little is known about the levels and duration of in vivo transgene expression by cells infected with such "armed" viruses. using a tumor-selective adenovirus encoding firefly luciferase (addelta24cmv-luc) we investigated these questions in an intracranial mouse model for malignant glioma. luciferase expression was detected by bioluminescence ima ...200616996314
in vivo packaging of brome mosaic virus rna3, but not rnas 1 and 2, is dependent on a cis-acting 3' trna-like structure.the four encapsidated rnas of brome mosaic virus (bmv; b1, b2, b3, and b4) contain a highly conserved 3' 200-nucleotide (nt) region encompassing the trna-like structure (tls) which is required for packaging in vitro (y. g. choi, t. w. dreher, and a. l. n. rao, proc. natl. acad. sci. usa 99:655-660, 2002). to validate these observations in vivo, we performed packaging assays using agrobacterium-mediated transient expression of rnas and coat protein (cp) (p. annamalai and a. l. n. rao, virology 33 ...200717005656
characterization of a novel 5' subgenomic rna3a derived from rna3 of brome mosaic bromovirus.the synthesis of 3' subgenomic rna4 (sgrna4) by initiation from an internal sg promoter in the rna3 segment was first described for brome mosaic bromovirus (bmv), a model tripartite positive-sense rna virus (w. a. miller, t. w. dreher, and t. c. hall, nature 313:68-70, 1985). in this work, we describe a novel 5' sgrna of bmv (sgrna3a) that we propose arises by premature internal termination and that encapsidates in bmv virions. cloning and sequencing revealed that, unlike any other bmv rna segme ...200617005659
catalytic core of alphavirus nonstructural protein nsp4 possesses terminal adenylyltransferase activity.the rna-dependent rna polymerase nsp4 is an integral part of the alphavirus replication complex. to define the role of nsp4 in viral rna replication and for a structure-function analysis, we expressed sindbis virus nsp4 in escherichia coli. the core catalytic domain of nsp4 (delta97nsp4, a deletion of the n-terminal 97 amino acids), which consists of the predicted polymerase domain containing the gdd amino acid motif required for viral rna synthesis, was stable against proteolytic degradation du ...200617005674
trans regulation of cap-independent translation by a viral subgenomic rna.many positive-strand rna viruses generate 3'-coterminal subgenomic mrnas to allow translation of 5'-distal open reading frames. it is unclear how viral genomic and subgenomic mrnas compete with each other for the cellular translation machinery. translation of the uncapped barley yellow dwarf virus genomic rna (grna) and subgenomic rna1 (sgrna1) is driven by the powerful cap-independent translation element (bte) in their 3' untranslated regions (utrs). the bte forms a kissing stem-loop interactio ...200617005682
rabies virus infection of primary neuronal cultures and adult mice: failure to demonstrate evidence of excitotoxicity.cultures derived from the cerebral cortices and hippocampi of 17-day-old mouse fetuses infected with the cvs strain of rabies virus showed loss of trypan blue exclusion, morphological apoptotic features, and activated caspase 3 expression, indicating apoptosis. the nmda (n-methyl-d-aspartate acid) antagonists ketamine (125 microm) and mk-801 (60 microm) were found to have no significant neuroprotective effect on cvs-infected neurons, while the caspase inhibitor ac-asp-glu-val aspartic acid aldeh ...200617005706
pkcdelta alternatively spliced isoforms modulate cellular apoptosis in retinoic acid-induced differentiation of human nt2 cells and mouse embryonic stem cells.nt2 cells are a human teratocarcinoma cell line that, upon treatment with retinoic acid (ra), begin differentiating into a neuronal phenotype. the transformation of undifferentiated nt2 cells into hnt neurons presents an opportunity to investigate the mechanisms involved in neurogenesis because a key component is cell apoptosis, which is essential for building neural networks. protein kinase cdelta (pkcdelta) plays an important role as a mediator of cellular apoptosis in response to various stim ...200617017122
indolopyridones inhibit human immunodeficiency virus reverse transcriptase with a novel mechanism of action.we have discovered a novel class of human immunodeficiency virus (hiv) reverse transcriptase (rt) inhibitors that block the polymerization reaction in a mode distinct from those of the nucleoside or nucleotide rt inhibitors (nrtis) and nonnucleoside rt inhibitors (nnrtis). for this class of indolopyridone compounds, steady-state kinetics revealed competitive inhibition with respect to the nucleotide substrate. despite substantial structural differences with classical chain terminators or natural ...200617020946
activity- and mtor-dependent suppression of kv1.1 channel mrna translation in dendrites.mammalian target of rapamycin (mtor) is implicated in synaptic plasticity and local translation in dendrites. we found that the mtor inhibitor, rapamycin, increased the kv1.1 voltage-gated potassium channel protein in hippocampal neurons and promoted kv1.1 surface expression on dendrites without altering its axonal expression. moreover, endogenous kv1.1 mrna was detected in dendrites. using kv1.1 fused to the photoconvertible fluorescence protein kaede as a reporter for local synthesis, we obser ...200617023663
manipulating kv4.2 identifies a specific component of hippocampal pyramidal neuron a-current that depends upon kv4.2 expression.the somatodendritic a-current, i(sa), in hippocampal ca1 pyramidal neurons regulates the processing of synaptic inputs and the amplitude of back propagating action potentials into the dendritic tree, as well as the action potential firing properties at the soma. in this study, we have used rna interference and over-expression to show that expression of the kv4.2 gene specifically regulates the i(sa) component of a-current in these neurons. in dissociated hippocampal pyramidal neuron cultures, or ...200617026528
mutagenesis of the la crosse virus glycoprotein supports a role for gc (1066-1087) as the fusion peptide.the la crosse virus (lacv) m segment encodes two glycoproteins (gn and gc), and plays a critical role in the neuropathogenesis of lacv infection as the primary determinant of neuroinvasion. a recent study from our group demonstrated that the region comprising the membrane proximal two-thirds of gc, amino acids 860-1442, is critical in mediating lacv fusion and entry. furthermore, computational analysis identified structural similarities between a portion of this region, amino acids 970-1350, and ...200717027056
identification of japanese encephalitis virus-inducible genes in mouse brain and characterization of garg39/ifit2 as a microtubule-associated protein.several mouse central nervous system genes have been identified that are differentially regulated during japanese encephalitis virus (jev) infection, including those which have not been reported to be induced by any other neurotropic virus. interestingly, approximately 80 % of jev-inducible genes identified in this study are also induced by sindbis virus, indicating activation of common host signalling pathways by these two viruses, despite their diverse life cycles. one of these, the glucocorti ...200617030862
next-generation optical technologies for illuminating genetically targeted brain circuits.emerging technologies from optics, genetics, and bioengineering are being combined for studies of intact neural circuits. the rapid progression of such interdisciplinary "optogenetic" approaches has expanded capabilities for optical imaging and genetic targeting of specific cell types. here we explore key recent advances that unite optical and genetic approaches, focusing on promising techniques that either allow novel studies of neural dynamics and behavior or provide fresh perspectives on clas ...017035522
antilipopolysaccharide factor interferes with white spot syndrome virus replication in vitro and in vivo in the crayfish pacifastacus leniusculus.in a study of genes expressed differentially in the freshwater crayfish pacifastacus leniusculus infected experimentally with the white spot syndrome virus (wssv), one protein, known as antilipopolysaccharide factor (alf), was chosen, among those whose transcript levels increased upon viral infection, for further studies. alf rna interference (rnai) experiments in whole animals and in cell cultures indicated that alf can protect against wssv infection, since knockdown of alf by rnai specifically ...200617041217
identification of linear heparin-binding peptides derived from human respiratory syncytial virus fusion glycoprotein that inhibit infectivity.it has been shown previously that the fusion glycoprotein of human respiratory syncytial virus (rsv-f) interacts with cellular heparan sulfate. synthetic overlapping peptides derived from the f-protein sequence of rsv subtype a (strain a2) were tested for their ability to bind heparin using heparin-agarose affinity chromatography (haac). this evaluation identified 15 peptides representing eight linear heparin-binding domains (hbds) located within f1 and f2 and spanning the protease cleavage acti ...200717050595
a chimeric alphavirus rna replicon gene-based vaccine for human parainfluenza virus type 3 induces protective immunity against intranasal virus challenge.parainfluenza virus type 3 (piv3) infections continue to be a significant health risk for infants, young children, and immunocompromised adults. we describe a gene-based vaccine strategy against piv3 using replication-defective alphavirus vectors. these rna replicon vectors, delivered as virus-like particles and expressing the piv3 hemagglutinin-neuraminidase glycoprotein, were shown to be highly immunogenic in mice and hamsters, inducing piv3-specific neutralizing antibody responses. importantl ...200717052811
functional role of aspartic proteinase cathepsin d in insect metamorphosis.metamorphosis is a complex, highly conserved and strictly regulated development process that involves the programmed cell death of obsolete larval organs. here we show a novel functional role for the aspartic proteinase cathepsin d during insect metamorphosis.200617062167
antibody responses against hiv in rhesus macaques following combinations of mucosal and systemic immunizations with chimeric alphavirus-based replicon particles.mucosal and systemic transmission of hiv is prevalent. therefore, mucosal followed by parenteral immunizations with chimeric vs. complete alphavirus-based replicon particles, encoding an hiv envelope glycoprotein, were tested. female rhesus macaques were immunized intranasally and then intramuscularly. following the immunizations, enhanced mucosal and systemic antibody responses were detected with the chimeric compared to the complete replicon particles. although similar proportions of the same ...200617067269
characterization of immune responses elicited in macaques immunized sequentially with chimeric vee/sin alphavirus replicon particles expressing sivgag and/or hivenv and with recombinant hivgp140env protein.in the present study, macaques were coimmunized with veerep/sinenv chimeric alphavirus replicon particles expressing sivp55gag and hivdeltav2gp140env or only with replicon particles expressing hivdeltav2gp140env. all animals were subsequently immunized with recombinant trimeric hivdeltav2gp140env protein. during alphavirus immunization, anti-sivgag and anti-hivenv-specific interferon (ifn)-gamma responses, as well as high titers of anti-hivenv binding (gp120 but not gp41 specific) and anti-hiv n ...200617067273
differential induction of type i interferon responses in myeloid dendritic cells by mosquito and mammalian-cell-derived alphaviruses.dendritic cells (dcs) are an important early target cell for many mosquito-borne viruses, and in many cases mosquito-cell-derived arboviruses more efficiently infect dcs than viruses derived from mammalian cells. however, whether mosquito-cell-derived viruses differ from mammalian-cell-derived viruses in their ability to induce antiviral responses in the infected dendritic cell has not been evaluated. in this report, alphaviruses, which are mosquito-borne viruses that cause diseases ranging from ...200717079324
arc/arg3.1 interacts with the endocytic machinery to regulate ampa receptor trafficking.arc/arg3.1 is an immediate-early gene whose mrna is rapidly transcribed and targeted to dendrites of neurons as they engage in information processing and storage. moreover, arc/arg3.1 is known to be required for durable forms of synaptic plasticity and learning. despite these intriguing links to plasticity, arc/arg3.1's molecular function remains enigmatic. here, we demonstrate that arc/arg3.1 protein interacts with dynamin and specific isoforms of endophilin to enhance receptor endocytosis. arc ...200617088211
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