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polysulfonates derived from metal thiolate complexes as inhibitors of hiv-1 and various other enveloped viruses in vitro.sodium 2-mercaptoethanesulfonate reacts with the metal ions pd(ii), pt(ii), ag(i), cd(ii) and zn(ii) to yield complexes containing multiple anionic sulfonate sites. on the basis of spectroscopic and other analytical data the complexes were assigned the tentative molecular formulas: pd6(sch2ch2so3na)12, ptn(sch2ch2so3na)2n+2, agn(sch2ch2so3na)n, na2zn4(sch2ch2so3na)10, and na2cd4(sch2ch2so3na)10. the complexes displayed a variety of differences in activity towards dna and rna viruses. the platinu ...200212448691
in vivo antitumor activity of sindbis viral vectors.sindbis virus, a blood-borne virus transmitted by mosquitoes, has been used as a vector to efficiently express exogenous genes in vitro and in vivo and to induce apoptosis. because sindbis virus infects mammalian cells by interacting with the high-affinity laminin receptors, which are expressed at higher levels in several human cancers than in normal cells, we determined whether a sindbis viral vector could be used to target cancers in vivo.200212464651
study of caspase inhibitors for limiting death in mammalian cell culture.apoptosis in mammalian cell culture is associated with decreased bioproduct yields and can be inhibited through altering the intracellular signaling pathways mediating programmed cell death. in this study, we evaluated the capacity to inhibit caspases to maintain high viable cell numbers in cho and 293 cultures. two genetic caspase inhibitors, xiap and crma, were examined along with a mutant of each, xiap-bir123nc, which contains three bir domains but lacks the ring finger, and crma-dqmd, which ...200312474256
transcription strategy in a closterovirus: a novel 5'-proximal controller element of citrus tristeza virus produces 5'- and 3'-terminal subgenomic rnas and differs from 3' open reading frame controller elements.citrus tristeza virus (ctv) produces more than thirty 3'- or 5'-terminal subgenomic rnas (sgrnas) that accumulate to various extents during replication in protoplasts and plants. among the most unusual species are two abundant populations of small 5'-terminal sgrnas of approximately 800 nucleotides (nt) termed low-molecular-weight tristeza (lmt1 and lmt2) rnas. remarkably, ctv replicons with all 10 3' genes deleted produce only the larger lmt1 rnas. these 5'-terminal positive-sense sgrnas do not ...200312477839
poliovirus-induced apoptosis is reduced in cells expressing a mutant cd155 selected during persistent poliovirus infection in neuroblastoma cells.poliovirus (pv) can establish persistent infections in human neuroblastoma imr-32 cells. we previously showed that during persistent infection, specific mutations were selected in the first extracellular domain of the pv receptor (cd155) of these cells (n. pavio, t. couderc, s. girard, j. y. sgro, b. blondel, and f. colbère-garapin, virology 274:331-342, 2000). these mutations included the ala 67 --> thr substitution, corresponding to a previously described allelic form of the pv receptor. the m ...200312477887
small interfering rna-mediated inhibition of hepatitis c virus replication in the human hepatoma cell line huh-7. 200312477890
enhanced immunogenicity to mycobacterium tuberculosis by vaccination with an alphavirus plasmid replicon expressing antigen 85a.the immunogenicity of a plasmid dna vaccine incorporating sindbis virus rna replicase functions (psincp) and expressing antigen 85a (ag85a) from mycobacterium tuberculosis was compared with a conventional plasmid dna vector encoding ag85a. psincp-85a was highly immunogenic in mice and gave enhanced long-term protection against m. tuberculosis compared with the conventional vector.200312496215
alphavirus-based dna vaccine breaks immunological tolerance by activating innate antiviral pathways.cancer vaccines targeting 'self' antigens that are expressed at consistently high levels by tumor cells are potentially useful in immunotherapy, but immunological tolerance may block their function. here, we describe a novel, naked dna vaccine encoding an alphavirus replicon (self-replicating mrna) and the self/tumor antigen tyrosinase-related protein-1. unlike conventional dna vaccines, this vaccine can break tolerance and provide immunity to melanoma. the vaccine mediates production of double- ...200312496961
antiviral effect and virus-host interactions in response to alpha interferon, gamma interferon, poly(i)-poly(c), tumor necrosis factor alpha, and ribavirin in hepatitis c virus subgenomic replicons.the recently developed hepatitis c virus (hcv) subgenomic replicon system was utilized to evaluate the efficacy of several known antiviral agents. cell lines that persistently maintained a genotype 1b replicon were selected. the replicon resident in each cell line had acquired adaptive mutations in the ns5a region that increased colony-forming efficiency, and some replicons had acquired ns3 mutations that alone did not enhance colony-forming efficiency but were synergistic with ns5a mutations. a ...200312502825
an attenuating mutation in nsp1 of the sindbis-group virus s.a.ar86 accelerates nonstructural protein processing and up-regulates viral 26s rna synthesis.the sindbis-group alphavirus s.a.ar86 encodes a threonine at nonstructural protein 1 (nsp1) 538 that is associated with neurovirulence in adult mice. mutation of the nsp1 538 thr to the consensus ile found in nonneurovirulent sindbis-group alphaviruses attenuates s.a.ar86 for adult mouse neurovirulence, while introduction of thr at position 538 in a nonneurovirulent sindbis virus background confers increased neurovirulence (m. t. heise et al., j. virol. 74:4207-4213, 2000). since changes in the ...200312502831
glycosaminoglycan binding properties of natural venezuelan equine encephalitis virus isolates.equine-virulent, epidemic/epizootic strains of venezuelan equine encephalitis (vee) virus (veev) arise via mutation of progenitor enzootic strains that replicate poorly in equines. sequencing studies have implicated positively charged amino acids on the surface of the e2 envelope glycoprotein in the acquisition of equine virulence and viremia potential, suggesting that changes in binding to cell surface glycosaminoglycans (gags) may mediate vee emergence. therefore, we evaluated the binding of n ...200312502837
hepatitis c virus f protein is a short-lived protein associated with the endoplasmic reticulum.hepatitis c virus (hcv) f protein is a newly discovered hcv gene product that is expressed by translational ribosomal frameshift. little is known about the biological properties of this protein. by performing pulse-chase labeling experiments, we demonstrate here that the f protein is a labile protein with a half-life of <10 min in huh7 hepatoma cells and in vitro. the half-life of the f protein could be substantially increased by proteasome inhibitors, suggesting that the rapid degradation of th ...200312502871
alphavirus cdna-based expression vectors: effects of rna transcription and nuclear export.the construction of layered dna-rna replicons has facilitated and expanded the use of alphavirus vectors to vaccine development, construction of packaging cell lines and long-term heterologous gene expression. in these vector systems, the alphavirus replicon is under the control of a strong rna polymerase ii promoter and replicon rna is transcribed from dna before transport to the cytoplasm. efficient rna amplification catalyzed by the viral replicase results in high levels of mrna and the recom ...200312514804
anti-sindbis activity of flavanones hesperetin and naringenin.the effect of hesperetin, naringenin and its glycoside form on the sindbis neurovirulent strain (nsv) replication in vitro was studied. all flavanones tested were not cytotoxic on baby hamster cells 21 clone 15 (bhk-21). antiviral effect was evaluated by a colorimetric assay using mtt (3-(4,5 dimethylthiazol-2-yl)-2,5-dipheyl-tetrazolium bromide) and by plaque reduction assay. hesperetin and naringenin had inhibitory activity on nsv infection. the 50% inhibitory doses (id(50%)) of both compounds ...200312520185
properly folded nonstructural polyprotein directs the semliki forest virus replication complex to the endosomal compartment.the late rna synthesis in alphavirus-infected cells, generating plus-strand rnas, takes place on cytoplasmic vacuoles (cpvs), which are modified endosomes and lysosomes. the cytosolic surface of cpvs consists of regular membrane invaginations or spherules, which are the sites of rna synthesis (p. kujala, a. ikäheimonen, n. ehsani, h. vihinen, p. auvinen, and l. kääriäinen j. virol. 75:3873-3884, 2001). to understand how cpvs arise, we have expressed the individual semliki forest virus (sfv) nons ...200312525603
alphavirus minus-strand synthesis and persistence in mouse embryo fibroblasts derived from mice lacking rnase l and protein kinase r.we report our studies to probe the possible role of the host response to double-stranded rna in cessation of alphavirus minus-strand synthesis. mouse embryo fibroblasts (mef) from mx1-deficient mice that also lack either the protein kinase r (pkr) or the latent rnase l or both pkr and rnase l were screened. in rnase l-deficient but not wild-type or pkr-deficient mef, there was continuous synthesis of minus-strand templates and the formation of new replication complexes producing viral plus stran ...200312525614
antibody-mediated targeting of an adenovirus vector modified to contain a synthetic immunoglobulin g-binding domain in the capsid.adenovirus vectors have been targeted to different cell types by genetic modification of the capsid or by using recombinant or chemically engineered adaptor molecules. however, both genetic capsid modifications and bridging adaptors have to be specifically tailored for each particular targeting situation. here, we present an efficient and versatile strategy allowing the direct use of monoclonal antibodies against cell surface antigens for targeting of adenovirus vectors. a synthetic 33-amino-aci ...200312525644
fine mapping of a cis-acting sequence element in yellow fever virus rna that is required for rna replication and cyclization.we present fine mapping of a cis-acting nucleotide sequence found in the 5' region of yellow fever virus genomic rna that is required for rna replication. there is evidence that this sequence interacts with a complementary sequence in the 3' region of the genome to cyclize the rna. replicons were constructed that had various deletions in the 5' region encoding the capsid protein and were tested for their ability to replicate. we found that a sequence of 18 nucleotides (residues 146 to 163 of the ...200312525663
unique inflammatory rna profiles of microglia in creutzfeldt-jakob disease.previous studies in creutzfeldt-jakob disease (cjd) have shown that myeloid cells in the periphery as well as derivative microglial cells in the brain are infectious. microglia can show an activated phenotype before prion protein (prp) pathology is detectable in brain, and isolated infectious microglia contain very little prp. to find whether a set of inflammatory genes are significantly induced or suppressed with infection, we analyzed rna from isolated microglia with relevant cdna arrays, and ...200312525699
entry of alphaviruses at the plasma membrane converts the viral surface proteins into an ion-permeable pore that can be detected by electrophysiological analyses of whole-cell membrane currents.alphaviruses are small enveloped viruses that have been used extensively as model enveloped viruses. during infection, virus particles are taken up into endosomes, where a low ph activates the viral fusion protein, e1. fusion of the viral and the endosomal membranes releases the viral core into the cytoplasm where cores are disassembled by interaction with 60s ribosomal subunits. recently, we have shown that in vitro this disassembly is strongly stimulated by low ph. we have proposed that after ...200312533714
long-term potentiation in the hippocampal ca1 area and dentate gyrus plays different roles in spatial learning.nmda receptor-dependent long-term potentiation (ltp) at hippocampal synapses has been considered a crucial component of the cellular basis for learning and memory. this form of ltp occurs in excitatory synapses in both the ca1 area and the dentate gyrus in the hippocampus. however, differential roles of ltp in these areas have not yet been identified. to address this issue, we enhanced the degree of ltp by expressing ca2+-permeable ampa receptors at either hippocampal ca1 or dentate gyrus synaps ...200312542671
modification of the 5' terminus of sindbis virus genomic rna allows nsp4 rna polymerases with nonaromatic amino acids at the n terminus to function in rna replication.we have previously shown that sindbis virus rna polymerase requires an n-terminal aromatic amino acid or histidine for wild-type or pseudo-wild-type function; mutant viruses with a nonaromatic amino acid at the n terminus of the polymerase, but which are otherwise wild type, are unable to produce progeny viruses and will not form a plaque at any temperature tested. we now show that such mutant polymerases can function to produce progeny virus sufficient to form plaques at both 30 and 40 degrees ...200312551967
the 64-kilodalton capsid protein homolog of beet yellows virus is required for assembly of virion tails.the filamentous virion of the closterovirus beet yellows virus (byv) consists of a long body formed by the major capsid protein (cp) and a short tail composed of the minor capsid protein (cpm) and the virus-encoded hsp70 homolog. by using nano-liquid chromatography-tandem mass spectrometry and biochemical analyses, we show here that the byv 64-kda protein (p64) is the fourth integral component of byv virions. the n-terminal domain of p64 is exposed at the virion surface and is accessible to anti ...012551975
kinetics of virus-specific cd8+ -t-cell expansion and trafficking following central nervous system infection.cd8+ t cells control acute infection of the central nervous system (cns) by neurotropic mouse hepatitis virus but do not suffice to achieve sterile immunity. to determine the lag between t-cell priming and optimal activity within the cns, the accumulation of virus-specific cd8+ t cells in the cns relative to that in peripheral lymphoid organs was assessed by using gamma interferon-specific elispot assays and class i tetramer staining. virus-specific cd8+ t cells were first detected in the cervic ...200312552021
individual expression of sindbis virus glycoproteins. e1 alone promotes cell fusion.the envelope of alphavirus particles contains two major glycoproteins, e1 and e2, that participate in virus entry and assembly of new virus particles. interactions between these glycoproteins determine their correct functioning. the expression of each glycoprotein in the absence of the other counterpart was achieved by means of electroporation of modified sindbis virus (sv) genomes. in addition, in trans coexpression of both glycoproteins was also tested in bhk cells. synthesis of the e1 glycopr ...200312573591
nucleocapsid-independent specific viral rna packaging via viral envelope protein and viral rna signal.for any of the enveloped rna viruses studied to date, recognition of a specific rna packaging signal by the virus's nucleocapsid (n) protein is the first step described in the process of viral rna packaging. in the murine coronavirus a selective interaction between the viral transmembrane envelope protein m and the viral ribonucleoprotein complex, composed of n protein and viral rna containing a short cis-acting rna element, the packaging signal, determines the selective rna packaging into virus ...012584316
the avian retrovirus avian sarcoma/leukosis virus subtype a reaches the lipid mixing stage of fusion at neutral ph.we previously showed that the envelope glycoprotein (enva) of avian sarcoma/leukosis virus subtype a (aslv-a) binds to liposomes at neutral ph following incubation with its receptor, tva, at >or=22 degrees c. we also provided evidence that aslv-c fuses with cells at neutral ph. these findings suggested that receptor binding at neutral ph and >or=22 degrees c is sufficient to activate env for fusion. a recent study suggested that two steps are necessary to activate avian retroviral envs: receptor ...200312584331
cellular proteins from human monocytes bind to dengue 4 virus minus-strand 3' untranslated region rna.the synthesis of plus and minus rna strands of several rna viruses requires as a first step the interaction of some viral regulatory sequences with cellular and viral proteins. the dengue 4 virus genome, a single-stranded, positive-polarity rna, is flanked by two untranslated regions (utr) located in the 5' and 3' ends. the 3'utr in the minus-strand rna [3'utr (-)] has been thought to function as a promoter for the synthesis of plus-strand rna. to study the initial interaction between this 3'utr ...200312584332
subcellular localization of herpes simplex virus type 1 ul51 protein and role of palmitoylation in golgi apparatus targeting.the herpes simplex virus type 1 (hsv-1) ul51 gene products are virion-associated phosphoproteins with apparent molecular masses of 27, 29, and 30 kda in hsv-1-infected cells. in this study, we have investigated the intracellular localization and distribution of ul51 protein both in infected cells and in transfected cells expressing only ul51. we found that this protein colocalized closely with golgi marker proteins such as the golgi-58k protein and gm130 in transfected cells expressing only ul51 ...200312584344
polystyrene derivatives substituted with arginine interact with babanki (togaviridae) and kedougou (flaviviridae) viruses.outbreaks of new or old diseases appear primarily in tropical zones such as africa, south and central america, or asia. among these diseases, those induced by arboviruses (the best known of which are being yellow fever, dengue, ebola, and sindbis) are under intensive observation by the world health organization. rapid isolation and identification of the viral species is the first step in the diagnosis, study, and control of epidemics. one major problem with the isolation of viruses is capturing ...200312601758
functional nmda receptor channels generated by nmdar2b gene transfer in rat cerebellar purkinje cells.the adult cerebellar purkinje cell is an exceptional neuron in the central nervous system in that it expresses high levels of nmdar1 (nr1) mrna without expressing any nmdar2 (nr2) mrnas. it has no functional nmda receptor (nmdar) channels, although it receives enormous numbers of excitatory inputs. despite the high level of nr1 mrna expression, the presence and localization of nr1 protein in mature purkinje cells are controversial. to examine the presence of nr1 protein and its ability to form f ...200312603279
induction of apoptosis by paramyxovirus simian virus 5 lacking a small hydrophobic gene.simian virus 5 (sv5) is a member of the paramyxovirus family, which includes emerging viruses such as hendra virus and nipah virus as well as many important human and animal pathogens that have been known for years. sv5 encodes eight known viral proteins, including a small hydrophobic integral membrane protein (sh) of 44 amino acids. sv5 without the sh gene (rsv5deltash) is viable, and growth of rsv5deltash in tissue culture cells and viral protein and mrna production in rsv5deltash-infected cel ...200312610112
interactions between the transmembrane segments of the alphavirus e1 and e2 proteins play a role in virus budding and fusion.the alphavirus envelope is built by heterodimers of the membrane proteins e1 and e2. the complex is formed as a p62e1 precursor in the endoplasmic reticulum. during transit to the plasma membrane (pm), it is cleaved into mature e1-e2 heterodimers, which are oligomerized into trimeric complexes, so-called spikes that bind both to each other and, at the pm, also to nucleocapsid (nc) structures under the membrane. these interactions drive the budding of new virus particles from the cell surface. th ...200312610119
the 5'-end sequence of the genome of aichi virus, a picornavirus, contains an element critical for viral rna encapsidation.picornavirus positive-strand rnas are selectively encapsidated despite the coexistence of viral negative-strand rnas and cellular rnas in infected cells. however, the precise mechanism of the rna encapsidation process in picornaviruses remains unclear. here we report the first identification of an rna element critical for encapsidation in picornaviruses. the 5' end of the genome of aichi virus, a member of the family picornaviridae, folds into three stem-loop structures (sl-a, sl-b, and sl-c, fr ...200312610129
alphavirus vectors as tools in cancer gene therapy.alphavirus vectors, particularly those based on the replicon of semliki forest virus, have shown great potential as gene delivery vehicles for various applications in cancer gene therapy. the rapid production of high-titer recombinant sfv particles, which show impressive transduction rates in various mammalian cell lines, primary cultures and in vivo, results in high levels of transgene expression. additionally, sfv vectors induce apoptosis in transduced host cells, which can further increase th ...200212614181
experience strengthening transmission by driving ampa receptors into synapses.the mechanisms underlying experience-dependent plasticity in the brain may depend on the ampa subclass of glutamate receptors (ampa-rs). we examined the trafficking of ampa-rs into synapses in the developing rat barrel cortex. in vivo gene delivery was combined with in vitro recordings to show that experience drives recombinant glur1, an ampa-r subunit, into synapses formed between layer 4 and layer 2/3 neurons. moreover, expression of the glur1 cytoplasmic tail, a construct that inhibits synapt ...200312624270
facilitation of dendritic mrna transport by cpeb.in neurons, the proteins derived from mrnas localized in dendrites have been implicated in synaptic plasticity. the cytoplasmic polyadenylation element (cpe), a cis element in the 3'-utrs of specific dendritic mrnas, promotes cytoplasmic polyadenylation-induced translation in response to synaptic stimulation. here, we demonstrate that the cpe and its binding protein cpeb facilitate mrna transport to dendrites. in rat hippocampal neurons infected with recombinant viruses, the cpe is sufficient to ...200312629046
american genotype structures decrease dengue virus output from human monocytes and dendritic cells.the dengue virus type 2 structures probably involved in human virulence were previously defined by sequencing the complete genome of both american and southeast (se) asian genotype templates in patient serum (k. c. leitmeyer et al., j. virol. 73:4738-4747, 1999). we have now evaluated the effects of introducing a mutation in the envelope glycoprotein (e) gene and/or replacement of 5'- and 3'-nontranslated regions on dengue virus replication in human primary cell cultures. a series of chimeric in ...200312634353
hepatitis c virus glycoproteins interact with dc-sign and dc-signr.dc-sign and dc-signr are two closely related membrane-associated c-type lectins that bind human immunodeficiency virus (hiv) envelope glycoprotein with high affinity. binding of hiv to cells expressing dc-sign or dc-signr can enhance the efficiency of infection of cells coexpressing the specific hiv receptors. dc-sign is expressed on some dendritic cells, while dc-signr is localized to certain endothelial cell populations, including hepatic sinusoidal endothelial cells. we found that soluble ver ...200312634366
the abundant nuclear enzyme parp participates in the life cycle of simian virus 40 and is stimulated by minor capsid protein vp3.the abundant nuclear enzyme poly(adp-ribose) polymerase (parp) functions in dna damage surveillance and repair and at the decision between apoptosis and necrosis. here we show that parp binds to simian virus 40 (sv40) capsid proteins vp1 and vp3. furthermore, its enzymatic activity is stimulated by vp3 but not by vp1. experiments with purified mutant proteins demonstrated that the parp binding domain in vp3 is localized to the 35 carboxy-terminal amino acids, while a larger peptide of 49 amino a ...200312634384
engineering the transmissible gastroenteritis virus genome as an expression vector inducing lactogenic immunity.the genome of the coronavirus transmissible gastroenteritis virus (tgev) has been engineered as an expression vector with an infectious cdna. the vector led to the efficient (>40 micro g/10(6) cells) and stable (>20 passages) expression of a heterologous gene (green fluorescent protein [gfp]), driven by the transcription-regulating sequences (trs) of open reading frame (orf) 3a inserted in the site previously occupied by the nonessential orfs 3a and 3b. expression levels driven by this trs were ...200312634392
diverse dengue type 2 virus populations contain recombinant and both parental viruses in a single mosquito host.envelope (e) protein genes sampled from populations of dengue 2 (den-2) virus in individual aedes aegypti mosquitoes and in serum from dengue patients were copied to cdna, cloned, and sequenced. the nucleotide sequences of the e genes in more than 70% of the clones differed from the consensus sequence for the corresponding virus population at up to 11 sites, and 24 of the 94 clones contained at least one stop codon. virus populations recovered up to 2 years apart yielded clones with similar poly ...200312634407
development of an orally infectious sindbis virus transducing system that efficiently disseminates and expresses green fluorescent protein in aedes aegypti.we have constructed an orally infectious sindbis virus, me2/5'2j/gfp, that expresses green fluorescent protein (gfp) in the midgut of aedes aegypti and in other tissues as the virus disseminates. this virus has two unique features that are improvements over the sin-based expression systems currently used in mosquitoes. first, a subgenomic rna promoter and gfp coding sequence is located 5'- to the second subgenomic promoter and structural genes of the virus. second, the e2 glycoprotein gene of te ...200312653932
foamy virus envelope glycoprotein-mediated entry involves a ph-dependent fusion process.in general, enveloped viruses use two different entry strategies and are classified accordingly into ph-dependent and ph-independent viruses. different members of the retrovirus family use one or the other strategy. little is known about the uptake of foamy viruses (fv), a special group of retroviruses, into the target cells. in this study, we examined the ph dependence of fv entry by analyzing fv envelope glycoprotein (env)-mediated infection of target cells with murine leukemia virus or fv vec ...200312663779
kinetics of cd4+ and cd8+ memory t-cell responses during hepatitis c virus rechallenge of previously recovered chimpanzees.the immunological correlates of hepatitis c virus (hcv)-specific immunity are not well understood. antibodies to hcv structural proteins do not appear to play a key role in clearance of the virus and do not persist after recovery. here, we studied the kinetics of the cellular immune responses of three hcv-recovered chimpanzees during rechallenge with increasing doses of homologous hcv. although hcv envelope antibodies remained undetectable throughout the rechallenge, all animals mounted rapid hc ...200312663785
complexes of poliovirus serotypes with their common cellular receptor, cd155.structures of all three poliovirus (pv) serotypes (pv1, pv2, and pv3) complexed with their cellular receptor, pv receptor (pvr or cd155), were determined by cryoelectron microscopy. both glycosylated and fully deglycosylated cd155 exhibited similar binding sites and orientations in the viral canyon for all three pv serotypes, showing that all three serotypes use a common mechanism for cell entry. difference maps between the glycosylated and deglycosylated cd155 complexes determined the sites of ...200312663789
morphological variants of sindbis virus produced by a mutation in the capsid protein.sindbis virus is a complex aggregate of rna, protein and lipid. the virus is organized as two nested t = 4 icosahedral protein shells between which is sandwiched a lipid bilayer. the virus rna resides within the inner protein shell. the inner protein shell is attached to the outer protein shell through contacts to proteins in the outer shell, which penetrate the lipid bilayer. the data presented in the following manuscript show that mutations in the capsid protein can result in the assembly of t ...200312667814
bak alters neuronal excitability and can switch from anti- to pro-death function during postnatal development.bak is a pro-apoptotic bcl-2 family protein that localizes to mitochondria. here we evaluate the function of bak in several mouse models of neuronal injury including neuronotropic sindbis virus infection, parkinson's disease, ischemia/stroke, and seizure. bak promotes or inhibits neuronal death depending on the specific death stimulus, neuron subtype, and stage of postnatal development. bak protects neurons from excitotoxicity and virus infection in the hippocampus. as mice mature, bak is conver ...200312689595
attenuated salmonella enterica serovar typhi and shigella flexneri 2a strains mucosally deliver dna vaccines encoding measles virus hemagglutinin, inducing specific immune responses and protection in cotton rats.measles remains a leading cause of child mortality in developing countries. residual maternal measles antibodies and immunologic immaturity dampen immunogenicity of the current vaccine in young infants. because cotton rat respiratory tract is susceptible to measles virus (mv) replication after intranasal (i.n.) challenge, this model can be used to assess the efficacy of mv vaccines. pursuing a new measles vaccine strategy that might be effective in young infants, we used attenuated salmonella en ...200312692223
luciferase imaging of a neurotropic viral infection in intact animals.the identification of viral determinants of virulence and host determinants of susceptibility to virus-induced disease is essential for understanding the pathogenesis of infection. obtaining this information requires infecting large numbers of animals to assay amounts of virus in a variety of organs and to observe the onset and progression of disease. as an alternative approach, we have used a murine model of viral encephalitis and an in vivo imaging system that can detect light generated by luc ...200312692235
human rhinovirus type 2 is internalized by clathrin-mediated endocytosis.using several approaches, we investigated the importance of clathrin-mediated endocytosis in the uptake of human rhinovirus serotype 2 (hrv2). by means of confocal immunofluorescence microscopy, we show that k(+) depletion strongly reduces hrv2 internalization. viral uptake was also substantially reduced by extraction of cholesterol from the plasma membrane with methyl-beta-cyclodextrin, which can inhibit clathrin-mediated endocytosis. in accordance with these data, overexpression of dynamin k44 ...200312692238
immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid r+win55,212.theiler murine encephalomyelitis virus-induced demyelinating disease (tmev-idd) is a mouse model of chronic-progressive multiple sclerosis (ms) characterized by th1-mediated cns demyelination and spastic hindlimb paralysis. existing ms therapies reduce relapse rates in 30% of relapsing-remitting ms patients, but are ineffective in chronic-progressive disease, and their effects on disability progression are unclear. experimental studies demonstrate cannabinoids are useful for symptomatic treatmen ...200312697742
modified apoptotic molecule (bid) reduces hepatitis c virus infection in mice with chimeric human livers.hepatitis c virus (hcv) encodes a polyprotein consisting of core, envelope (e1, e2, p7), and nonstructural polypeptides (ns2, ns3, ns4a, ns4b, ns5a, ns5b). the serine protease (ns3/ns4a), helicase (ns3), and polymerase (ns5b) constitute valid targets for antiviral therapy. we engineered bh3 interacting domain death agonist (bid), an apoptosis-inducing molecule, to contain a specific cleavage site recognized by the ns3/ns4a protease. cleavage of the bid precursor molecule by the viral protease ac ...200312704395
genetic screen for monitoring hepatitis c virus ns3 serine protease activity.we have developed a genetic system to monitor the activity of the hepatitis c virus (hcv) ns3 serine protease. this genetic system is based on the bacteriophage lambda regulatory circuit where the viral repressor ci is specifically cleaved to initiate the switch from lysogeny to lytic infection. an hcv protease-specific target, ns5a-5b, was inserted into the lambda phage ci repressor. the target specificity of the hcv ns5a-5b repressor was evaluated by coexpression of this repressor with a beta- ...200312709356
the prevalence of antibodies against sindbis-related (pogosta) virus in different parts of finland.to study the occurrence of sindbis-related (pogosta) disease in finland by serological means.200312709538
effects of collagen matrix on sindbis virus infection of bhk cells.the effects of extracellular matrix (ecm) components on the outcomes of alphavirus interaction with cells are not known. studies that address such interactions have to address several methodological difficulties, including: the survival of the cells within the matrix; the passage of the virus through the matrix to infect embedded cells; and the dissociation of cells and matrix into single-cell suspension, before and after virus infection, for quantitative analysis. herein, these issues were addr ...200312711058
sindbis virus vectors designed to express a foreign protein as a cleavable component of the viral structural polyprotein.alphavirus-based expression vectors commonly use a duplicated 26s promoter to drive expression of a foreign gene. here we describe an expression strategy in which the foreign sequences are linked to the gene encoding the 2a protease of foot-and-mouth disease virus and then inserted in frame between the capsid and e3 genes of sindbis virus. during replication, the 2a fusion protein is synthesized as a component of the viral structural polyprotein that is then released by intramolecular cleavages ...200312719552
effect of p38 mitogen-activated protein kinase on the replication of encephalomyocarditis virus.cellular phosphorylation events during viral infection are necessary for effective viral replication. encephalomyocarditis (emc) virus has been used for studies on the molecular mechanisms of viral replication, but little is known about the cellular signaling pathways involved. this investigation was initiated to determine whether mitogen-activated protein kinases (mapks), which are central components of signal transduction pathways in the regulation of cell proliferation, play a role in the rep ...200312719557
vesicular stomatitis viruses with rearranged genomes have altered invasiveness and neuropathogenesis in mice.transcription of vesicular stomatitis virus is controlled by the position of a gene relative to the single 3' genomic promoter: promoter-proximal genes are transcribed at higher levels than those in more 5' distal positions. in previous work, we generated viruses having rearranged gene orders. these viruses had the promoter-proximal gene that encodes the nucleocapsid protein, n, moved to the second or fourth position in the genome in combination with the glycoprotein gene, g, moved from its usua ...200312719567
human immunodeficiency virus type 1 envelope-mediated neuropathogenesis: targeted gene delivery by a sindbis virus expression vector.sindbis virus (sin) expression vectors offer the opportunity for studying neuropathogenesis because of their distinct neural cell tropism. here, we demonstrate that a recombinant sin vector expressing egfp (sinrep5-egfp) infected multiple cell types including neural cells from several species relevant to lentivirus pathogenesis with high levels of transgene expression. infection of human neurons by a recombinant sin (sinrep5-jrfl) expressing the full-length envelope from a neurovirulent human im ...200312726727
activation of fusion by the ser virus f protein: a low-ph-dependent paramyxovirus entry process.ser virus, a paramyxovirus closely related to simian virus 5, induces no syncytium formation. the ser virus f protein has a long cytoplasmic tail (ct), and truncation or mutations of the ct result in enhanced syncytium formation (s. seth, a. vincent, and r. w. compans, j. virol. 77:167-178, 2003; s. tong, m. li, a. vincent, r. w. compans, e. fritsch, r. beier, c. klenk, m. ohuchi, and h.-d. klenk, virology 301:322-333, 2002). we hypothesized that the presence of the long ct serves to stabilize t ...200312743308
prevalence of sindbis-related (pogosta) virus infections in patients with arthritis.to determine the role of pogosta virus as a triggering infection in non-specific arthritis.200312747277
[complete nucleotide sequence of the nonstructural gene of alphavirus yn87448 strain isolated in china and its relationship to other sindbis viruses].to determine the complete nucleotide sequence of the nonstructural gene of yn87448 virus stain which was firstly isolated from a female patient with fever in yunnan province in 1986, and identified as a member of alphavirus by the serological method.199912759966
hepatitis c virus glycoproteins mediate ph-dependent cell entry of pseudotyped retroviral particles.hiv pseudotypes bearing native hepatitis c virus (hcv) glycoproteins (strain h and con1) are infectious for the human hepatoma cell lines huh-7 and plc/pr5. infectivity depends on coexpression of both e1 and e2 glycoproteins, is ph-dependent, and can be neutralized by mabs mapping to amino acids 412-447 within e2. cell-surface expression of one or all of the candidate receptor molecules (cd81, low-density lipoprotein receptor, scavenger receptor class b type 1, and dendritic cell-specific interc ...200312761383
flavivirus capsid is a dimeric alpha-helical protein.the capsid proteins of two flaviviruses, yellow fever virus and dengue virus, were expressed in escherichia coli and purified to near homogeneity suitable for biochemical characterization and structure determination by nuclear magnetic resonance. the oligomeric properties of the capsid protein in solution were investigated. in the absence of nucleic acid, both proteins were predominantly dimeric in solution. further analysis of both proteins with far-uv circular dichroism spectroscopy indicated ...200312768036
structures of immature flavivirus particles.structures of prm-containing dengue and yellow fever virus particles were determined to 16 and 25 a resolution, respectively, by cryoelectron microscopy and image reconstruction techniques. the closely similar structures show 60 icosahedrally organized trimeric spikes on the particle surface. each spike consists of three prm:e heterodimers, where e is an envelope glycoprotein and prm is the precursor to the membrane protein m. the pre-peptide components of the prm proteins in each spike cover th ...200312773377
transduction of dominant negative atf-1 suppresses the px gene expression in joint fibroblastic cells derived from htlv-i transgenic rats.tax (p40tax) encoded by the env-px gene of human t-cell leukemia virus type i (htlv-i) interacts with cyclic adenosine-3',5'-monophosphate response element binding protein/activation transcription factor 1 (creb/atf-1) transcription factors of host cells and activates the viral long terminal repeat (ltr) promoter. this molecular interaction induces augmentation of viral gene expression and may result in development of htlv-i-associated diseases, including adult t-cell leukemia, htlv-i associated ...200312782019
assessing the feasibility of using neural precursor cells and peripheral blood mononuclear cells for detection of bioactive sindbis virus.viruses form a significant class of bio-threat agents. currently, the only method to determine the bioactivity of viruses in vitro is to measure viral and cellular responses after co-incubation of cells with virus. our goal is to find biomarkers for classification of agents, establishment of bioactivity, and/or prediction of disease outcomes. to begin development of a cell-based biosensor for detection of bioactive sindbis virus (sv), our model analyte, we surveyed the outcomes of sv interaction ...200312782470
developing baculovirus-insect cell expression systems for humanized recombinant glycoprotein production.the baculovirus-insect cell expression system is widely used to produce recombinant glycoproteins for many different biomedical applications. however, due to the fundamental nature of insect glycoprotein processing pathways, this system is typically unable to produce recombinant mammalian glycoproteins with authentic oligosaccharide side chains. this minireview summarizes our current understanding of insect protein glycosylation pathways and our recent efforts to address this problem. these effo ...012788624
virus entry, assembly, budding, and membrane rafts.as intracellular parasites, viruses rely heavily on the use of numerous cellular machineries for completion of their replication cycle. the recent discovery of the heterogeneous distribution of the various lipids within cell membranes has led to the proposal that sphingolipids and cholesterol tend to segregate in microdomains called membrane rafts. the involvement of membrane rafts in biosynthetic traffic, signal transduction, and endocytosis has suggested that viruses may also take advantage of ...012794191
nucleic acid-based immune system: the antiviral potential of mammalian rna silencing. 012805414
murine cytomegalovirus abortively infects human dendritic cells, leading to expression and presentation of virally vectored genes.dendritic cells (dc) are potent antigen-presenting cells that play a crucial role in antigen-specific immune responses. thus, the targeting of exogenous antigens to dc has become a popular approach for cancer immunotherapy and vaccine development. in this report, we studied the interplay between murine cytomegalovirus (mcmv) and human monocyte-derived dc. the results showed that an enhanced green fluorescent protein (egfp)-encoding, replication-competent mcmv vector underwent abortive infection ...200312805417
common host genes are activated in mouse brain by japanese encephalitis and rabies viruses.this study identified nine genes whose expression is upregulated in the central nervous system (cns) of mice during japanese encephalitis virus (jev) infection. these include: cathepsin s, oligoadenylate synthetase (oas), garg49/irg2, lymphocyte antigen-6a (ly-6a), macrophage activation gene-2 (mpa2), early growth response gene1 (egr1), pyrimidine 5'-nucleotidase (p5n), apolipoprotein d (apod) and stat1. activation of all nine genes during jev infection was confirmed by northern blot analysis. j ...200312810866
disc1 (disrupted-in-schizophrenia 1) is a centrosome-associated protein that interacts with map1a, mipt3, atf4/5 and nudel: regulation and loss of interaction with mutation.disrupted-in-schizophrenia 1 (disc1) is a novel gene associated with schizophrenia by multiple genetic studies. in order to determine how mutations in disc1 might cause susceptibility to schizophrenia, we undertook a comprehensive study of the cellular biology of disc1 in its full-length and disease-associated mutant forms. disc1 interacts by yeast two-hybrid, mammalian two-hybrid, and co-immunoprecipitation assays with multiple proteins of the centrosome and cytoskeletal system, including mipt3 ...200312812986
use of a sindbis virus dna-based expression vector for induction of protective immunity against pseudorabies virus in pigs.injection of plasmid dna encoding pseudorabies virus (prv) glycoproteins into pig muscle has been shown to result in protective immunity against lethal infection. nevertheless, such dna vaccines are still less efficient than some attenuated or killed live vaccines. one way to increase dna vaccine efficacy is to improve the vectorisation system at the molecular level, thereby enhancing the rate of in vivo-produced immunogen protein and consequently specific acquired immunity. the present study co ...200312814698
possible involvement of rap1 and ras in glutamatergic synaptic transmission.rap1a, first identified as a suppressor of transformed phenotype induced by an activated ras oncogene, is abundantly expressed in the brain. its neurophysiological function, however, is poorly understood. when an activated rap1a mutant (rap1-12v) or a dominant negative h-ras mutant (ras-17n) was expressed in ca1 neurons in cultured hippocampal slices using the sindbis virus-mediated gene transfer technique, nmda receptor current in response to schaffer collateral stimulation was suppressed. expr ...200312824760
nonstructural protein precursor ns4a/b from hepatitis c virus alters function and ultrastructure of host secretory apparatus.the nonstructural proteins of hepatitis c virus (hcv) have been shown previously to localize to the endoplasmic reticulum (er) when expressed singly or in the context of other hcv proteins. to determine whether the expression of hcv nonstructural proteins alters er function, we tested the effect of expression of ns2/3/4a, ns4a, ns4b, ns4a/b, ns4b/5a, ns5a, and ns5b from genotype 1b hcv on anterograde traffic from the er to the golgi apparatus. only the nominal precursor protein ns4a/b affected t ...200312829824
fitness of a turnip crinkle virus satellite rna correlates with a sequence-nonspecific hairpin and flanking sequences that enhance replication and repress the accumulation of virions.satc, a satellite rna associated with turnip crinkle virus (tcv), enhances the ability of the virus to colonize plants by interfering with stable virion accumulation (f. zhang and a. e. simon, unpublished data). previous results suggested that the motif1-hairpin (m1h), a replication enhancer on minus strands, forms a plus-strand hairpin flanked by ca-rich sequence that may be involved in enhancing systemic infection (g. zhang and a. e. simon, j. mol. biol. 326:35-48, 2003). in this study, sequen ...200312829828
extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted sindbis virus.viral infections of the central nervous system and immune responses to these infections cause a variety of neurological diseases. infection of weanling mice with sindbis virus causes acute nonfatal encephalomyelitis followed by clearance of infectious virus, but persistence of viral rna. infection with a neuroadapted strain of sindbis virus (nsv) causes fatal encephalomyelitis, but passive transfer of immune serum after infection protects from fatal disease and infectious virus is cleared. to de ...200312832200
human embryonic germ cell derivatives facilitate motor recovery of rats with diffuse motor neuron injury.we have investigated the potential of human pluripotent cells to restore function in rats paralyzed with a virus-induced motor neuronopathy. cells derived from embryonic germ cells, termed embryoid body-derived (ebd) cells, introduced into the csf were distributed extensively over the rostrocaudal length of the spinal cord and migrated into the spinal cord parenchyma in paralyzed, but not uninjured, animals. some of the transplanted human cells expressed the neuroglial progenitor marker nestin, ...200312832537
dna vaccines and apoptosis: to kill or not to kill? 012840054
a modified sindbis vector for prolonged gene expression in neurons.sindbis viruses have been widely used in neurobiology to express a variety of genes in cultured neurons, in cultured slices, and in vivo. they provide fast onset and high levels of expression of foreign genes, but the expression is limited to a short time window due to a shut-off of host protein synthesis. we have used a mutation in an essential gene (nsp2) of the life cycle of sindbis, which allows the functional analysis of changes in protein expression for >/=6 days after infection. this sind ...200312853440
p250gap, a novel brain-enriched gtpase-activating protein for rho family gtpases, is involved in the n-methyl-d-aspartate receptor signaling.n-methyl-d-aspartate (nmda) receptors regulate structural plasticity by modulating actin organization within dendritic spines. herein, we report identification and characterization of p250gap, a novel gtpase-activating protein for rho family proteins that interacts with the glurepsilon2 (nr2b) subunit of nmda receptors in vivo. the p250gap mrna was enriched in brain, with high expression in cortex, corpus striatum, hippocampus, and thalamus. within neurons, p250gap was highly concentrated in the ...200312857875
a heterologous coiled coil can substitute for helix i of the sindbis virus capsid protein.alphavirus core assembly proceeds along an assembly pathway involving a dimeric assembly intermediate. several regions of the alphavirus capsid protein have been implicated in promoting and stabilizing this dimerization, including a putative heptad repeat sequence named helix i. this sequence, which spans residues 38 to 55 of the sindbis virus capsid protein, was implicated in stabilizing dimeric contacts initiated through the c-terminal two-thirds of the capsid protein and nucleic acid. the stu ...200312857904
complete genomic sequence of the australian south-west genotype of sindbis virus: comparisons with other sindbis strains and identification of a unique deletion in the 3'-untranslated region.our previous studies have shown that two distinct genotypes of sindbis (sin) virus occur in australia. one of these, the oriental/australian type, circulates throughout most of the australian continent, whereas the recently identified south-west (sw) genetic type appears to be restricted to a distinct geographic region located in the temperate south-west of australia. we have now determined the complete nucleotide and translated amino acid sequences of a sw isolate of sin virus (sw6562) and perf ...200312876458
adaptation of puumala hantavirus to cell culture is associated with point mutations in the coding region of the l segment and in the noncoding regions of the s segment.we previously developed a model for studies on hantavirus host adaptation and initiated genetic analysis of puumala virus variants passaged in colonized bank voles and in cultured vero e6 cells. with the data presented in this paper, the sequence comparison of the wild-type and vero e6-adapted variants of puumala virus, strain kazan, has been completed. the only amino acid substitution that distinguished the two virus variants was found in the l protein, ser versus phe at position 2053. another ...200312885898
deletions in the putative cell receptor-binding domain of sindbis virus strain mre16 e2 glycoprotein reduce midgut infectivity in aedes aegypti.the sindbis virus (alphavirus; togaviridae) strain mre16 efficiently infects aedes aegypti mosquitoes that ingest a blood meal containing 8 to 9 log(10) pfu of virus/ml. however, a small-plaque variant of this virus, mre16sp, poorly infects mosquitoes after oral infection with an equivalent titer. to determine the genetic differences between mre16 and mre16sp viruses, we have sequenced the mre16sp structural genes and found a 90-nucleotide deletion in the e2 glycoprotein that spans the 3' end of ...200312885905
reovirus-induced alteration in expression of apoptosis and dna repair genes with potential roles in viral pathogenesis.reoviruses are a leading model for understanding cellular mechanisms of virus-induced apoptosis. reoviruses induce apoptosis in multiple cell lines in vitro, and apoptosis plays a key role in virus-induced tissue injury of the heart and brain in vivo. the activation of transcription factors nf-kappab and c-jun are key events in reovirus-induced apoptosis, indicating that new gene expression is critical to this process. we used high-density oligonucleotide microarrays to analyze cellular transcri ...200312885910
real-time imaging of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (ampa receptor) movements in neurons.the mechanisms that regulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (ampar) synthesis, transport, targeting and surface expression are of fundamental importance for fast excitatory neurotransmission and synaptic plasticity in the mammalian central nervous system. it has become apparent that these control processes involve complex sets of protein-protein interactions and many of the proteins responsible have been identified. we have been working to visualize ampar movem ...012887326
characterization of the intracellular transport of glur1 and glur2 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunits in hippocampal neurons.little is known about the dynamics of the dendritic transport of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (ampars) to synapses. here, using virally expressed green fluorescent protein (gfp)-glur1 and gfp-glur2 and confocal photobleach techniques we show near real-time movement of these subunits in living cultured hippocampal neurons. gfp-glur1 fluorescence was widely distributed throughout the extranuclear compartment with no evidence for discrete intracellular stores. ...200312909632
recombinant sindbis/venezuelan equine encephalitis virus is highly attenuated and immunogenic.venezuelan equine encephalitis virus (veev) is an important, naturally emerging zoonotic virus. veev was a significant human and equine pathogen for much of the past century, and recent outbreaks in venezuela and colombia (1995), with about 100,000 human cases, indicate that this virus still poses a serious public health threat. the live attenuated tc-83 vaccine strain of veev was developed in the 1960s using a traditional approach of serial passaging in tissue culture of the virulent trinidad d ...200312915543
complementation of a deletion in the rubella virus p150 nonstructural protein by the viral capsid protein.rubella virus (rub) replicons with an in-frame deletion of 507 nucleotides between two noti sites in the p150 nonstructural protein (deltanoti) do not replicate (as detected by expression of a reporter gene encoded by the replicon) but can be amplified by wild-type helper virus (tzeng et al., virology 289:63-73, 2001). surprisingly, virus with deltanoti was viable, and it was hypothesized that this was due to complementation of the noti deletion by one of the virion structural protein genes. int ...200312915564
low ph, caprylate incubation as a second viral inactivation step in the manufacture of albumin. parametric and validation studies.caprylate has long been used as a stabiliser for albumin solutions, as well as a precipitation agent for immunoglobulins, ceruloplasmin and more recently in removing contaminants during albumin purification. its virucidal properties have been explored and it has been proposed that the non-ionised form of the caprylate acid disrupts the integrity of the lipid bilayer and membrane associated proteins of enveloped viruses. the studies reported here further explore the use of this fatty acid to inac ...200312935811
antiviral effects of geranylgeranylacetone: enhancement of mxa expression and phosphorylation of pkr during influenza virus infection.a cyclic polyisoprenoid compound, geranylgeranylacetone (gga), has been used as antiulcer drug. gga is also a potent inducer of heat shock proteins (hsps). hsps are considered to induce an antiviral effect; however, the detailed mechanism is unknown. to determine whether gga might show antiviral activity and what the mechanism is, the effect of gga against influenza virus (strain pr8) infection in vivo and in vitro was investigated. the results demonstrated that gga treatment strongly suppressed ...200312936994
packaging of brome mosaic virus rna3 is mediated through a bipartite signal.the three genomic and a single subgenomic rna of brome mosaic virus (bmv), an rna virus infecting plants, are packaged by a single-coat protein (cp) into three morphologically indistinguishable icosahedral virions with t = 3 quasi-symmetry. genomic rnas 1 and 2 are packaged individually into separate particles whereas genomic rna3 and subgenomic rna4 (coat protein mrna) are copackaged into a single particle. we report here that packaging of dicistronic rna3 requires a bipartite signal. a highly ...200312941883
cis-acting elements required for efficient packaging of brome mosaic virus rna3 in barley protoplasts.brome mosaic virus (bmv) is a positive-sense rna plant virus, the tripartite genomic rnas of which are separately packaged into virions. rna3 is copackaged with subgenomic rna4. in barley protoplasts coinoculated with rna1 and rna2, an rna3 mutant with a 69-nucleotide (nt) deletion in the 3'-proximal region of the 3a open reading frame (orf) was very poorly packaged compared with other rna3 mutants and wild-type rna3, despite their comparable accumulation in the absence of coat protein. computer ...200312941908
t cells cause acute immunopathology and are required for long-term survival in mouse adenovirus type 1-induced encephalomyelitis.infection of adult c57bl/6 (b6) mice with mouse adenovirus type 1 (mav-1) results in dose-dependent encephalomyelitis. utilizing immunodeficient mice, we analyzed the roles of t cells, t-cell subsets, and t-cell-related functions in mav-1-induced encephalomyelitis. t cells, major histocompatibility complex (mhc) class i, and perforin contributed to acute disease signs at 8 days postinfection (p.i.). acute mav-1-induced encephalomyelitis was absent in mice lacking t cells and in mice lacking perf ...200312941916
synthesis, antiviral and cytotoxic activity of 6-bromo-2,3-disubstituted-4(3h)-quinazolinones.in the present study, a series of 6-bromo-2,3-disubstitued-4(3h)-quinazolinones was synthesized by condensation of 6-bromo-2-substituted-benzoxazin-4-one with trimethoprim, pyrimethamine and lamotrigine. the chemical structures of the synthesized compounds were confirmed by means of ir, (1)h-nmr and mass spectral and elemental analysis. the antiviral activity and cytotoxicity of the compounds were tested in e(6)sm (herpes simplex-1 kos, herpes simplex-1 tk-kos acv, herpes simplex-2 g, vaccinia v ...200312951471
an alphavirus replicon particle chimera derived from venezuelan equine encephalitis and sindbis viruses is a potent gene-based vaccine delivery vector.alphavirus replicon particle-based vaccine vectors derived from sindbis virus (sin), semliki forest virus, and venezuelan equine encephalitis virus (vee) have been shown to induce robust antigen-specific cellular, humoral, and mucosal immune responses in many animal models of infectious disease and cancer. however, since little is known about the relative potencies among these different vectors, we compared the immunogenicity of replicon particle vectors derived from two very different parental ...200312970424
glycoprotein of nonpathogenic rabies viruses is a key determinant of human cell apoptosis.we showed that, unlike pathogenic rabies virus (rv) strain cvs, attenuated rv strain era triggers the caspase-dependent apoptosis of human cells. furthermore, we observed that the induction of apoptosis is correlated with a particular virus antigen distribution: the overexpression of the viral g protein on the cell surface, with continuous localization on the cytoplasmic membrane, and large cytoplasmic inclusions of the n protein. to determine whether one of these two major rv proteins (g and n ...200312970438
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