Publications

targeting human glioblastoma cells: comparison of nine viruses with oncolytic potential.	brain tumors classified as glioblastomas have proven refractory to treatment and generally result in death within a year of diagnosis. we used seven in vitro tests and one in vivo trial to compare the efficacy of nine different viruses for targeting human glioblastoma. green fluorescent protein (gfp)-expressing vesicular stomatitis (vsv), sindbis virus, pseudorabies virus (prv), adeno-associated virus (aav), and minute virus of mice i-strain (mvmi) and mvmp all infected glioblastoma cells. mouse ...	2005	15857987
induction of antigen-specific immune responses against malignant brain tumors by intramuscular injection of sindbis dna encoding gp100 and il-18.	we constructed psin-sv40-hdv-sv40pa, an improved sindbis dna expression vector, and evaluated the potential of this vector system for brain tumor therapy. we investigated whether immunizing mice with xenogeneic dna encoding human gp100 and mouse il-18 would enhance the antitumor responses. to study the immune mechanisms involved in tumor regression, we examined tumor growth in b16-gp100-implanted brain tumor models using t-cell subset-depleted and ifn-gamma-neutralized mice. hugp100/mil-18 vacci ...	2005	15869409
association of signr1 with tlr4-md-2 enhances signal transduction by recognition of lps in gram-negative bacteria.	signr1, a member of a new family of mouse c-type lectins, is expressed at high levels in macrophages (mphi) within the splenic marginal zone, lymph node medulla, and in some strains, in peritoneal cavity. we previously reported that signr1 captures gram-negative bacteria, such as escherichia coli and salmonella typhimurium, as well as candida albicans. we have now investigated the precise ligands and innate responses that involve signr1. the interaction of signr1 with fitc-dextran and e. coli wa ...	2005	15908446
properties of sindbis virus vectors produced with a chimeric split helper system.	we have evaluated a chimeric, two-component sindbis virus packaging system. as expected, use of this combination of two modified helper rna species prevented formation of infection competent sindbis viruses as analyzed by serial passaging. we observed, however, that vectors produced using this method were able to spread in bhk cell cultures and formed clusters of transgene positive cells that did not display cytopathic effects for up to 3 days post-transduction. formation of spreading sindbis vi ...	2005	15870906
early arthritis and infection.	to summarize the recent literature on the association of infection with early arthritis, and to discuss the possible role of such infections with respect to the development of chronic rheumatic complications.	2005	15956840
clinical and laboratory manifestations of sindbis virus infection: prospective study, finland, 2002-2003.	sindbis virus (sinv) is widespread in europe, africa, australia, and asia, but clinical infection occurs as epidemics in a few geographically restricted areas. we recently proved, by virus isolation from patients, that sinv is the causative agent of pogosta disease, a mosquito-borne rash-arthritis occurring as larger epidemics every seventh year in finland. altogether, 86 patients with serologically verified sinv infection were recruited to the present study during the 2002 outbreak. we now desc ...	2005	15871114
persistent expression of factor viii in vivo following nonprimate lentiviral gene transfer.	hemophilia a is a clinically important coagulation disorder caused by the lack or abnormality of plasma coagulation factor viii (fviii). gene transfer of the fviii cdna to hepatocytes using lentiviral vectors is a potential therapeutic approach. we investigated the efficacy of feline immunodeficiency virus (fiv)-based vectors in targeting hepatocytes and correcting fviii deficiency in a hemophilia a mouse model. several viral envelope glycoproteins were screened for efficient fiv vector pseudoty ...	2005	15886327
long-range rna-rna interactions circularize the dengue virus genome.	secondary and tertiary rna structures present in viral rna genomes play essential regulatory roles during translation, rna replication, and assembly of new viral particles. in the case of flaviviruses, rna-rna interactions between the 5' and 3' ends of the genome have been proposed to be required for rna replication. we found that two rna elements present at the ends of the dengue virus genome interact in vitro with high affinity. visualization of individual molecules by atomic force microscopy ...	2005	15890901
castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo.	previous studies have suggested that alpha-glucosidase inhibitors such as castanospermine and deoxynojirimycin inhibit dengue virus type 1 infection by disrupting the folding of the structural proteins prm and e, a step crucial to viral secretion. we extend these studies by evaluating the inhibitory activity of castanospermine against a panel of clinically important flaviviruses including all four serotypes of dengue virus, yellow fever virus, and west nile virus. using in vitro assays we demons ...	2005	15994763
no signalling decodes frequency of neuronal activity and generates synapse-specific plasticity in mouse cerebellum.	nitric oxide (no) is an intercellular messenger regulating neuronal functions. to visualize no signalling in the brain, we generated a novel fluorescent no indicator, which consists of the heme-binding region (hbr) of soluble guanylyl cyclase and the green fluorescent protein. the indicator (hbr-gfp) was expressed in the purkinje cells of the mouse cerebellum and we imaged no signals in acute cerebellar slices upon parallel fibre (pf) activation with a train of burst stimulations (bs, each bs co ...	2005	15919714
respiratory syncytial virus nonstructural proteins ns1 and ns2 mediate inhibition of stat2 expression and alpha/beta interferon responsiveness.	respiratory syncytial virus (rsv) subverts the antiviral interferon (ifn) response, but the mechanism for this evasion was unclear. here we show that rsv preferentially inhibits ifn-alpha/beta signaling by expression of viral ns1 and ns2. thus, rsv infection or expression of recombinant ns1 and ns2 in epithelial host cells causes a marked decrease in stat2 levels and the consequent downstream ifn-alpha/beta response. similarly, ns1/ns2-deficient rsv no longer decreases stat2 levels or ifn respon ...	2005	15994826
the 5'-terminal region of the aichi virus genome encodes cis-acting replication elements required for positive- and negative-strand rna synthesis.	aichi virus is a member of the family picornaviridae. it has already been shown that three stem-loop structures (sl-a, sl-b, and sl-c, from the 5' end) formed at the 5' end of the genome are critical elements for viral rna replication. in this study, we further characterized the 5'-terminal cis-acting replication elements. we found that an additional structural element, a pseudoknot structure, is formed through base-pairing interaction between the loop segment of sl-b (nucleotides [nt] 57 to 60) ...	2005	15890931
complement activation is required for induction of a protective antibody response against west nile virus infection.	infection with west nile virus (wnv) causes a severe infection of the central nervous system (cns) with higher levels of morbidity and mortality in the elderly and the immunocompromised. experiments with mice have begun to define how the innate and adaptive immune responses function to limit infection. here, we demonstrate that the complement system, a major component of innate immunity, controls wnv infection in vitro primarily in an antibody-dependent manner by neutralizing virus particles in ...	2005	15919902
noncytopathic replication of venezuelan equine encephalitis virus and eastern equine encephalitis virus replicons in mammalian cells.	venezuelan equine encephalitis (vee) and eastern equine encephalitis (eee) viruses are important, naturally emerging zoonotic viruses. they are significant human and equine pathogens which still pose a serious public health threat. both vee and eee cause chronic infection in mosquitoes and persistent or chronic infection in mosquito-derived cell lines. in contrast, vertebrate hosts infected with either virus develop an acute infection with high-titer viremia and encephalitis, followed by host de ...	2005	15919912
indoleamine 2,3-dioxygenase mediates cell type-specific anti-measles virus activity of gamma interferon.	gamma interferon (ifn-gamma) has been shown to be increased in sera from patients with acute measles and after vaccination, to exhibit protective functions in brains of patients with subacute sclerosing panencephalitis, and to mediate a noncytolytic clearance of measles virus (mv) from rodent brains. in order to reveal a possible intracellular antiviral activity in the absence of antigen presentation and cytotoxic t cells, we investigated ifn-gamma-induced effects on mv replication in various ti ...	2005	15919929
inhibition of flavivirus infections by antisense oligomers specifically suppressing viral translation and rna replication.	rna elements within flavivirus genomes are potential targets for antiviral therapy. a panel of phosphorodiamidate morpholino oligomers (pmos), whose sequences are complementary to rna elements located in the 5'- and 3'-termini of the west nile (wn) virus genome, were designed to anneal to important cis-acting elements and potentially to inhibit wn infection. a novel arg-rich peptide was conjugated to each pmo for efficient cellular delivery. these pmos exhibited various degrees of antiviral acti ...	2005	15795246
requirements at the 3' end of the sindbis virus genome for efficient synthesis of minus-strand rna.	the 3'-untranslated region of the sindbis virus genome is 0.3 kb in length with a 19-nucleotide conserved sequence element (3' cse) immediately preceding the 3'-poly(a) tail. the 3' cse and poly(a) tail have been assumed to constitute the core promoter for minus-strand rna synthesis during genome replication; however, their involvement in this process has not been formally demonstrated. utilizing both in vitro and in vivo analyses, we have examined the role of these elements in the initiation of ...	2005	15795249
loss of interferon regulatory factor 3 in cells infected with classical swine fever virus involves the n-terminal protease, npro.	we show that cells infected with the pestivirus classical swine fever virus (csfv) fail to produce alpha/beta interferon not only following treatment with double-stranded rna but also after superinfection with a heterologous virus, the alphavirus sindbis virus, a virus shown to normally induce interferon. we investigated whether the inhibition of interferon synthesis by csfv involved a block in interferon regulatory factor 3 (irf3) activity. cells infected with csfv exhibited a lack of transloca ...	2005	15890962
design, synthesis, and evaluation of dioxane-based antiviral agents targeted against the sindbis virus capsid protein.	dioxane-based antiviral agents targeted to the hydrophobic binding pocket of sindbis virus capsid protein were designed by computer graphics molecular modeling and synthesized. virus production using sin-ires-luc and capsid assembly were monitored to evaluate antiviral activity. a compound with a three-carbon linker chain connecting two dioxane moieties inhibited virus production by 50% at a concentration of 40 microm, while (r)-hydroxymethyldioxane inhibited virus production by 50% at a concent ...	2005	15927464
rubella virus capsid protein modulation of viral genomic and subgenomic rna synthesis.	the ratio of the subgenomic (sg) to genome rna synthesized by rubella virus (rub) replicons expressing the green fluorescent protein reporter gene (rubrep/gfp) is substantially higher than the ratio of these species synthesized by rub (4.3 for rubrep/gfp vs. 1.3-1.4 for rub). it was hypothesized that this modulation of the viral rna synthesis was by one of the virus structural protein genes and it was found that introduction of the capsid (c) protein gene into the replicons as an in-frame fusion ...	2005	15907967
reversible acid-induced inactivation of the membrane fusion protein of semliki forest virus.	previously, it has been shown that the exposure of semliki forest virus (sfv) to a mildly acidic environment induces a rapid and complete loss of the ability of the virus to bind and fuse to target membranes added subsequently. in the present study, incubation of sfv at low ph followed by a specific reneutralization step resulted in a partial reversion of this loss of viral fusion capacity, as assessed in a liposomal model system. also, the ability of the viral e1 fusion protein to undergo lipos ...	2005	15919953
a family of mammalian e3 ubiquitin ligases that contain the ubr box motif and recognize n-degrons.	a subset of proteins targeted by the n-end rule pathway bear degradation signals called n-degrons, whose determinants include destabilizing n-terminal residues. our previous work identified mouse ubr1 and ubr2 as e3 ubiquitin ligases that recognize n-degrons. such e3s are called n-recognins. we report here that while double-mutant ubr1(-/-) ubr2(-/-) mice die as early embryos, the rescued ubr1(-/-) ubr2(-/-) fibroblasts still retain the n-end rule pathway, albeit of lower activity than that of w ...	2005	16055722
targeting sindbis virus-based vectors to fc receptor-positive cell types.	some viruses display enhanced infection for fc receptor (fcr)-positive cell types when complexed with virus-specific immunoglobulin (ig). this process has been termed antibody-dependent enhancement of viral infection (ade). we reasoned that the mechanism of ade could be exploited and adapted to target alphavirus-based vectors to fcr-positive cell types. towards this goal, recombinant sindbis viruses were constructed that express 1 to 4 immunoglobulin-binding domains of protein l (ppl) as n-termi ...	2005	15922395
california serogroup gc (g1) glycoprotein is the principal determinant of ph-dependent cell fusion and entry.	members of the california serogroup of orthobunyaviruses, particularly la crosse (lac) and tahyna (tah) viruses, are significant human pathogens in areas where their mosquito vectors are endemic. previous studies using wild-type lac and tah181/57, a highly neurovirulent strain with low neuroinvasiveness (janssen, r., gonzalez-scarano, f., nathanson, n., 1984. mechanisms of bunyavirus virulence. comparative pathogenesis of a virulent strain of la crosse and an avirulent strain of tahyna virus. la ...	2005	15923017
the use of gene silencing to study the role of dopa decarboxylase in mosquito melanization reactions.	mosquito melanization involves hydroxylation of tyrosine to dopa, which then is oxidized to dopaquinone by phenoloxidase, or decarboxylated to dopamine by dopa decarboxlase (ddc). an armigeres subalbatus cdna encoding ddc was cloned and real-time pcr analysis revealed increased transcripts in blood-fed and microfilariae (mf)-inoculated mosquitoes. a double subgenomic sindbis virus was used to silence ddc and assess its role in melanization of mf. ddc transcription and activity were significantly ...	2005	15926892
altering the tropism of lentiviral vectors through pseudotyping.	the host range of retroviral vectors including lentiviral vectors can be expanded or altered by a process known as pseudotyping. pseudotyped lentiviral vectors consist of vector particles bearing glycoproteins (gps) derived from other enveloped viruses. such particles possess the tropism of the virus from which the gp was derived. for example, to exploit the natural neural tropism of rabies virus, vectors designed to target the central nervous system have been pseudotyped using rabies virus-deri ...	2005	16101513
variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus.	eastern equine encephalitis virus (eeev) causes human encephalitis in north america (na), but in south america (sa) it has rarely been associated with human disease, suggesting that sa strains are less virulent. to evaluate the hypothesis that this virulence difference is due to a greater ability of na strains to evade innate immunity, we compared replication of na and sa strains in vero cells pretreated with interferon (ifn). human ifn-alpha, -beta, and -gamma generally exhibited less effect on ...	2005	16103182
rapid functional cloning of cell adhesion molecules.		2004	15597539
the zinc finger antiviral protein directly binds to specific viral mrnas through the ccch zinc finger motifs.	the zinc finger antiviral protein (zap) is a recently isolated host antiviral factor. it specifically inhibits the replication of moloney murine leukemia virus (mlv) and sindbis virus (sin) by preventing the accumulation of viral rna in the cytoplasm. for this report, we mapped the viral sequences that are sensitive to zap inhibition. the viral sequences were cloned into a luciferase reporter and analyzed for the ability to mediate zap-dependent destabilization of the reporter. the sensitive seq ...	2004	15542630
sindbis viruses and other alphaviruses as cause of human arthritic disease.	amongst the arthritis-causing arboviruses, i.e. those spread by insects, the alphavirus group is of special interest. these viruses occasionally cause vast outbreaks, such as o'nyong-nyong in africa in 1959. in fennoscandia, sindbis-related ockelbo, pogosta, or karelian fever viruses have been found to cause significant morbidity. the major symptoms in addition to joint inflammation are fever, fatigue, headache and rash. the joint symptoms may persist for weeks, even months. the diagnosis is bas ...	2004	15554947
two amino acid mutations in the capsid protein of type 2 porcine circovirus (pcv2) enhanced pcv2 replication in vitro and attenuated the virus in vivo.	porcine circovirus type 2 (pcv2) is the primary causative agent of postweaning multisystemic wasting syndrome (pmws) in pigs. to identify potential genetic determinants for virulence and replication, we serially passaged a pcv2 isolate 120 times in pk-15 cells. the viruses harvested at virus passages 1 (vp1) and 120 (vp120) were biologically, genetically, and experimentally characterized. the pcv2 vp120 virus replicated in pk-15 cells to a titer similar to that of the pk-15 cell line-derived non ...	2004	15564454
aedes aegypti salivary gland extracts modulate anti-viral and th1/th2 cytokine responses to sindbis virus infection.	vector-borne viruses are naturally transmitted when a vector salivates during feeding on a vertebrate host. most laboratory studies of infection disregard the role that the vector plays in the pathogenesis of the virus. in this study, intradermal inoculations of aedes aegypti salivary gland extract (sge) and sindbis virus (sinv) were used to investigate the effect of mosquito feeding on the vertebrate immune response to infection with an arthropod-borne virus. murine cytokine expression in the s ...	2004	15671753
a conserved histidine in the ij loop of the semliki forest virus e1 protein plays an important role in membrane fusion.	the enveloped alphavirus semliki forest virus (sfv) infects cells via a low ph-triggered membrane fusion reaction mediated by the e1 protein. e1 is a class ii fusion protein that contains the hydrophobic fusion peptide loop and converts to a stable homotrimer during the fusion reaction. intriguingly, the fusion loop is closely associated with a loop connecting the i and j beta-strands. this ij loop plays a role in the cholesterol dependence of membrane fusion and is specifically susceptible to p ...	2004	15564465
regulation of hcn channel surface expression by a novel c-terminal protein-protein interaction.	hyperpolarization-activated cation currents (i(h)) are carried by channels encoded by a family of four genes (hcn1-4) that are differentially expressed within the brain in specific cellular and subcellular compartments. hcn1 shows a high level of expression in apical dendrites of cortical pyramidal neurons and in presynaptic terminals of cerebellar basket cells, structures with a high density of i(h). expression of i(h) is also regulated by neuronal activity. to isolate proteins that may control ...	2004	15564593
alphaviruses and their derived vectors as anti-tumor agents.	the alphaviruses semliki forest virus (sfv) and sindbis virus have recently been developed as prototype anti-cancer agents. these are rna-containing enveloped viruses that code for only 9 proteins of unique sequence. the standard recombinant sfv vector system consists of suicide particles containing recombinant rna. in addition, alphavirus vectors capable of limited multiplication in the host are also being developed. several strategies are being adopted to construct prototype sfv vectors for ca ...	2004	15578917
trans-packaged west nile virus-like particles: infectious properties in vitro and in infected mosquito vectors.	a trans-packaging system for west nile virus (wnv) subgenomic replicon rnas (reprnas), deleted for the structural coding region, was developed. wnv reprnas were efficiently encapsidated by the wnv c/prm/e structural proteins expressed in trans from replication-competent, noncytopathic sindbis virus-derived rnas. infectious virus-like particles (vlps) were produced in titers of up to 10(9) infectious units/ml. wnv vlps established a single round of infection in a variety of different cell lines w ...	2004	15479801
cd209l (l-sign) is a receptor for severe acute respiratory syndrome coronavirus.	angiotensin-converting enzyme 2 (ace2) is a receptor for sars-cov, the novel coronavirus that causes severe acute respiratory syndrome [li, w. moore, m. j., vasilieva, n., sui, j., wong, s. k., berne, m. a., somasundaran, m., sullivan, j. l., luzuriaga, k., greenough, t. c., et al. (2003) nature 426, 450-454]. we have identified a different human cellular glycoprotein that can serve as an alternative receptor for sars-cov. a human lung cdna library in vesicular stomatitis virus g pseudotyped ret ...	2004	15496474
expression of antiapoptotic genes bcl-xl and ced-9 in tomato enhances tolerance to viral-induced necrosis and abiotic stress.	d satellite rna (satrna) is a strain of cucumber mosaic virus (cmv) satrna that induces an epidemic lethal disease in tomato. no natural resistance or tolerance has ever been found. previously, we demonstrated the involvement of programmed cell death in disease development. here, transgenic tomato plants expressing animal antiapoptotic genes bcl-xl and ced-9 were generated through agrobacterium-mediated transformation. high expression of bcl-xl or ced-9 affected plant growth and seed development ...	2004	15505199
analysis of adaptive mutations in kunjin virus replicon rna reveals a novel role for the flavivirus nonstructural protein ns2a in inhibition of beta interferon promoter-driven transcription.	the establishment of persistent noncytopathic replication by replicon rnas of a number of positive-strand rna viruses usually leads to generation of adaptive mutations in nonstructural genes. some of these adaptive mutations (e.g., in hepatitis c virus) increase the ability of rna replication to resist the antiviral action of alpha/beta interferon (ifn-alpha/beta); others (e.g., in sindbis virus) may also lead to more efficient ifn production. using puromycin-selectable kunjin virus (kun) replic ...	2004	15507609
cross talk between metabotropic and ionotropic glutamate receptor-mediated signaling in parallel fiber-induced inositol 1,4,5-trisphosphate production in cerebellar purkinje cells.	in many excitatory glutamatergic synapses, both ionotropic glutamate receptors (iglurs) and metabotropic glutamate receptors (mglurs) are closely distributed on the postsynaptic membrane. however, the functional significance of the close distribution of the two types of glutamate receptors has not been fully clarified. in this study, we examined the functional interaction between iglur and mglur at parallel fiber (pf)--> purkinje cell synapses in the generation of inositol 1,4,5-trisphosphate (i ...	2004	15509738
retinoid x receptor regulates nur77/tr3-dependent apoptosis [corrected] by modulating its nuclear export and mitochondrial targeting.	retinoid x receptor (rxr) plays a central role in the regulation of intracellular receptor signaling pathways by acting as a ubiquitous heterodimerization partner of many nuclear receptors, including the orphan receptor nur77 (also known as tr3 [corrected] or ngfi-b), which translocates from the nucleus to mitochondria, where it interacts with bcl-2 to induce apoptosis. here, we report that rxralpha is required for nuclear export and mitochondrial targeting of nur77 through their unique heterodi ...	2004	15509776
preferential targeting of vesicular stomatitis virus to breast cancer cells.	vesicular stomatitis virus (vsv) is a candidate for development for cancer therapy. we created a recombinant replicating vsv (rrvsv) with an altered surface protein that targeted preferentially to breast cancer cells. the rrvsv genome contained a single glycoprotein (gp) gene derived from sindbis virus. this gene expressed a chimeric sindbis e2 binding gp and the native sindbis e1 fusion gp. the chimeric e2 binding gp, called sindbis-sca-erbb2, was modified to reduce its native binding function ...	2004	15527831
role of isg15 protease ubp43 (usp18) in innate immunity to viral infection.	innate immune responses provide the host with an early protection barrier against infectious agents, including viruses, and help shape the nature and quality of the subsequent adaptive immune responses of the host. expression of isg15 (ucrp), a ubiquitin-like protein, and protein isgylation are highly increased upon viral infection. we have identified ubp43 (usp18) as an isg15 deconjugating protease. protein isgylation is enhanced in cells deficient in ubp43 (ref. 6). here we have examined the r ...	2004	15531891
transgenic mice expressing the nucleoprotein of borna disease virus in either neurons or astrocytes: decreased susceptibility to homotypic infection and disease.	the nucleoprotein (n) of borna disease virus (bdv) is the major target of the disease-inducing antiviral cd8 t-cell response in the central nervous system of mice. we established two transgenic mouse lines which express bdv-n in either neurons (neuro-n) or astrocytes (astro-n). despite strong transgene expression, neurological disease or gross behavioral abnormalities were not observed in these animals. when neuro-n mice were infected as adults, replication of bdv was severely impaired and was r ...	2004	15016883
a peptide from autoantigen la blocks poliovirus and hepatitis c virus cap-independent translation and reveals a single tyrosine critical for la rna binding and translation stimulation.	la, a 52-kda autoantigen in patients with systemic lupus erythematosus, was one of the first cellular proteins identified to interact with viral internal ribosome entry site (ires) elements and stimulate poliovirus (pv) and hepatitis c virus (hcv) ires-mediated translation. previous results from our laboratory have shown that a small, yeast rna (irna) could selectively inhibit pv and hcv ires-mediated translation by sequestering the la protein. here we have identified an 18-amino-acid-long seque ...	2004	15016896
rna interference, arthropod-borne viruses, and mosquitoes.	rna interference (rnai) probably functions as an antiviral mechanism in most eukaryotic organisms. variations in the activity of this antiviral pathway in mosquitoes could explain, in part, why some mosquitoes are competent vectors of medically important, arthropod-borne viruses (arboviruses) and others are not. there are three lines of evidence that show the rnai pathway exists in aedes species that transmit arboviruses. the first is that recombinant sindbis viruses expressing a rna fragment fr ...	2004	15068882
synthesis and antiviral evaluation of benzimidazoles, quinoxalines and indoles from dehydroabietic acid.	several heterocycles, such as benzimidazoles, quinoxalines and indoles incorporated into a hydrophenanthrene and naphthalene skeleton, were synthesised from two useful ortho-bromonitro precursors derived from dehydroabietic acid: methyl 12-bromo-13-nitro-deisopropyldehydroabietate and methyl 12-bromo-13,14-dinitro-deisopropyldehydroabietate. the new heterocycles were evaluated for their activity in vitro against several rna and dna viruses.	2004	14697775
borna disease virus multiplication in mouse organotypic slice cultures is site-specifically inhibited by gamma interferon but not by interleukin-12.	borna disease virus (bdv) induces a nonpurulent cd4- and cd8-t-cell-dependent meningoencephalitis in susceptible animals. upon intracerebral infection, bdv replicates in the mouse central nervous system (cns), but only a few mouse strains develop neurological disorder. the antiviral t cells appear to suppress bdv replication by a noncytolytic mechanism. since bdv does not replicate in standard mouse cell cultures, the putative role of gamma interferon (ifn-gamma) in virus control could not be te ...	2004	14722276
attenuation of dengue virus infection by adeno-associated virus-mediated sirna delivery.	background: the need for safe and effective treatment of dengue virus (den), a class a agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. an effective vaccine for den is not yet available. in this study the possibility of attenuating den infection using adeno-associated virus (aav)-encoded short interfering rnas (sirna) was examined in vero cells and human dendritic cells (dcs). methods: a cassette encoding sirna targeted to a 3' untranslated s ...	2004	15301687
attenuation of sindbis virus variants incorporating uncleaved pe2 glycoprotein is correlated with attachment to cell-surface heparan sulfate.	sindbis virus virions incorporating uncleaved precursor envelope protein pe2 bind efficiently to cell-surface heparan sulfate (hs) because the furin cleavage site (a consensus hs-binding domain) is retained in the mature virus particle. however, they are essentially nonviable. resuscitating mutations selected in the e3 or e2 protein preserve the pe2 noncleaving phenotype and hs binding, but facilitate fusion, and thereby restore wild-type infectivity on cultured cells. here, we have demonstrated ...	2004	15063111
phototoxicity against tumor cells and sindbis virus by an octahedral rhodium bisbipyridyl complex and evidence for the genome as a target in viral photoinactivation.	an octahedral rhodium complex (cis-dichloro(dipyrido[3,2a-2',3'c]phenazine)(1,10-phenanthroline)rhodium(iii) chloride; dppzphen) has been prepared that can penetrate tumor cell membranes and the sindbis viral capsid. the compound is phototoxic to these entities when irradiated with uva light. model studies with calf thymus and supercoiled plasmid dna indicate that the complex can both bind with, and nick, nucleic acid. analysis of sindbis virus, following irradiation with the metal complex, conf ...	2004	15310216
apoptosis is essential for the increased efficacy of alphaviral replicase-based dna vaccines.	alphaviral replicons can increase the efficacy and immunogenicity of naked nucleic acid vaccines. to study the impact of apoptosis on this increased effectiveness, we co-delivered an anti-apoptotic gene (bcl-x(l)) with the melanocyte/melanoma differentiation antigen trp-1. although cells co-transfected with bcl-x(l) lived longer, produced more antigen and elicited increased antibody production in vivo, co-delivery of pro-survival bcl-x(l) with antigen significantly reduced the ability of the rep ...	2004	15063579
the human membrane cofactor cd46 is a receptor for species b adenovirus serotype 3.	many human adenovirus (ad) serotypes use the coxsackie b virus-ad receptor (car). recently, cd46 was suggested to be a receptor of species b ad serotype 11 (ad11), ad14, ad16, ad21, ad35, and ad50. using sindbis virus-mediated cdna library expression, we identify here the membrane cofactor protein cd46 as a surface receptor of species b ad3. all four major cd46 transcripts and one minor cd46 transcript expressed in nucleated human cells were isolated. rodent bhk cells stably expressing the bc1 f ...	2004	15078926
receptor-dependent coronavirus infection of dendritic cells.	in several mammalian species, including humans, coronavirus infection can modulate the host immune response. we show a potential role of dendritic cells (dc) in murine coronavirus-induced immune modulation and pathogenesis by demonstrating that the jaw sii dc line and primary dc from balb/c mice and p/p mice with reduced expression of the murine coronavirus receptor, murine ceacam1a, are susceptible to murine coronavirus infection by a receptor-dependent pathway.	2004	15113927
human immunodeficiency virus type 1 envelope glycoproteins that lack cytoplasmic domain cysteines: impact on association with membrane lipid rafts and incorporation onto budding virus particles.	the human immunodeficiency virus type 1 (hiv-1) envelope comprises a surface gp120 and a transmembrane gp41. the cytoplasmic domain of gp41 contains cysteine residues (c764 and c837) which are targets for palmitoylation and were reported to be required for envelope association with lipid rafts and assembly on budding virions (i. rousso, m. b. mixon, b. k. chen, and p. s. kim, proc. natl. acad. sci. usa 97:13523-13525, 2000). several infectious hiv-1 clones contain envelopes that have no gp41 cyt ...	2004	15113929
processing of a pestivirus protein by a cellular protease specific for light chain 3 of microtubule-associated proteins.	the genome of the cytopathogenic (cp) bovine viral diarrhea virus (bvdv) jacp contains a cellular insertion coding for light chain 3 (lc3) of microtubule-associated proteins, the mammalian homologue of yeast aut7p/apg8p. the cellular insertion induces cp bvdv-specific processing of the viral polyprotein by a cellular cysteine protease homologous to the known yeast protease aut2p/apg4p. three candidate bovine protease genes were identified on the basis of the sequence similarity of their products ...	2004	15140988
independent functions of hsp90 in neurotransmitter release and in the continuous synaptic cycling of ampa receptors.	the delivery of neurotransmitter receptors into synapses is essential for synaptic function and plasticity. in particular, ampa-type glutamate receptors (ampa receptors) reach excitatory synapses according to two distinct routes: a regulated pathway, which operates transiently during synaptic plasticity, and a constitutive pathway, which maintains synaptic function under conditions of basal transmission. however, the specific mechanisms that distinguish these two trafficking pathways are essenti ...	2004	15152036
mcp-1 and ccr2 contribute to non-lymphocyte-mediated brain disease induced by fr98 polytropic retrovirus infection in mice: role for astrocytes in retroviral neuropathogenesis.	virus infection of the central nervous system (cns) often results in chemokine upregulation. although often associated with lymphocyte recruitment, increased chemokine expression is also associated with non-lymphocyte-mediated cns disease. in these instances, the effect of chemokine upregulation on neurological disease is unclear. in vitro, several chemokines including monocyte chemotactic protein 1 (mcp-1) protect neurons from apoptosis. therefore, in vivo, chemokine upregulation may be a prote ...	2004	15163738
regulation of semliki forest virus rna replication: a model for the control of alphavirus pathogenesis in invertebrate hosts.	alphavirus nonstructural proteins are translated as a polyprotein that is ultimately cleaved into four mature proteins called nsp1, nsp2, nsp3, and nsp4 from their order in the polyprotein. the role of this nonstructural polyprotein, of cleavage intermediates, and of mature proteins in synthesis of semliki forest virus (sfv) rna has been studied using mutants unable to cleave one or more of the sites in the nonstructural polyprotein or that had the arginine sense codon between nsp3 and nsp4 chan ...	2004	15165827
neuronal apoptosis pathways in sindbis virus encephalitis.	sindbis virus infects neurons of the brain and spinal cord leading to neuronal apoptosis and encephalitis in mice. during postnatal development, neurons of mice remain susceptible to infection but become refractory to sv-induced programmed cell death. failure to undergo programmed cell death results in a persistent infection. however, some neurovirulent strains of sindbis virus overcome the age-dependent protective function in neurons, leading to enhanced apoptotic cell death in the central nerv ...	2004	15171608
identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions.	sympathetic premotor neurons directly control sympathetic preganglionic neurons (spns) in the intermediolateral cell column (iml) of the thoracic spinal cord, and many of these premotor neurons are localized in the medulla oblongata. the rostral ventrolateral medulla contains premotor neurons controlling the cardiovascular conditions, whereas rostral medullary raphe regions are a candidate source of sympathetic premotor neurons for thermoregulatory functions. here, we show that these medullary r ...	2004	15190110
regulation of synaptic strength and ampa receptor subunit composition by pick1.	pick1 (protein interacting with c kinase-1) regulates the surface expression of the ampa receptor (ampar) glur2 subunit, however, the functional consequences of this interaction are not well understood. previous work has suggested that pick1 promotes the internalization of ampars. however, we found that when pick1 is virally expressed in the ca1 region of hippocampal slices, it causes an increase in ampar-mediated epsc amplitude. this effect is associated with increased ampar rectification and s ...	2004	15190111
identification of the amino acid sequence in sindbis virus nsp4 that binds to the promoter for the synthesis of the subgenomic rna.	a gel mobility-shift assay was used to demonstrate the binding of the sindbis virus transcriptase to the promoter for the synthesis of subgenomic (sg) rna. the assay made use of a p15 fraction (the cell fraction that is pelleted at 15,000 x g) from cells infected with recombinant vaccinia virions expressing various sindbis virus nonstructural proteins (nsps) and a (32)p-labeled 24-mer oligoribonucleotide representing the minimal sequence with sg promoter activity. by itself, nsp4, the viral rna- ...	2004	15197279
endemic venezuelan equine encephalitis in northern peru.	since venezuelan equine encephalitis virus (veev) was isolated in peru in 1942, >70 isolates have been obtained from mosquitoes, humans, and sylvatic mammals primarily in the amazon region. to investigate genetic relationships among the peru veev isolates and between the peru isolates and other veev strains, a fragment of the pe2 gene was amplified and analyzed by single-stranded conformation polymorphism. representatives of seven genotypes underwent sequencing and phylogenetic analysis. the res ...	2004	15200823
causative agent of pogosta disease isolated from blood and skin lesions.	pogosta disease is a mosquito-borne viral disease in finland, which is clinically manifested by rash and arthritis; larger outbreaks occur in 7-year intervals. the causative agent of the disease has been suspected of being closely related to sindbis virus (sinv). we isolated sinv from five patients with acute pogosta disease during an outbreak in fall 2002 in finland. one virus strain was recovered from a whole blood sample and four other strains from skin lesions. the etiology of pogosta diseas ...	2004	15200824
antigenic and genetic typing of whataroa viruses in australia.	we recently characterized three novel alphaviruses isolated from mosquitoes captured in new south wales, australia. initial cross-neutralization studies revealed antigenic similarity to the sindbis virus (sinv)-like whataroa virus (whav), heretofore found only in new zealand. nucleotide sequence analysis showed that the whav-like viruses shared >99% nucleotide sequence similarity with each other, and 96-97% similarity with prototype whav. enzyme-linked immunosorbent assay reactions of a panel of ...	2004	15381803
conformational changes in sindbis virions resulting from exposure to low ph and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion.	alphaviruses have the ability to induce cell-cell fusion after exposure to acid ph. this observation has served as an article of proof that these membrane-containing viruses infect cells by fusion of the virus membrane with a host cell membrane upon exposure to acid ph after incorporation into a cell endosome. we have investigated the requirements for the induction of virus-mediated, low ph-induced cell-cell fusion and cell-virus fusion. we have correlated the ph requirements for this process to ...	2004	15207623
doxorubicin and paclitaxel enhance the antitumor efficacy of vaccines directed against her 2/neu in a murine mammary carcinoma model.	the purpose of the present study was to determine whether cytotoxic chemotherapeutic agents administered prior to immunotherapy with gene vaccines could augment the efficacy of the vaccines.	2004	15217493
bad is a pro-survival factor prior to activation of its pro-apoptotic function.	the mammalian bad protein belongs to the bh3-only subgroup of the bcl-2 family. in contrast to its known pro-apoptotic function, we found that endogenous and overexpressed bad(l) can inhibit cell death in neurons and other cell types. several mechanisms regulate the conversion of bad from an anti-death to a pro-death factor, including alternative splicing that produces the n-terminally truncated bad(s). in addition, caspases convert bad(l) into a pro-death fragment that resembles the short splic ...	2004	15231831
input- and subunit-specific ampa receptor trafficking underlying long-term potentiation at hippocampal ca3 synapses.	hippocampal ca3 pyramidal neurons receive synaptic inputs from both mossy fibres (mfs) and associational fibres (afs). long-term potentiation (ltp) at these synapses differs in its induction sites and n-methyl-d-aspartate receptor (nmdar) dependence. most evidence favours the presynaptic and postsynaptic mechanisms for induction of mf ltp and af ltp, respectively. this implies that molecular and functional properties differ between mf and af synapses at both presynaptic and postsynaptic sites. i ...	2004	15245483
evolutionary transition toward defective rnas that are infectious by complementation.	passage of foot-and-mouth disease virus (fmdv) in cell culture resulted in the generation of defective rnas that were infectious by complementation. deletions (of nucleotides 417, 999, and 1017) mapped in the l proteinase and capsid protein-coding regions. cell killing followed two-hit kinetics, defective genomes were encapsidated into separate viral particles, and individual viral plaques contained defective genomes with no detectable standard fmdv rna. infection in the absence of standard fmdv ...	2004	15479809
the pdz domain of pick1 differentially accepts protein kinase c-alpha and glur2 as interacting ligands.	the c terminus (ct) of protein kinase c-alpha (pkcalpha) has a type i pdz binding motif, whereas glur2 has a type ii pdz binding motif. both motifs are recognized by the pdz domain of protein interacting with protein kinase c (pick1), and pick1-pkcalpha-controlled phosphorylation regulates the synaptic expression and function of glur2. here, we show that a specific mutation within the carboxylate-binding loop of the pdz domain of pick1 (k27e; pick1-ke) results in a loss of interaction with glur2 ...	2004	15247289
rna encoding the mpt83 antigen induces protective immune responses against mycobacterium tuberculosis infection.	we have previously demonstrated that vaccination of mice with plasmid dna vectors expressing immunodominant mycobacterial genes induced cellular immune responses and significant protection against challenge with mycobacterium tuberculosis. we demonstrate here, using in vitro-synthesized rna, that vaccination with dna or rna constructs expressing the m. tuberculosis mpt83 antigen are capable of inducing specific humoral and t-cell immune responses and confer modest but significant protection agai ...	2004	15501761
cytokine-mediated downregulation of coxsackievirus-adenovirus receptor in endothelial cells.	endothelial cells have the ability to change their complement of cell surface proteins in response to inflammatory cytokines. we hypothesized that the expression of the coxsackievirus-adenovirus receptor (car), a viral receptor and putative cell-cell adhesion molecule, may be altered during the response of endothelial cells to inflammation. to test this hypothesis, we evaluated car protein and mrna levels in human umbilical vein endothelial cells after they were exposed to tumor necrosis factor ...	2004	15254176
role of cd8+ t cells in control of west nile virus infection.	infection with west nile virus (wnv) causes fatal encephalitis more frequently in immunocompromised humans than in those with a healthy immune system. although a complete understanding of this increased risk remains unclear, experiments with mice have begun to define how different components of the adaptive and innate immune response function to limit infection. previously, we demonstrated that components of humoral immunity, particularly immunoglobulin m (igm) and igg, have critical roles in pr ...	2004	15254203
serotype-specific entry of dengue virus into liver cells: identification of the 37-kilodalton/67-kilodalton high-affinity laminin receptor as a dengue virus serotype 1 receptor.	dengue virus, the causative agent of dengue fever, dengue shock syndrome, and dengue hemorrhagic fever, infects susceptible cells by initially binding to a receptor(s) located on the host cell surface. evidence to date suggests that receptor usage may be cell and serotype specific, and this study sought to identify dengue virus serotype 1 binding proteins on the surface of liver cells, a known target organ. by using a virus overlay protein binding assay (vopba), in both nondenaturing and denatur ...	2004	15507651
the nucleoprotein is required for efficient coronavirus genome replication.	the construction of a set of transmissible gastroenteritis coronavirus (tgev)-derived replicons as bacterial artificial chromosomes is reported. these replicons were generated by sequential deletion of nonessential genes for virus replication, using a modified tgev full-length cdna clone containing unique restriction sites between each pair of consecutive genes. efficient activity of tgev replicons was associated with the presence of the nucleoprotein provided either in cis or in trans. tgev rep ...	2004	15507657
ebna2 is required for protection of latently epstein-barr virus-infected b cells against specific apoptotic stimuli.	in addition to functioning as a transcriptional transactivator, epstein-barr virus ebna2 interacts with nur77 to protect against nur77-mediated apoptosis. estrogen-regulated ebna2 in ereb2-5 cells was replaced by either ebna2 or ebna2 with a deletion of conserved region 4 (ebna2deltacr4). both ebna2-converted and ebna2deltacr4-converted ereb2-5 cells grew in the absence of estrogen and expressed lmp1. treatment with tumor necrosis factor alpha did not induce apoptosis of ebna2- or ebna2deltacr4- ...	2004	15507659
inactivation of west nile virus, vaccinia virus and viral surrogates for relevant and emergent viral pathogens in plasma-derived products.	human plasma is the source of a wide variety of therapeutic proteins, yet it is also a potential source of viral contamination. recent outbreaks of emergent viral pathogens, such as west nile virus, and the use of live vaccinia virus as a vaccine have prompted a reassessment of the viral safety of plasma-derived products. the purpose of this study was to evaluate the efficacy of current viral inactivation methods for west nile and vaccinia viruses and to reassess the use of model viruses to pred ...	2004	15260817
rapid preparative purification of west nile and sindbis virus pcr products utilizing a microbore anion-exchange column.	analysis and purification of specific pcr products from pcr reactions can be problematic due to several issues relating to amplification and low product yield. the use of hplc as a preparative tool in pcr product analysis is common but has not replaced traditional electrophoretic techniques for purifying dna to be used in subsequent experiments. gel purification of pcr products can result in a net loss greater than 50% of the starting dna amount. thus, this method of recovery can become the limi ...	2004	15288956
[antibodies against mosquito-born viruses in human population of an area of central bohemia affected by the flood of 2002].	in the central-bohemian area affected by the flood of 2002, 497 residents were screened for antibodies against the mosquito-borne viruses tahyna (tahv), west nile (wnv), sindbis (sinv) and batai (batv; syn. calovo) using the haemagglutination-inhibition (hit) and plaque-reduction neutralization (prnt) tests. blood samples were collected in september 2002 when the mosquito populations showed the maximum density following the flood. antibodies against tahv (16.5% persons in prnt, 14.9% in hit), si ...	2004	15524269
subcellular localization and calcium and ph requirements for proteolytic processing of the hendra virus fusion protein.	proteolytic cleavage of the hendra virus fusion (f) protein results in the formation of disulfide-linked f1 and f2 subunits, with cleavage occurring after residue k109 in the sequence gdvk/l. this unusual cleavage site and efficient propagation of hendra virus in a furin-deficient cell line indicate that the hendra f protein is not cleaved by furin, the protease responsible for proteolytic activation of many viral fusion proteins. to identify the subcellular site of hendra f processing, vero cel ...	2004	15308711
effects of ras and rap1 on electrical excitability of differentiated ng108-15 cells.	effects of two small g-proteins, rap1 and ras, on the sodium channel activity in ng108-15 cells were studied using sindbis virus-mediated gene transfer. when an activated rap1a mutant (rap1-12v, the activated mutant of rap1 carrying glycine to valine substitution at codon 12) or a dominant-negative h-ras mutant (ras-17n, carrying serine to asparagine substitution at codon 17) was expressed in differentiated ng108-15 cells, the proportion of cells generating action potential decreased and the amp ...	2004	15312909
viral-induced spinal motor neuron death is non-cell-autonomous and involves glutamate excitotoxicity.	neuroadapted sindbis virus (nsv) is a neurotropic virus capable of inducing the death of spinal motor neurons in mice and rats. in this study we investigated the mechanisms that underlie nsv-induced motor neuron death. we found that many degenerating spinal motor neurons were not infected directly with nsv, suggesting that bystander cell death occurs. an excitotoxic mechanism was confirmed when blockade of calcium-permeable ampa receptors attenuated motor neuron death both in vitro and in vivo. ...	2004	15329404
intranasal immunization with inactivated influenza virus enhances immune responses to coadministered simian-human immunodeficiency virus-like particle antigens.	intranasal immunization with inactivated influenza virus vaccine can provide protective immunity, whereas many other antigens are less effective when used for mucosal immunization. to determine whether influenza virus could enhance immune responses to an antigen coadministered to a mucosal surface, we studied the intranasal immunization of mice with a mixture of simian-human immunodeficiency virus (shiv) virus-like particles (vlps) and inactivated influenza virus. compared to mice immunized with ...	2004	15331695
coexpression of hepatitis c virus e1 and e2 chimeric envelope glycoproteins displays separable ligand sensitivity and increases pseudotype infectious titer.	we have previously reported that a pseudotype virus generated by reconstitution of hepatitis c virus (hcv) chimeric envelope glycoprotein e1-g or e2-g on the surface of a temperature-sensitive mutant of vesicular stomatitis virus (vsvts045) interacts independently with mammalian cells to initiate infection. here, we examined whether coexpression of both of the envelope glycoproteins on pseudotype particles would augment virus infectivity and/or alter the functional properties of the individual s ...	2004	15542636
proteomics computational analyses suggest that the carboxyl terminal glycoproteins of bunyaviruses are class ii viral fusion protein (beta-penetrenes).	the bunyaviridae family of enveloped rna viruses includes five genuses, orthobunyaviruses, hantaviruses, phleboviruses, nairoviruses and tospoviruses. it has not been determined which bunyavirus protein mediates virion:cell membrane fusion. class ii viral fusion proteins (beta-penetrenes), encoded by members of the alphaviridae and flaviviridae, are comprised of three antiparallel beta sheet domains with an internal fusion peptide located at the end of domain ii. proteomics computational analyse ...	2004	15544707
a mutant of sindbis virus which is able to replicate in cells with reduced ctp makes a replicase/transcriptase with a decreased km for ctp.	we reported earlier the isolation and characterization of a sindbis virus mutant, sv(pzf), that can grow in mosquito cells treated with pyrazofurin (pzf), a compound that interferes with pyrimidine biosynthesis (y. h. lin, p. yadav, r. ravatn, and v. stollar, virology 272:61-71, 2000; y. h. lin, h. a. simmonds, and v. stollar, virology 292:78-86, 2002). three amino acid changes in nsp4, the viral rna polymerase, were required to produce this phenotype. we now describe a mutant of sindbis virus, ...	2004	15331697
discrimination among rhinovirus serotypes for a variant icam-1 receptor molecule.	intercellular adhesion molecule 1 (icam-1) is the cellular receptor for the major group of human rhinovirus serotypes, including human rhinovirus 14 (hrv14) and hrv16. a naturally occurring variant of icam-1, icam-1kilifi, has altered binding characteristics with respect to different hrv serotypes. hrv14 binds to icam-1 only transiently at physiological temperatures but forms a stable complex with icam-1kilifi. conversely, hrv16 forms a stable complex with icam-1 but does not bind to icam-1kilif ...	2004	15331736
the immunoglobulin family member dendrite arborization and synapse maturation 1 (dasm1) controls excitatory synapse maturation.	in the developing mammalian brain, a large fraction of excitatory synapses initially contain only n-methyl-d-aspartate receptor and thus are "silent" at the resting membrane potential. as development progresses, synapses acquire alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (ampa-rs). although this maturation of excitatory synapses has been well characterized, the molecular basis for this developmental change is not known. here, we report that dendrite arborization and synap ...	2004	15340156
protein kinase c-alpha activity is required for respiratory syncytial virus fusion to human bronchial epithelial cells.	respiratory syncytial virus (rsv) infection activates protein kinase c (pkc), but the precise pkc isoform(s) involved and its role(s) remain to be elucidated. on the basis of the activation kinetics of different signaling pathways and the effect of various pkc inhibitors, it was reasoned that pkc activation is important in the early stages of rsv infection, especially rsv fusion and/or replication. herein, the role of pkc-alpha during the early stages of rsv infection in normal human bronchial e ...	2004	15564481
biological diversity versus risk for mosquito nuisance and disease transmission in constructed wetlands in southern sweden.	in southern sweden, many wetlands have been constructed, and maintaining or increasing biological diversity is often included in the aims. some wetlands are constructed near human settlements, thus raising the problem of wetlands being associated with mosquitoes (diptera: culicidae). increased biodiversity (including mosquito diversity) is considered desirable, whereas mosquito nuisance from a human point of view is not. adult mosquito abundance, diversity and species assemblages of constructed ...	2004	15347393
sindbis viral-mediated expression of egfp-dopamine d1 receptors in situ with real-time two-photon microscopic detection.	dopamine d1 receptors (d1drs) mediate a major component of dopaminergic neurotransmission, and alterations in their synaptic and subcellular distribution may underlie a variety of neurological diseases. in order to monitor d1dr localization in real time, we subcloned a sindbis virus containing an enhanced-gfp coding region inserted at the c-terminal region of a dopamine d1 receptor (egfp-d1dr). two-photon excitation of expressed egfp-d1drs was monitored in a variety of viable neural preparations ...	2004	15351518
rna interference acts as a natural antiviral response to o'nyong-nyong virus (alphavirus; togaviridae) infection of anopheles gambiae.	rna interference (rnai) is triggered in eukaryotic organisms by double-stranded rna (dsrna), and it destroys any mrna that has sequence identity with the dsrna trigger. the rnai pathway in anopheles gambiae can be silenced by transfecting cells with dsrna derived from exon sequence of the a. gambiae argonaute2 (agago2) gene. we hypothesized that rnai may also act as an antagonist to alphavirus replication in a. gambiae because rna viruses form dsrna during replication. silencing agago2 expressio ...	2004	15583140
zap is a crm1-dependent nucleocytoplasmic shuttling protein.	the zinc finger antiviral protein (zap) is a recently isolated host antiviral factor. it specifically inhibits the replication of moloney murine leukemia virus (mmlv) and sindbis virus (sin) by preventing the accumulation of viral rna in the cytoplasm. in this report, we demonstrate that zap is predominantly localized in the cytoplasm at steady state but shuttles between the nucleus and the cytoplasm in a crm1-dependent manner. two nuclear localization sequences (nls) and one nuclear export sequ ...	2004	15358138
human immunodeficiency virus type 1 gag-specific mucosal immunity after oral immunization with papillomavirus pseudoviruses encoding gag.	mucosal surfaces are the primary portals for human immunodeficiency virus (hiv) transmission. because systemic immunization, in general, does not induce effective mucosal immune responses, a mucosal hiv vaccine is urgently needed. for this study, we developed papillomavirus pseudoviruses that express hiv-1 gag. the pseudoviruses are synthetic, nonreplicating viruses, yet they can produce antigens for a long time in the immune system. here we show that oral immunization of mice by the use of papi ...	2004	15367590
structural properties of a multifunctional t-shaped rna domain that mediate efficient tomato bushy stunt virus rna replication.	in positive-strand rna viruses, 5' untranslated regions (5' utrs) mediate many essential viral processes, including genome replication. previously, we proposed that the 5'-terminal portion of the genomic leader sequence of tomato bushy stunt virus (tbsv) forms an rna structure containing a 3-helix junction, termed the t-shaped domain (tsd). in the present study, we have carried out structure-function analysis of the proposed tsd and have confirmed an important role for this domain in mediating e ...	2004	15367615
temporal modulation of an autoprotease is crucial for replication and pathogenicity of an rna virus.	pestiviruses belong to the family flaviviridae, and their genome is a single-stranded rna of positive polarity encoding one large polyprotein which is further processed into mature proteins. noncytopathogenic (noncp) strains of the pestivirus bovine viral diarrhea virus (bvdv) can establish persistent infection. in persistently infected animals, noncp bvdvs occasionally acquire mutations in viral nonstructural protein 2 (ns2) that give rise to cytopathogenic (cp) bvdv variants, and, eventually, ...	2004	15367643
gene therapy for malignant glioma using sindbis vectors expressing a fusogenic membrane glycoprotein.	malignant glioma has a dismal prognosis. it was previously shown that glioma cells are efficiently killed when they express a gene coding for a hyperfusogenic mutant of the gibbon ape leukemia virus envelope glycoprotein (galv.fus). however, production of viral vectors expressing galv.fus has proven problematic because the transgene is toxic to vector-producing cells of human origin. we reasoned that sindbis-virus-based vectors might be ideal for galv.fus gene transfer because high-titer stocks ...	2004	15368589
using sindbis viral vectors for specific detection and suppression of advanced ovarian cancer in animal models.	we studied the therapeutic value of sindbis vectors for advanced metastatic ovarian cancer by using two highly reproducible and clinically accurate mouse models: a scid xenograft model, established by i.p. inoculation of human es-2 ovarian cancer cells, and a syngenic c57bl/6 model, established by i.p. inoculation of mouse mosec ovarian cancer cells. we demonstrate through imaging, histologic, and molecular data that sindbis vectors systemically and specifically infect/detect and kill metastasiz ...	2004	15374985