PMID(sorted ascending)
profile of diane e. griffin. 200516087864
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 ...200516101513
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 ...200516103182
enhancement of enveloped virus entry by phosphatidylserine.enveloped virus vectors are used in a wide variety of applications. we have discovered that treatment of cultured cells with phosphatidylserine (ps) liposomes can increase virus vector infection by up to 20-fold. this effect does not abrogate virus receptor requirements, is specific to ps compared to other phospholipids, and is limited to enveloped viruses. furthermore, the enhancement of infection does not occur through increases in virus receptor levels or virus binding, indicating that virus ...016103200
state-dependent ras signaling and ampa receptor trafficking.synaptic trafficking of ampa-rs, controlled by small gtpase ras signaling, plays a key role in synaptic plasticity. however, how ras signals synaptic ampa-r trafficking is unknown. here we show that low levels of ras activity stimulate extracellular signal-regulated kinase kinase (mek)-p42/44 mapk (extracellular signal-regulated kinase [erk]) signaling, whereas high levels of ras activity stimulate additional pi3 kinase (pi3k)-protein kinase b (pkb) signaling, each accounting for approximately 5 ...200516107614
local translation of rhoa regulates growth cone collapse.neuronal development requires highly coordinated regulation of the cytoskeleton within the developing axon. this dynamic regulation manifests itself in axonal branching, turning and pathfinding, presynaptic differentiation, and growth cone collapse and extension. semaphorin 3a (sema3a), a secreted guidance cue that primarily functions to repel axons from inappropriate targets, induces cytoskeletal rearrangements that result in growth cone collapse. these effects require intra-axonal messenger rn ...200516107849
identification of amino acids of sindbis virus e2 protein involved in targeting tumor metastases in vivo.previous studies conducted in our laboratory with sindbis viral vectors in animal models demonstrated excellent in vivo targeting of tumor cells and significant reduction of metastatic implant size. to explore the influence of sindbis strain on these factors, we constructed new plasmids from the wild-type ar-339 sindbis virus strain and compared their sequences. we found differences in the replicase and envelope proteins between jt, hrsp, and ar-339 sequences. we made chimeras combining both str ...200516109508
infection of dendritic cells by a gamma2-herpesvirus induces functional modulation.the murine gamma-herpesvirus-68 (gammahv68) establishes viral latency in dendritic cells (dcs). in the present study, we examined the specific consequences of dc infection by gammahv68, both in vivo and in vitro. ex vivo analysis of infected mice showed that the virus colonizes respiratory dcs very early after infection and that all subsets of splenic dcs analyzed are viral targets. we have developed and characterized an in vitro model of gammahv68 infection of dcs. using this model, we demonstr ...200516116213
hybrid sindbis/epstein-barr virus episomal expression vector for inducible production of proteins.alphavirus vectors are attractive as recombinant protein expression systems due to the high level of gene expression achieved. the combination of two mutations in the viral replicase, which render the replicase noncytopathic and temperature-sensitive, allowed the generation of a dna-based vector (cytts) that shows temperature inducible expression. this vector is of significant value for the production of toxic protein. however, like for other stable expression systems, tedious screening of indiv ...200516116794
quantification of different human alpha interferon subtypes and pegylated interferon activities by measuring mxa promoter activation.alpha interferons (alpha-ifns) are potent biologically active proteins synthesized and secreted by somatic cells during viral infection. quantification of alpha-ifn concentrations in biological samples is used for diagnosis. more recently, recombinant ifns have been used as antiviral, antiproliferative, and immunomodulatory therapeutic agents, and particularly for the treatment of chronic hepatitis c virus infection. for this purpose, ifn has recently been coupled to polyethylene glycol (peg) to ...200516127052
a novel ca2+ indicator protein using fret and calpain-sensitive, we report the properties of a fret-based calcium indicator protein. we constructed a tandem fusion protein, named f2c, of ecfp and eyfp combined with calpain-sensitive sequences of alpha-spectrin, with n-terminal palmitoylation signal of gap-43. it was previously reported that calpain cleaved a similar ecfp-eyfp fusion protein linked by a calpain-sensitive sequence of alpha-spectrin (fodrin). unexpectedly, f2c was not cleaved by calpain, but demonstrated properties of a ca(2+) indicator wh ...200516129417
pick1 is a calcium-sensor for nmda-induced ampa receptor trafficking.regulation of ampa receptor (ampar) trafficking results in changes in receptor number at the postsynaptic membrane, and hence modifications in synaptic strength, which are proposed to underlie learning and memory. nmda receptor-mediated postsynaptic ca2+ influx enhances ampar internalisation, but the molecular mechanisms that trigger such trafficking are not well understood. we investigated whether ampar-associated protein-protein interactions known to regulate receptor surface expression may be ...200516138078
kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal ca1 pyramidal neurones.a-type potassium channels regulate neuronal firing frequency and the back-propagation of action potentials (aps) into dendrites of hippocampal ca1 pyramidal neurones. recent molecular cloning studies have found several families of voltage-gated k(+) channel genes expressed in the mammalian brain. at present, information regarding the relationship between the protein products of these genes and the various neuronal functions performed by voltage-gated k(+) channels is lacking. here we used a comb ...200516141270
critical roles for both stat1-dependent and stat1-independent pathways in the control of primary dengue virus infection in mice.dengue virus (den), a flavivirus, causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, the most common mosquito-borne viral illnesses in humans worldwide. in this study, using stat1(-/-) mice bearing two different mutant stat1 alleles in the 129/sv/ev background, we demonstrate that ifnr-dependent control of primary den infection involves both stat1-dependent and stat1-independent mechanisms. the stat1 pathway is necessary for clearing the initial viral load, whereas the stat1 ...200516148142
antiviral silencing in animals.rna silencing or rna interference (rnai) refers to the small rna-guided gene silencing mechanism conserved in a wide range of eukaryotic organisms from plants to mammals. as part of this special issue on the biology, mechanisms and applications of rnai, here we review the recent advances on defining a role of rnai in the responses of invertebrate and vertebrate animals to virus infection. approximately 40 mirnas and 10 rnai suppressors encoded by diverse mammalian viruses have been identified. a ...200516154568
carbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins.defensins are peptides that protect the host against microorganisms. here we show that the theta-defensin retrocyclin 2 (rc2) inhibited influenza virus infection by blocking membrane fusion mediated by the viral hemagglutinin. rc2 was effective even after hemagglutinin attained a fusogenic conformation or had induced membrane hemifusion. rc2, a multivalent lectin, prevented hemagglutinin-mediated fusion by erecting a network of crosslinked and immobilized surface glycoproteins. rc2 also inhibite ...200516155572
both antigen optimization and lysosomal targeting are required for enhanced anti-tumour protective immunity in a human papillomavirus e7-expressing animal tumour model.dna immunization is a new approach for cancer immune therapy. in this study, we constructed human papillomavirus (hpv) 16 e7 expression vector cassettes and then compared the abilities of these constructs to induce antitumour protection. lysosome-targeted e7 antigens, and to a lesser degree signal sequence-conjugated and transmembrane region sequence-conjugated e7 antigens in a dna form, displayed tumour protection significantly higher than wild-type e7 antigens. this enhanced tumour protection ...200516162274
prime-boost vaccination with plasmid and adenovirus gene vaccines control her2/neu+ metastatic breast cancer in mice.once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for her2/neu. a vaccine targeting p185, the protein product of the her2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive her2/neu+ cells. the purpose of this study was to determine the effectiveness of two gene vaccines targeting her2/neu in preventive and therapeutic tumor models.200516168101
evaluation of cis-acting elements in the rubella virus subgenomic rna that play a role in its translation.the subgenomic (sg) mrna of rubella virus (rub) contains the structural protein open reading frame (sp-orf) that is translated to produce the three virion structural proteins: capsid (c) and glycoproteins e2 and e1. rub expression vectors have been developed that express heterologous genes from the sg rna, including replicons which replace the sp-orf with a heterologous gene, and these expression vectors are candidate vaccine vectors. in the related alphaviruses, translational enhancing elements ...200616172842
adp-ribose-1"-monophosphatase: a conserved coronavirus enzyme that is dispensable for viral replication in tissue culture.replication of the approximately 30-kb plus-strand rna genome of coronaviruses and synthesis of an extensive set of subgenome-length rnas are mediated by the replicase-transcriptase, a membrane-bound protein complex containing several cellular proteins and up to 16 viral nonstructural proteins (nsps) with multiple enzymatic activities, including protease, polymerase, helicase, methyltransferase, and rnase activities. to get further insight into the replicase gene-encoded functions, we characteri ...200516188975
virus infection switches tlr-3-positive human neurons to become strong producers of beta study the capacity of human neurons to mount innate immunity responses to viral infections, we infected cells of a human postmitotic neuron-derivative cell line, nt2-n, with rabies virus (rabv) and herpes simplex type 1 (hsv-1). changes in neuronal gene expression were analyzed by use of affymetrix microarrays. applying a twofold cutoff, rabv increased the transcription of 228 genes, and hsv-1 increased the transcription of 263 genes. the most striking difference between the two infections co ...200516188991
autophagy in cell death: an innocent convict?the visualization of autophagosomes in dying cells has led to the belief that autophagy is a nonapoptotic form of programmed cell death. this concept has now been evaluated using cells and organisms deficient in autophagy genes. most evidence indicates that, at least in cells with intact apoptotic machinery, autophagy is primarily a pro-survival rather than a pro-death mechanism. this review summarizes the evidence linking autophagy to cell survival and cell death, the complex interplay between ...016200202
a surface groove essential for viral bcl-2 function during chronic infection in vivo.antiapoptotic bcl-2 family proteins inhibit apoptosis in cultured cells by binding bh3 domains of proapoptotic bcl-2 family members via a hydrophobic bh3 binding groove on the protein surface. we investigated the physiological importance of the bh3 binding groove of an antiapoptotic bcl-2 protein in mammals in vivo by analyzing a viral bcl-2 family protein. we show that the gamma-herpesvirus 68 (gammahv68) bcl-2 family protein (gammahv68 v-bcl-2), which is known to inhibit apoptosis in cultured ...200516201011
sindbis virus induces transport processes and alters expression of innate immunity pathway genes in the midgut of the disease vector, aedes aegypti.the midgut of hematophagous insects is the initial site of infection by arthropod-borne viruses (arboviruses) and plays a crucial role in vector competence. to further understand processes that occur in the midgut in response to infection by an arbovirus, dna microarrays were used to analyze gene expression changes following infection by the alphavirus, sindbis (mre16 malaysian strain). midgut transcription profiles from mosquitoes fed blood containing 10(8)pfu/ml of virus were compared with tho ...200516203210
domain iii from class ii fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion.alphaviruses and flaviviruses infect cells through low ph-dependent membrane fusion reactions mediated by their structurally similar viral fusion proteins. during fusion, these class ii viral fusion proteins trimerize and refold to form hairpin-like structures, with the domain iii and stem regions folded back toward the target membrane-inserted fusion peptides. we demonstrate that exogenous domain iii can function as a dominant-negative inhibitor of alphavirus and flavivirus membrane fusion and ...200516216925
biological transmission of arboviruses: reexamination of and new insights into components, mechanisms, and unique traits as well as their evolutionary trends.among animal viruses, arboviruses are unique in that they depend on arthropod vectors for transmission. field research and laboratory investigations related to the three components of this unique mode of transmission, virus, vector, and vertebrate host, have produced an enormous amount of valuable information that may be found in numerous publications. however, despite many reviews on specific viruses, diseases, or interests, a systematic approach to organizing the available information on all f ...016223950
ceramide-enriched membrane domains.cellular activation involves the re-organization of receptor molecules and the intracellular signalosom in the cell membrane. recent studies indicate that specialized domains of the cell membrane, termed rafts, are central for the spatial organization of receptors and signaling molecules. rafts are converted into larger membrane platforms by activity of the acid sphingomyelinase, which hydrolyses raft-sphingomyelin to ceramide. ceramide molecules spontaneously associate to form ceramide-enriched ...200516226325
alpha/beta interferon protects against lethal west nile virus infection by restricting cellular tropism and enhancing neuronal survival.west nile virus (wnv) is a mosquito-borne flavivirus that is neurotropic in humans, birds, and other animals. while adaptive immunity plays an important role in preventing wnv spread to the central nervous system (cns), little is known about how alpha/beta interferon (ifn-alpha/beta) protects against peripheral and cns infection. in this study, we examine the virulence and tropism of wnv in ifn-alpha/beta receptor-deficient (ifn- alpha/betar-/-) mice and primary neuronal cultures. ifn-alpha/beta ...200516227257
cd8 t cells require gamma interferon to clear borna disease virus from the brain and prevent immune system-mediated neuronal damage.borna disease virus (bdv) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain mrl. disease does not result from the virus-induced destruction of infected neurons. rather, it is mediated by h-2(k)-restricted antiviral cd8 t cells that recognize a peptide derived from the bdv nucleoprotein n. persistent bdv infection in mice is not spontaneously cleared. we report here that n-specific vaccination can protect wild-type mrl mice but not mutant mrl ...200516227271
influenza virus hemagglutinin (h3 subtype) requires palmitoylation of its cytoplasmic tail for assembly: m1 proteins of two subtypes differ in their ability to support assembly.the influenza a virus hemagglutinin (ha) transmembrane domain boundary region and the cytoplasmic tail contain three cysteines (residues 555, 562, and 565 for the h3 ha subtype) that are highly conserved among the 16 ha subtypes and which are each modified by the covalent addition of palmitic acid. previous analysis of the role of these conserved cysteine residues led to differing data, suggesting either no role for ha palmitoylation or an important role for ha palmitoylation. to reexamine the r ...200516227287
human immunodeficiency virus type 1 vpr interacts with antiapoptotic mitochondrial protein hax-1.human immunodeficiency virus type 1 viral protein r (vpr) is required for viral pathogenesis and has been implicated in t-cell apoptosis through its activation of caspase 3 and caspase 9 and perturbation of mitochondrial membrane potential. to understand better vpr-mitochondria interaction, we report here the identification of antiapoptotic mitochondrial protein hax-1 as a novel vpr target. we show that vpr and hax-1 physically associate with each other. overexpression of vpr in cells dislocates ...200516227293
aberrant cortical neurogenesis in a pediatric neuroaids model: neurotrophic effects of growth study the effects of hiv-1 and feline immunodeficiency virus (fiv) on neural stem cell viability, together with the neurotrophic properties of growth hormone (gh) in models of pediatric neuroaids.200516227785
biology and application of alphaviruses in gene therapy.the broad host cell range and high expression levels of transgenes are features that have made alphaviruses attractive for gene expression studies and gene therapy applications. particularly, semliki forest virus vectors have been applied for large-scale production of recombinant membrane proteins for drug screening purposes and structural biology studies. the high preference of expression in neuronal cells has led to many applications of alphavirus vectors in neuroscience. studies on localizati ...200516231060
the efficient packaging of venezuelan equine encephalitis virus-specific rnas into viral particles is determined by nsp1-3 synthesis.alphaviruses are regarded as attractive systems for expression of heterologous genes and development of recombinant vaccines. venezuelan equine encephalitis virus (vee)-based vectors are particularly promising because of their specificity to lymphoid tissues and strong resistance to interferon. to improve understanding of the vee genome packaging and optimize application of this virus as a vector, we analyzed in more detail the mechanism of packaging of the vee-specific rnas. the presence of the ...200616239019
vaccination with a sindbis virus-based dna vaccine expressing antigen 85b induces protective immunity against mycobacterium improve dna vaccination against mycobacterium tuberculosis, we evaluated the effectiveness of a sindbis virus-based dna construct expressing the tuberculosis antigen 85b (sin85b). the protective efficacy of sin85b was initially assessed by aerogenically challenging immunized c57bl/6 mice with virulent mycobacterium tuberculosis. at 1 and 7 months postinfection, the lung bacterial burdens were considerably reduced and the lung pathology was improved in vaccinated mice compared to naive control ...200516239577
fluorescent labeling of rat auditory brainstem circuits for synaptic and electrophysiological studies.we visualized neurons with fluorescent agents, both retrogradely and anterogradely, to identify the input and output neuronal pathways in the rat auditory system. output neurons of dorsal cochlear nucleus (dcn) were labeled retrogradely by injecting fluorescent microspheres into the inferior colliculus. electrical recordings were made from the labeled fusiform cells of dcn with the whole-cell patch-clamp recording technique in slice preparations. dii and sindbis virus expressing membrane-targete ...200616246426
stress-activated protein kinases are involved in coxsackievirus b3 viral progeny release.stress-activated protein kinases (sapks), consisting of c-jun n-terminal kinase (jnk) and p38 mitogen-activated protein kinase (p38 mapk), are activated upon various environmental stimuli, including viral infections. cellular survival and death signaling events following coxsackievirus b3 (cvb3) infection have been studied in relationship to viral replication, but the role of sapks has not been scrutinized. in this study, we found that the phosphorylation of jnk1/2 and p38 mapk was increased dur ...200516254323
identification of interferon-stimulated gene 15 as an antiviral molecule during sindbis virus infection in vivo.the innate immune response, and in particular the alpha/beta interferon (ifn-alpha/beta) system, plays a critical role in the control of viral infections. interferons alpha and beta exert their antiviral effects through the induction of hundreds of interferon-induced (or -stimulated) genes (isgs). while several of these isgs have characterized antiviral functions, their actions alone do not explain all of the effects mediated by ifn-alpha/beta. to identify additional ifn-induced antiviral molecu ...200516254333
alpha/beta interferons regulate murine gammaherpesvirus latent gene expression and reactivation from latency.alpha/beta interferon (ifn-alpha/beta) protects the host from virus infection by inhibition of lytic virus replication in infected cells and modulation of the antiviral cell-mediated immune response. to determine whether ifn-alpha/beta also modulates the virus-host interaction during latent virus infection, we infected mice lacking the ifn-alpha/beta receptor (ifn-alpha/betar(-/-)) and wild-type (wt; 129s2/svpas) mice with murine gammaherpesvirus 68 (gammahv68), a lymphotropic gamma-2-herpesviru ...200516254350
effect of alternating passage on adaptation of sindbis virus to vertebrate and invertebrate cells.mosquito-borne alphaviruses, which replicate alternately and obligately in mosquitoes and vertebrates, appear to experience lower rates of evolution than do many rna viruses that replicate solely in vertebrates. this genetic stability is hypothesized to result from the alternating host cycle, which constrains evolution by imposing compromise fitness solutions in each host. to test this hypothesis, sindbis virus was passaged serially, either in one cell type to eliminate host alteration or altern ...200516254360
[the ecology and prevalence of arboviruses on the territory of the saratov region].the territorial spread of tahyna, batai, sindbis, west nile fever and crimean-congo hemorrhagic fever viruses throughout the saratov region in 1998 - 2000 was analyzed. the characteristics of the epizootic activity of the natural foci of these arboviruses in different landscape zones (temperate forest-steppes, steppes and semi-deserts) were calculated. the species composition of small mammals, the natural reservoirs of the causative agents of arbovirus infections, was determined.200516279530
endocytosis and a low-ph step are required for productive entry of equine infectious anemia virus.recently, it has become evident that entry of some retroviruses into host cells is dependent upon a vesicle-localized, low-ph step. the entry mechanism of equine infectious anemia virus (eiav) has yet to be examined. here, we demonstrate that wild-type strains of eiav require a low-ph step for productive entry. lysosomotropic agents that inhibit the acidification of internal vesicles inhibited productive entry of eiav. the presence of ammonium chloride (30 mm), monensin (30 microm), or bafilomyc ...200516282447
receptor-mediated entry by equine infectious anemia virus utilizes a ph-dependent endocytic pathway.previous studies of human and nonhuman primate lentiviral entry mechanisms indicate a predominant use of ph-independent pathways, although more recent studies of human immunodeficiency virus type 1 entry appear to reveal the use of a low-ph-dependent entry pathway in certain target cells. to expand the characterization of the specificity of lentiviral entry mechanisms, we have in the current study examined the entry pathway of equine infectious anemia virus (eiav) during infection of its natural ...200516282448
the aauaaa motif of bamboo mosaic virus rna is involved in minus-strand rna synthesis and plus-strand rna polyadenylation.bamboo mosaic virus (bamv) has a single-stranded positive-sense rna genome with a 5'-cap structure and a 3' poly(a) tail. deleting the internal loop that contains the putative polyadenylation signal (aauaaa) in the 3' untranslated region (utr) of bamv genomic rna appeared to diminish coat protein accumulation to 2% (c. p. cheng and c. h. tsai, j. mol. biol. 288:555-565, 1999). to investigate the function of the aauaaa motif, mutations were introduced into an infectious bamv cdna at each residue ...200516282455
human parainfluenza virus type 4 is incapable of evading the interferon-induced antiviral effect.the v proteins of some paramyxoviruses have developed the ability to efficiently inactivate stat protein function as a countermeasure for evading interferon (ifn) responses. human parainfluenza virus type 4 (hpiv4) is one of the rubulaviruses, which are members of the family paramyxoviridae, and has a v protein with a highly conserved cysteine-rich domain that is the hallmark of paramyxovirus v proteins. in order to study the function of the hpiv4 v protein, we established hela cells expressing ...200516282476
the role of the 3' terminus of the sindbis virus genome in minus-strand initiation site selection.genome replication of plus-strand rna viruses begins with the generation of a minus-strand copy of the genome. minus-strand synthesis must initiate at or close to the 3' end of the genome and progress to processive elongation to yield the appropriate template for genomic rna synthesis. the sindbis virus genome possesses a 3' polyadenylate tail preceded by a 19 nucleotide conserved sequence element (3' cse). analyses of in vitro and in vivo synthesized minus-strand rna presented in this manuscrip ...200616297426
kinetic evaluation of photosensitivity in genetically engineered neurons expressing green algae light-gated channels.neurons become photosensitive by genetically introducing one of green algae-derived protein, channelrhodopsin-2 (chr2). here, we quantitatively investigated the rapidness of the light-gated current of chr2 expressed in pc12 cells using blue light-emitting diode (led) light. the light-gated current consists of two components, inactivating and non-inactivating. the magnitude of inactivating component was almost linearly related to the light intensity. the non-inactivating component showed a tenden ...200616298005
rare earth ions block the ion pores generated by the class ii fusion proteins of alphaviruses and allow analysis of the biological functions of these pores.recently, class ii fusion proteins have been identified on the surface of alpha- and flaviviruses. these proteins have two functions besides membrane fusion: they generate an isometric lattice on the viral surface and they form ion-permeable pores at low ph. an attempt was made to identify inhibitors for the ion pores generated by the fusion proteins of the alphaviruses semliki forest virus and sindbis virus. these pores can be detected and analysed in three situations: (i) in the target membran ...200516298976
insight into a conserved lifestyle: protein-carbohydrate adhesion strategies of vector-borne pathogens. 200516299269
functional and genetic analysis of coronavirus replicase-transcriptase proteins.the coronavirus replicase-transcriptase complex is an assembly of viral and cellular proteins that mediate the synthesis of genome and subgenome-sized mrnas in the virus-infected cell. here, we report a genetic and functional analysis of 19 temperature-sensitive (ts) mutants of murine hepatitis virus mhv-a59 that are unable to synthesize viral rna when the infection is initiated and maintained at the non-permissive temperature. both classical and biochemical complementation analysis leads us to ...200516341254
translation of sindbis virus 26s mrna does not require intact eukariotic initiation factor 4g.the infection of baby hamster kidney (bhk) cells by sindbis virus gives rise to a drastic inhibition of cellular translation, while under these conditions the synthesis of viral structural proteins directed by the subgenomic 26s mrna takes place efficiently. here, the requirement for intact initiation factor eif4g for the translation of this subgenomic mrna has been examined. to this end, sv replicons that contain the protease of human immunodeficiency virus type 1 (hiv-1) or the poliovirus 2a(p ...200616343528
cd8+ t cells require perforin to clear west nile virus from infected neurons.injury to neurons after west nile virus (wnv) infection is believed to occur because of viral and host immune-mediated effects. previously, we demonstrated that cd8+ t cells are required for the resolution of wnv infection in the central nervous system (cns). cd8+ t cells can control infection by producing antiviral cytokines (e.g., gamma interferon or tumor necrosis factor alpha) or by triggering death of infected cells through perforin- or fas ligand-dependent pathways. here, we directly evalu ...200616352536
identification and characterization of a penaeus monodon lymphoid cell-expressed receptor for the yellow head virus.the yellow head virus is a positive-sense, single-stranded rna virus that causes significant mortality in farmed penaeid shrimp. this study sought to isolate and characterize the receptor protein used by the virus to gain entry into penaeus monodon oka (lymphoid) organ cells, a primary target of yellow head virus infections. virus overlay protein binding assay on oka organ membrane preparations identified a 65-kda protein, and antibodies raised against this protein inhibited virus entry in prima ...200616352551
viral transgenesis of embryonic cell cultures from the freshwater microcrustacean daphnia.the aim of this study was to determine whether a recombinant vesicular stomatitis virus (vsv) vector encoding a transgene could be used to infect and express a foreign gene in embryonic primary cell cultures derived from the freshwater microcrustacean daphnia, the most widely used ecotoxicological model organism. to facilitate the evaluation of gene transfer, a reproducible method for establishing primary cultures from daphnia embryonic tissues was developed. within 24 hr after infection, transg ...200616358270
direct pyrogenic input from prostaglandin ep3 receptor-expressing preoptic neurons to the dorsomedial hypothalamus.fever is induced by a neuronal mechanism in the brain. prostaglandin (pg) e2 acts as a pyrogenic mediator in the preoptic area (poa) probably through the ep3 subtype of pge receptor expressed on gabaergic neurons, and this pge2 action triggers neuronal pathways for sympathetic thermogenesis in peripheral effector organs including brown adipose tissue (bat). to explore pyrogenic efferent pathways from the poa, we determined projection targets of ep3 receptor-expressing poa neurons with a special ...200516367780
reovirus variants selected for resistance to ammonium chloride have mutations in viral outer-capsid protein sigma3.mammalian reoviruses are internalized into cells by receptor-mediated endocytosis. within the endocytic compartment, the viral outer capsid undergoes acid-dependent proteolysis resulting in removal of the sigma3 protein and proteolytic cleavage of the mu1/mu1c protein. ammonium chloride (ac) is a weak base that blocks disassembly of reovirus virions by inhibiting acidification of intracellular vacuoles. to identify domains in reovirus proteins that influence ph-sensitive steps in viral disassemb ...200616378970
heparin-binding and patterns of virulence for two recombinant strains of sindbis virus.e2 is an important determinant of sindbis virus neurovirulence. increased heparan sulfate (hs) binding is associated with rapid clearance of viremia and usually with decreased virulence. however, substitution of histidine for arginine at e2-157 (r157h) or glutamate for lysine at e2-159 (k159e) produces viruses with decreases in heparin-sepharose binding and increases in viremia but different levels of binding to hs-expressing cells and virulence phenotypes in newborn cd-1 mice (byrnes, a.p., gri ...200616380143
ube1l and protein isgylation are not essential for alpha/beta interferon signaling.the expression of ubiquitin-like modifier isg15 and its conjugation to target proteins are highly induced by interferon (ifn) stimulation and during viral and bacterial infections. however, the biological significance of this modification has not been clearly understood. to investigate the function of protein modification by isg15, we generated a mouse model deficient in ube1l, an isg15-activating enzyme. ube1l-/- mice did not produce isg15 conjugates but expressed free isg15 normally. isgylatio ...200616382139
single and multiple deletions in the transmembrane domain of the sindbis virus e2 glycoprotein identify a region critical for normal virus growth.sindbis virus is composed of two nested t = 4 icosahedral protein shells containing 240 copies each of three structural proteins: e1, e2, and capsid in a 1:1:1 stoichiometric ratio. e2 is a 423 amino acid glycoprotein with a membrane spanning domain 26 amino acids in length and a 33 amino acid cytoplasmic endodomain. the interaction of the endodomain with the nucleocapsid is an essential step in virus maturation and directs the formation of the outer protein shell as envelopment occurs. a previo ...200616387341
classical nucleation theory of virus capsids.a fundamental step in the replication of a viral particle is the self-assembly of its rigid shell (capsid) from its constituent proteins. capsids play a vital role in genome replication and intercellular movement of viruses, and as such, understanding viral assembly has great potential in the development of new antiviral therapies and a systematic treatment of viral infection. in this article, we assume that nucleation is the underlying mechanism for self-assembly and combine the theoretical met ...200516387781
translational resistance of late alphavirus mrna to eif2alpha phosphorylation: a strategy to overcome the antiviral effect of protein kinase pkr.the double-stranded rna-dependent protein kinase (pkr) is one of the four mammalian kinases that phosphorylates the translation initiation factor 2alpha in response to virus infection. this kinase is induced by interferon and activated by double-stranded rna (dsrna). phosphorylation of eukaryotic initiation factor 2alpha (eif2alpha) blocks translation initiation of both cellular and viral mrna, inhibiting virus replication. to counteract this effect, most viruses express inhibitors that prevent ...200616391235
mapping the structure and function of the e1 and e2 glycoproteins in alphaviruses.the 9 a resolution cryo-electron microscopy map of sindbis virus presented here provides structural information on the polypeptide topology of the e2 protein, on the interactions between the e1 and e2 glycoproteins in the formation of a heterodimer, on the difference in conformation of the two types of trimeric spikes, on the interaction between the transmembrane helices of the e1 and e2 proteins, and on the conformational changes that occur when fusing with a host cell. the positions of various ...200616407066
anti-viral rna silencing: do we look like plants?the anti-viral function of rna silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. it appears that, whereas the anti-viral process seems to be similarly ...200616409629
jam-a-independent, antibody-mediated uptake of reovirus into cells leads to apoptosis.apoptosis plays a major role in the cytopathic effect induced by reovirus following infection of cultured cells and newborn mice. strain-specific differences in the capacity of reovirus to induce apoptosis segregate with the s1 and m2 gene segments, which encode attachment protein sigma1 and membrane penetration protein mu1, respectively. virus strains that bind to both junctional adhesion molecule-a (jam-a) and sialic acid are the most potent inducers of apoptosis. in addition to receptor bindi ...200616415003
palmitoylations on murine coronavirus spike proteins are essential for virion assembly and infectivity.coronavirus spike (s) proteins are palmitoylated at several cysteine residues clustered near their transmembrane-spanning domains. this is achieved by cellular palmitoyl acyltransferases (pats), which can modify newly synthesized s proteins before they are assembled into virion envelopes at the intermediate compartment of the exocytic pathway. to address the importance of these fatty acylations to coronavirus infection, we exposed infected cells to 2-bromopalmitate (2-bp), a specific pat inhibit ...200616415005
west nile virus discriminates between dc-sign and dc-signr for cellular attachment and infection.the c-type lectins dc-sign and dc-signr bind mannose-rich glycans with high affinity. in vitro, cells expressing these attachment factors efficiently capture, and are infected by, a diverse array of appropriately glycosylated pathogens, including dengue virus. in this study, we investigated whether these lectins could enhance cellular infection by west nile virus (wnv), a mosquito-borne flavivirus related to dengue virus. we discovered that dc-signr promoted wnv infection much more efficiently t ...200616415006
[detection of sindbis virus-specific nucleic acid with sybr green i real time pcr assay].to develop a rapid, specific and sensitive method for detecting sindbis virus (sinv) with sybr green i real time pcr.200516415993
dissection of a viral autoprotease elucidates a function of a cellular chaperone in proteolysis.replication of positive-strand rna viruses involves translation of polyproteins which are proteolytically processed into functional peptides. these maturation steps often involve virus-encoded autoproteases specialized in generating their own n or c termini. nonstructural protein 2 (ns2) of the pestivirus bovine viral diarrhea virus represents such an enzyme. bovine viral diarrhea virus ns2 creates in cis its own c terminus and thereby releases an essential viral replication factor. as a unique ...200616432213
time- and temperature-dependent activation of hepatitis c virus for low-ph-triggered entry.hepatitis c virus (hcv) is an important human pathogen associated with chronic liver disease. recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and infectious virus production have been developed. in this study, we used cell culture-produced infectious hcv to analyze the viral entry pathway into huh-7.5 cells. bafilomycin a1 and concanamycin a, inhibitors of vacuolar atpases, prevented hcv entry when they were present prior to infection and had mini ...200616439530
core protein of pestiviruses is processed at the c terminus by signal peptide peptidase.the core protein of pestiviruses is released from the polyprotein by viral and cellular proteinases. here we report on an additional intramembrane proteolytic step that generates the c terminus of the core protein. c-terminal processing of the core protein of classical swine fever virus (csfv) was blocked by the inhibitor (z-ll)(2)-ketone, which is specific for signal peptide peptidase (spp). the same effect was obtained by overexpression of the dominant-negative spp d(265)a mutant. the presence ...200616439547
structural characterization of the e2 glycoprotein from sindbis by lysine biotinylation and lc-ms/ms.sindbis is an alphavirus capable of infecting and replicating in both vertebrate and invertebrate hosts. mature sindbis virus particles consist of an inner capsid surrounded by a host-derived lipid bilayer, which in turn is surrounded by a protein shell consisting of the e1 and e2 glycoproteins. while a homolog of the e1 glycoprotein has been structurally characterized, the amount of structural data on the e2 glycoprotein is considerably less. in this study, the organization of the e2 glycoprote ...200616443253
rna secondary structure in the coding region of dengue virus type 2 directs translation start codon selection and is required for viral replication.dengue virus is a positive-strand rna virus and a member of the genus flavivirus, which includes west nile, yellow fever, and tick-borne encephalitis viruses. flavivirus genomes are translated as a single polyprotein that is subsequently cleaved into 10 proteins, the first of which is the viral capsid (c) protein. dengue virus type 2 (denv2) and other mosquito-borne flaviviruses initiate translation of c from a start codon in a suboptimal context and have multiple in-frame augs downstream. here, ...200616474125
a single amino acid substitution in the west nile virus nonstructural protein ns2a disables its ability to inhibit alpha/beta interferon induction and attenuates virus virulence in mice.alpha/beta interferons (ifn-alpha/beta) are key mediators of the innate immune response against viral infection. the ability of viruses to circumvent ifn-alpha/beta responses plays a crucial role in determining the outcome of infection. in a previous study using subgenomic replicons of the kunjin subtype of west nile virus (wnv(kun)), we demonstrated that the nonstructural protein ns2a is a major inhibitor of ifn-beta promoter-driven transcription and that a single amino acid substitution in ns2 ...200616474146
role of a conserved tripeptide in the endodomain of sindbis virus glycoprotein e2 in virus assembly and function.envelopment of sindbis virus (sv) at the plasma membrane begins with the interaction of the e2 glycoprotein endodomain with a hydrophobic cleft in the surface of the pre-assembled nucleocapsid. the driving force for this budding event is thought to reside in this virus type-specific association at the surface of the cell. the specific amino acids involved in this interaction have not been identified; however, it has been proposed that a conserved motif (tpy) at aa 398-400 in the e2 tail plays a ...200616476988
ampa receptor downscaling at the onset of alzheimer's disease pathology in double knockin is widely thought that alzheimer's disease (ad) begins as a malfunction of synapses, eventually leading to cognitive impairment and dementia. homeostatic synaptic scaling is a mechanism that could be crucial at the onset of ad but has not been examined experimentally. in this process, the synaptic strength of a neuron is modified so that the overall excitability of the cell is maintained. here, we investigate whether synaptic scaling mediated by l-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepro ...200616492745
functional analyses of gb virus b p13 protein: development of a recombinant gb virus b hepatitis virus with a p7 virus b (gbv-b), which infects tamarins, is the virus most closely related to hepatitis c virus (hcv). hcv has a protein (p7) that is believed to form an ion channel. it is critical for viability. in vitro studies suggest that gbv-b has an analogous but larger protein (p13). we found that substitutions of the -1 and/or -3 residues of the putative cleavage sites (amino acid 613/614 and 732/733) abolished processing in vitro and rendered an infectious gbv-b clone nonviable in tamarins. internal ...200616492760
replication and clearance of venezuelan equine encephalitis virus from the brains of animals vaccinated with chimeric sin/vee viruses.venezuelan equine encephalitis virus (veev) is an important, naturally emerging zoonotic pathogen. recent outbreaks in venezuela and colombia in 1995, involving an estimated 100,000 human cases, indicate that veev still poses a serious public health threat. to develop a safe, efficient vaccine that protects against disease resulting from veev infection, we generated chimeric sindbis (sin) viruses expressing structural proteins of different strains of veev and analyzed their replication in vitro ...200616501087
a single codon in the nucleocapsid protein c terminus contributes to in vitro and in vivo fitness of edmonston measles virus.the major inducible 70-kda heat shock protein (hsp72) increases measles virus (mv) transcription and genome replication. this stimulatory effect is attributed to hsp72 interaction with two highly conserved hydrophobic domains in the nucleocapsid protein (n) c terminus of edmonston mv. these domains are known as box-2 and box-3. a single amino acid substitution in box-3 of edmonston mv (i.e., n522d) disrupts hsp72 binding. the prevalence of the n522d substitution in contemporary wild-type mv isol ...200616501099
rnase l plays a role in the antiviral response to west nile virus.alleles at the flv locus determine disease outcome after a flavivirus infection in mice. although comparable numbers of congenic resistant and susceptible mouse embryo fibroblasts (mefs) are infected by the flavivirus west nile virus (wnv), resistant mefs produce approximately 100- to 150-fold lower titers than susceptible ones and flavivirus titers in the brains of resistant and susceptible animals can differ by >10,000-fold. the flv locus was previously identified as the 2'-5' oligoadenylate s ...200616501108
identification of mutations causing temperature-sensitive defects in semliki forest virus rna synthesis.we have sequenced the nonstructural protein coding region of semliki forest virus temperature-sensitive (ts) mutant strains ts1, ts6, ts9, ts10, ts11, ts13, and ts14. in each case, the individual amino acid changes uncovered were transferred to the prototype strain background and thereby identified as the underlying cause of the altered rna synthesis phenotype. all mutations mapping to the protease domain of nonstructural protein nsp2 caused defects in nonstructural polyprotein processing and su ...200616501123
sindbis virus as a tool for quality control of viral inactivation of heated and chemically treated plasma-derived products.regulatory guidelines for production of plasma-derived products emphasize the need to document methods of viral inactivation and demonstrate the effectiveness of screening methods. therefore, it is important to evaluate the kinetics of such processes. togaviridae family virions may be considered as good tools for quality control of haemoderivatives, if they possess large amounts of cholesterol and saturated lipids and high structural lipid/protein ratio in their envelope composition, which give ...200616507321
high-dose gamma irradiation for soft tissue allografts: high margin of safety with biomechanical integrity.screening and processing methods currently in place have made the risk of bacterial and viral infections from allograft tissues extremely low. however, the development of a terminal sterilization method that does not adversely affect tissue function would provide an added safety to tissues for transplantation. we assessed whether high-dose gamma irradiation could be used as an effective terminal sterilization method for allografts without impairing the preimplantation mechanical integrity of the ...200616514624
a colorimetric assay for viral agents that produce cytopathic effects.many animal viruses produce cytopathic effects in their host cells during a productive infection. while some virus infections can be assayed by the production of plaques, many viruses, while producing cytotoxicity, do not easily form plaques, or do not form plaques at all. additionally, viruses within families such as the parvoviruses may have different preferred forms of titration making comparative virology difficult even among related groups. porcine parvovirus (ppv), canine parvovirus (cpv), ...200616516983
nonstructural protein of infectious bursal disease virus inhibits apoptosis at the early stage of virus infection.infectious bursal disease virus (ibdv), the causative agent of a highly contagious disease in chickens, carries a small nonstructural protein (ns). this protein has been implicated to play a role in the induction of apoptosis. in this study, we investigate the kinetics of viral replication during a single round of viral replication and examine the mechanism of ibdv-induced apoptosis. our results show that it is caspase dependent and activates caspases 3 and 9. nuclear factor kappa b (nf-kappab) ...200616537604
mutagenesis analysis of the nsp4 main proteinase reveals determinants of arterivirus replicase polyprotein autoprocessing.nonstructural protein 4 (nsp4; 204 amino acids) is the chymotrypsin-like serine main proteinase of the arterivirus equine arteritis virus (order nidovirales), which controls the maturation of the replicase complex. nsp4 includes a unique c-terminal domain (ctd) connected to the catalytic two-beta-barrel structure by the poorly conserved residues 155 and 156. this dipeptide might be part of a hinge region (hr) that facilitates interdomain movements and thereby regulates (in time and space) autopr ...200616537610
porcine circovirus 2 uses heparan sulfate and chondroitin sulfate b glycosaminoglycans as receptors for its attachment to host cells.monocyte/macrophage lineage cells are target cells in vivo for porcine circovirus 2 (pcv2) replication. the porcine monocytic cell line 3d4/31 supports pcv2 replication in vitro, and attachment and internalization kinetics of pcv2 have been established in these cells. however, pcv2 receptors remain unknown. glycosaminoglycans (gag) are used by several viruses as receptors. the present study examined the role of gag in attachment and infection of pcv2. heparin, heparan sulfate (hs), chondroitin s ...200616537616
rab22a regulates the sorting of transferrin to recycling endosomes.rab22a is a member of the rab family of small gtpases that localizes in the endocytic pathway. in cho cells, expression of canine rab22a (crab22a) causes a dramatic enlargement of early endocytic compartments. we wondered whether transferrin recycling is altered in these cells. expression of the wild-type protein and a gtp hydrolysis-deficient mutant led to the redistribution of transferrin receptor to large crab22a-positive structures in the periphery of the cell and to a significant decrease i ...200616537905
a putative rna-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic rnai, and hypothetical mechanisms of action.all archaeal and many bacterial genomes contain clustered regularly interspaced short palindrome repeats (crispr) and variable arrays of the crispr-associated (cas) genes that have been previously implicated in a novel form of dna repair on the basis of comparative analysis of their protein product sequences. however, the proximity of crispr and cas genes strongly suggests that they have related functions which is hard to reconcile with the repair hypothesis.200616545108
essential function in vivo for dicer-2 in host defense against rna viruses in drosophila.the fruit fly drosophila melanogaster is a model system for studying innate immunity, including antiviral host defense. infection with drosophila c virus triggers a transcriptional response that is dependent in part on the jak kinase hopscotch. here we show that successful infection and killing of drosophila with the insect nodavirus flock house virus was strictly dependent on expression of the viral protein b2, a potent inhibitor of processing of double-stranded rna mediated by the essential rn ...200616554838
[use of getah virus for antiviral assay of human interferon].antiviral assay is used routinely for measuring the biological activity of interferon (ifn). however, the challenge viruses used in these assays are considered dangerous to the animal industry and pose a risk of human infection. for example, the vesicular stomatitis virus (vsv) is an important exotic disease agent in domestic animals, and the sindbis virus provokes rash, arthralgia, and fever in humans. therefore, biosafety needs to be considered when antiviral assays are performed. we chose get ...200516557019
age-dependent resistance of mice to sindbis virus infection: viral replication as a function of host age.the development of resistance of outbred white mice to two plaque size variants of sindbis virus was studied as a function of host age. a sudden drop in mortality occurred over a 3-day period. as little as 1 plaque-forming unit (pfu) per mouse was lethal in 1-day-old animals, whereas inocula of 10(9) pfu per mouse failed to produce high mortality in weanlings. a comparison of viral growth kinetics shows that early replication was similar in newborns and weanlings but that after 6 to 8 hr the pro ...197116557964
testosterone correlates with venezuelan equine encephalitis virus infection in we briefly report testosterone and cytokine responses to venezuelan equine encephalitis virus (veev) in macaques which were used as part of a larger study conducted by the department of defense to better characterize pathological responses to aerosolized veev in non-human primates. serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. infected animals exhibited a febrile response with few significant changes in cy ...200616571136
hippocampal long-term potentiation is supported by presynaptic and postsynaptic tyrosine receptor kinase b-mediated phospholipase cgamma signaling.neurotrophins have been shown to play a critical role in activity-dependent synaptic plasticity such as long-term potentiation (ltp) in the hippocampus. although the role of brain-derived neurotrophic factor (bdnf) and its tyrosine kinase receptor [tyrosine receptor kinase b (trkb)] is well documented, it still remains unresolved whether presynaptic or postsynaptic activation of trkb is involved in the induction of ltp. to address this question, we locally and specifically interfered with a down ...200616571757
recovery of a recombinant salmonid alphavirus fully attenuated and protective for rainbow trout.sleeping disease virus (sdv) is a member of the new salmonid alphavirus genus within the togaviridae family. the single-stranded rna genome of sdv is 11,894 nucleotides long, excluding the 3' poly(a) tail. a full-length cdna has been generated; the cdna was fused to a hammerhead ribozyme sequence at the 5' end and inserted into a transcription plasmid (pcdna3) backbone, yielding psdv. by transfection of psdv into fish cells, recombinant sdv (rsdv) was successfully recovered. demonstration of the ...200616571825
formation of nsp3-specific protein complexes during sindbis virus replication.alphaviruses are arthropod-borne viruses (arboviruses) that include a number of important human and animal pathogens. their replication proceeds in the cytoplasm of infected cells and does not directly depend on nuclei. alphaviruses encode only four nonstructural proteins that are required for the replication of viral genome and transcription of the subgenomic rna. however, the replicative enzyme complexes (rcs) appear to include cellular proteins and assemble on cellular organelles. we have dev ...200616571828
hiv protease cleaves poly(a)-binding protein.the pabp [poly(a)-binding protein] is able to interact with the 3' poly(a) tail of eukaryotic mrna, promoting its translation. cleavage of pabp by viral proteases encoded by several picornaviruses and caliciviruses plays a role in the abrogation of cellular protein synthesis. we report that infection of mt-2 cells with hiv-1 leads to efficient proteolysis of pabp. analysis of pabp integrity was carried out in bhk-21 (baby-hamster kidney) and cos-7 cells upon individual expression of the protease ...200616594896
combining caspase and mitochondrial dysfunction inhibitors of apoptosis to limit cell death in mammalian cell cultures.apoptosis is now recognized as a significant problem in mammalian cell culture. therefore, in this study, a single gene and multigene approach to inhibit apoptosis has been examined. stable chinese hamster ovary (cho) cell lines were generated to overexpress different single, dual, and triple combinations of three apoptosis inhibitor genes. two upstream inhibitors involved in the mitochondrial pathway, bcl-x(l) and aven, were expressed in addition to a downstream inhibitor of caspases. the caspa ...200616598795
antiviral effect of the mammalian translation initiation factor 2alpha kinase gcn2 against rna mammals, four different protein kinases, heme-regulated inhibitor, double-stranded rna-dependent protein kinase (pkr), general control non-derepressible-2 (gcn2) and pkr-like endoplasmic reticulum kinase, regulate protein synthesis in response to environmental stresses by phosphorylating the alpha-subunit of the initiation factor 2 (eif2alpha). we now report that mammalian gcn2 is specifically activated in vitro upon binding of two nonadjacent regions of the sindbis virus (sv) genomic rna to ...200616601681
dual role of the exocyst in ampa receptor targeting and insertion into the postsynaptic membrane.intracellular membrane trafficking of glutamate receptors at excitatory synapses is critical for synaptic function. however, little is known about the specialized trafficking events occurring at the postsynaptic membrane. we have found that two components of the exocyst complex, sec8 and exo70, separately control synaptic targeting and insertion of ampa-type glutamate receptors. sec8 controls the directional movement of receptors towards synapses through pdz-dependent interactions. in contrast, ...200616601687
gene therapy that safely targets and kills tumor cells throughout the body.the authors studied the therapeutic value of sindbis vectors for advanced metastatic cancer by using a variety of clinically accurate mouse models and demonstrated through imaging, histological, and molecular data that sindbis vectors systemically and specifically infect/detect and kill metastasized tumors in vivo, leading to significant suppression of tumor growth and enhanced survival. use of two different bioluminescent genetic markers for the ivis imaging system (xenogen corp., alameda, ca) ...200616608394
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