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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
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 linker.here, 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
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
vaccination with a sindbis virus-based dna vaccine expressing antigen 85b induces protective immunity against mycobacterium tuberculosis.to 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
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
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
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
[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
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
bax-like protein drob-1 protects neurons from expanded polyglutamine-induced toxicity in drosophila.bcl-2 family proteins regulate cell death through the mitochondrial apoptotic pathway. here, we show that the drosophila bax-like bcl-2 family protein drob-1 maintains mitochondrial function to protect cells from neurodegeneration. a pan-neuronal knockdown of drob-1 results in lower locomotor activity and a shorter lifespan in adult flies. either the rnai-mediated downregulation of drob-1 or overexpression of drob-1 antagonist buffy strongly enhances the polyglutamine-induced accumulation of ubi ...200516001086
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
[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
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
sindbis virus: propagation, quantification, and storage.the prototype of the alphaviruses, sindbis virus, has a broad host range. in nature, sindbis virus shuttles from an insect vector to a vertebrate host and back to the insect vector in a complex transmission cycle. sindbis virus must, therefore, be able to replicate in two biochemically and genetically divergent hosts, invertebrates and vertebrates. in the laboratory, sindbis grows to high titers in a large variety of cultured cells of both vertebrate and invertebrate origin. sindbis virus is eas ...200518770557
sindbis vectors: illuminating the path to ovarian cancer therapy. 200519202635
larval competition differentially affects arbovirus infection in aedes mosquitoes.both density-mediated and trait-mediated indirect biotic interactions may be important in structuring communities. indirect interactions in many study systems remain unexplored; in part, because they are often difficult to detect, and in many instances, have been identified empirically only when unexpected results arise. indirect effects induced by competition may be particularly important among organisms with complex life cycles, wherein competitive effects experienced in one life stage influen ...200519096729
insight into a conserved lifestyle: protein-carbohydrate adhesion strategies of vector-borne pathogens. 200516299269
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
the dynamic synapse: molecular methods in ionotropic receptor biologythe ability to molecularly manipulate protein expression in the rodent brain has proven to be a powerful tool in neuroscience. specifically, the generation of transgenic mouse lines has allowed scientists to begin to answer important questions about the functional role of specific proteins. however, this technique still suffers from the lack of strict temporal and spatial regulation of protein expression as well as the possibility of genetic compensation. more recently, the expression of heterol ...200621204479
plasma phenoloxidase of the larval tobacco budworm, heliothis virescens, is virucidal.heliothis virescens larval plasma contains high levels of an antiviral activity against the budded form of the helicoverpa zea single nucleopolyhedrovirus (hzsnpv) in vitro. preliminary results indicated that phenoloxidase is primarily responsible for this virucidal effect. however it is known that other enzymes that generate antimicrobial reactive oxygen intermediates and reactive nitrogen intermediates are present in hemolymph that could contribute to the observed virucidal activity. to elucid ...200619537988
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
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
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
characterization of a novel 5' subgenomic rna3a derived from rna3 of brome mosaic bromovirus.the synthesis of 3' subgenomic rna4 (sgrna4) by initiation from an internal sg promoter in the rna3 segment was first described for brome mosaic bromovirus (bmv), a model tripartite positive-sense rna virus (w. a. miller, t. w. dreher, and t. c. hall, nature 313:68-70, 1985). in this work, we describe a novel 5' sgrna of bmv (sgrna3a) that we propose arises by premature internal termination and that encapsidates in bmv virions. cloning and sequencing revealed that, unlike any other bmv rna segme ...200617005659
catalytic core of alphavirus nonstructural protein nsp4 possesses terminal adenylyltransferase activity.the rna-dependent rna polymerase nsp4 is an integral part of the alphavirus replication complex. to define the role of nsp4 in viral rna replication and for a structure-function analysis, we expressed sindbis virus nsp4 in escherichia coli. the core catalytic domain of nsp4 (delta97nsp4, a deletion of the n-terminal 97 amino acids), which consists of the predicted polymerase domain containing the gdd amino acid motif required for viral rna synthesis, was stable against proteolytic degradation du ...200617005674
trans regulation of cap-independent translation by a viral subgenomic rna.many positive-strand rna viruses generate 3'-coterminal subgenomic mrnas to allow translation of 5'-distal open reading frames. it is unclear how viral genomic and subgenomic mrnas compete with each other for the cellular translation machinery. translation of the uncapped barley yellow dwarf virus genomic rna (grna) and subgenomic rna1 (sgrna1) is driven by the powerful cap-independent translation element (bte) in their 3' untranslated regions (utrs). the bte forms a kissing stem-loop interactio ...200617005682
rabies virus infection of primary neuronal cultures and adult mice: failure to demonstrate evidence of excitotoxicity.cultures derived from the cerebral cortices and hippocampi of 17-day-old mouse fetuses infected with the cvs strain of rabies virus showed loss of trypan blue exclusion, morphological apoptotic features, and activated caspase 3 expression, indicating apoptosis. the nmda (n-methyl-d-aspartate acid) antagonists ketamine (125 microm) and mk-801 (60 microm) were found to have no significant neuroprotective effect on cvs-infected neurons, while the caspase inhibitor ac-asp-glu-val aspartic acid aldeh ...200617005706
pkcdelta alternatively spliced isoforms modulate cellular apoptosis in retinoic acid-induced differentiation of human nt2 cells and mouse embryonic stem cells.nt2 cells are a human teratocarcinoma cell line that, upon treatment with retinoic acid (ra), begin differentiating into a neuronal phenotype. the transformation of undifferentiated nt2 cells into hnt neurons presents an opportunity to investigate the mechanisms involved in neurogenesis because a key component is cell apoptosis, which is essential for building neural networks. protein kinase cdelta (pkcdelta) plays an important role as a mediator of cellular apoptosis in response to various stim ...200617017122
indolopyridones inhibit human immunodeficiency virus reverse transcriptase with a novel mechanism of action.we have discovered a novel class of human immunodeficiency virus (hiv) reverse transcriptase (rt) inhibitors that block the polymerization reaction in a mode distinct from those of the nucleoside or nucleotide rt inhibitors (nrtis) and nonnucleoside rt inhibitors (nnrtis). for this class of indolopyridone compounds, steady-state kinetics revealed competitive inhibition with respect to the nucleotide substrate. despite substantial structural differences with classical chain terminators or natural ...200617020946
activity- and mtor-dependent suppression of kv1.1 channel mrna translation in dendrites.mammalian target of rapamycin (mtor) is implicated in synaptic plasticity and local translation in dendrites. we found that the mtor inhibitor, rapamycin, increased the kv1.1 voltage-gated potassium channel protein in hippocampal neurons and promoted kv1.1 surface expression on dendrites without altering its axonal expression. moreover, endogenous kv1.1 mrna was detected in dendrites. using kv1.1 fused to the photoconvertible fluorescence protein kaede as a reporter for local synthesis, we obser ...200617023663
manipulating kv4.2 identifies a specific component of hippocampal pyramidal neuron a-current that depends upon kv4.2 expression.the somatodendritic a-current, i(sa), in hippocampal ca1 pyramidal neurons regulates the processing of synaptic inputs and the amplitude of back propagating action potentials into the dendritic tree, as well as the action potential firing properties at the soma. in this study, we have used rna interference and over-expression to show that expression of the kv4.2 gene specifically regulates the i(sa) component of a-current in these neurons. in dissociated hippocampal pyramidal neuron cultures, or ...200617026528
replicase-based dna vaccines for allergy treatment.replicase-based vaccines were introduced to overcome some of the deficiencies of conventional dna- and rna-based vaccines, including poor efficiency and low stability. at ultra-low doses, these alphavirus-derived vectors elicit cellular as well as humoral immune responses. additionally, replicase-based vectors induce "self-removal" of the vaccine via apoptosis of transfected cells. this chapter describes the construction of a replicon-based dna vaccine vector from commercially available plasmids ...200616988457
cyclophosphamide increases transgene expression mediated by an oncolytic adenovirus in glioma-bearing mice monitored by bioluminescence imaging.approaches to improve the oncolytic potency of replication-competent adenoviruses include the insertion of therapeutic transgenes into the viral genome. little is known about the levels and duration of in vivo transgene expression by cells infected with such "armed" viruses. using a tumor-selective adenovirus encoding firefly luciferase (addelta24cmv-luc) we investigated these questions in an intracranial mouse model for malignant glioma. luciferase expression was detected by bioluminescence ima ...200616996314
identification of japanese encephalitis virus-inducible genes in mouse brain and characterization of garg39/ifit2 as a microtubule-associated protein.several mouse central nervous system genes have been identified that are differentially regulated during japanese encephalitis virus (jev) infection, including those which have not been reported to be induced by any other neurotropic virus. interestingly, approximately 80 % of jev-inducible genes identified in this study are also induced by sindbis virus, indicating activation of common host signalling pathways by these two viruses, despite their diverse life cycles. one of these, the glucocorti ...200617030862
antilipopolysaccharide factor interferes with white spot syndrome virus replication in vitro and in vivo in the crayfish pacifastacus leniusculus.in a study of genes expressed differentially in the freshwater crayfish pacifastacus leniusculus infected experimentally with the white spot syndrome virus (wssv), one protein, known as antilipopolysaccharide factor (alf), was chosen, among those whose transcript levels increased upon viral infection, for further studies. alf rna interference (rnai) experiments in whole animals and in cell cultures indicated that alf can protect against wssv infection, since knockdown of alf by rnai specifically ...200617041217
arc/arg3.1 interacts with the endocytic machinery to regulate ampa receptor trafficking.arc/arg3.1 is an immediate-early gene whose mrna is rapidly transcribed and targeted to dendrites of neurons as they engage in information processing and storage. moreover, arc/arg3.1 is known to be required for durable forms of synaptic plasticity and learning. despite these intriguing links to plasticity, arc/arg3.1's molecular function remains enigmatic. here, we demonstrate that arc/arg3.1 protein interacts with dynamin and specific isoforms of endophilin to enhance receptor endocytosis. arc ...200617088211
increased expression of the immediate-early gene arc/arg3.1 reduces ampa receptor-mediated synaptic transmission.arc/arg3.1 is an immediate-early gene whose expression levels are increased by strong synaptic activation, including synapse-strengthening activity patterns. arc/arg3.1 mrna is transported to activated dendritic regions, conferring the distribution of arc/arg3.1 protein both temporal correlation with the inducing stimulus and spatial specificity. here, we investigate the effect of increased arc/arg3.1 levels on synaptic transmission. surprisingly, arc/arg3.1 reduces the amplitude of synaptic cur ...200617088212
arc/arg3.1 mediates homeostatic synaptic scaling of ampa receptors.homeostatic plasticity may compensate for hebbian forms of synaptic plasticity, such as long-term potentiation (ltp) and depression (ltd), by scaling neuronal output without changing the relative strength of individual synapses. this delicate balance between neuronal output and distributed synaptic weight may be necessary for maintaining efficient encoding of information across neuronal networks. here, we demonstrate that arc/arg3.1, an immediate-early gene (ieg) that is rapidly induced by neuro ...200617088213
genomic and metabolic studies of the impact of probiotics on a model gut symbiont and host.probiotics are deliberately ingested preparations of live bacterial species that confer health benefits on the host. many of these species are associated with the fermentation of dairy products. despite their increasing use, the molecular details of the impact of various probiotic preparations on resident members of the gut microbiota and the host are generally lacking. to address this issue, we colonized germ-free mice with bacteroides thetaiotaomicron, a prominent component of the adult human ...200617132046
ampar removal underlies abeta-induced synaptic depression and dendritic spine loss.beta amyloid (abeta), a peptide generated from the amyloid precursor protein (app) by neurons, is widely believed to underlie the pathophysiology of alzheimer's disease. recent studies indicate that this peptide can drive loss of surface ampa and nmda type glutamate receptors. we now show that abeta employs signaling pathways of long-term depression (ltd) to drive endocytosis of synaptic ampa receptors. synaptic removal of ampa receptors is necessary and sufficient to produce loss of dendritic s ...200617145504
the study transplacental chikungunya virus antibody kinetics, thailand.antibodies to chikungunya virus were detected by hemagglutination-inhibition assay in 33.6% of 2,000 infants' cord sera at delivery. follow-up of 24 seropositive infants showed that the half-life of antibody persistence was 35.5 days. chikungunya virus infection is common in thailand, and routine use of diagnostic assays is needed.200617283634
induction of t cell immunity by cutaneous genetic immunization with recombinant lentivector.recent studies suggest that t cell-based cellular immunity plays an important role in preventing and delaying progression of infectious and neoplastic diseases. based on these findings, recent efforts in vaccine research are giving rise to a new generation of "t cell" vaccines. the development of t cell vaccines has been problematic. current investigations are focusing on gene-based immunization strategies, including the development of non-viral "naked" plasmid dna and recombinant viral vector-b ...200617337771
antibody responses against hiv in rhesus macaques following combinations of mucosal and systemic immunizations with chimeric alphavirus-based replicon particles.mucosal and systemic transmission of hiv is prevalent. therefore, mucosal followed by parenteral immunizations with chimeric vs. complete alphavirus-based replicon particles, encoding an hiv envelope glycoprotein, were tested. female rhesus macaques were immunized intranasally and then intramuscularly. following the immunizations, enhanced mucosal and systemic antibody responses were detected with the chimeric compared to the complete replicon particles. although similar proportions of the same ...200617067269
characterization of immune responses elicited in macaques immunized sequentially with chimeric vee/sin alphavirus replicon particles expressing sivgag and/or hivenv and with recombinant hivgp140env protein.in the present study, macaques were coimmunized with veerep/sinenv chimeric alphavirus replicon particles expressing sivp55gag and hivdeltav2gp140env or only with replicon particles expressing hivdeltav2gp140env. all animals were subsequently immunized with recombinant trimeric hivdeltav2gp140env protein. during alphavirus immunization, anti-sivgag and anti-hivenv-specific interferon (ifn)-gamma responses, as well as high titers of anti-hivenv binding (gp120 but not gp41 specific) and anti-hiv n ...200617067273
immunological thresholds in neurological gene therapy: highly efficient elimination of transduced cells might be related to the specific formation of immunological synapses between t cells and virus-infected brain cells.first-generation adenovirus can be engineered with powerful promoters to drive expression of therapeutic transgenes. numerous clinical trials for glioblastoma multiforme using first generation adenoviral vectors have either been performed or are ongoing, including an ongoing, phase iii, multicenter trial in europe and israel (ark therapeutics, inc.). although in the absence of anti-adenovirus immune responses expression in the brain lasts 6-18 months, systemic infection with adenovirus induces i ...200618084640
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
cubic phases in phosphatidylcholine-cholesterol mixtures: cholesterol as membrane "fusogen".x-ray diffraction reveals that mixtures of some unsaturated phosphatidylcholines (pcs) with cholesterol (chol) readily form inverted bicontinuous cubic phases that are stable under physiological conditions. this effect was studied in most detail for dioleoyl pc/chol mixtures with molar ratios of 1:1 and 3:7. facile formation of im3m and pn3m phases with lattice constants of 30-50 nm and 25-30 nm, respectively, took place in phosphate-buffered saline, in sucrose solution, and in water near the te ...200616829556
structure determination of clathrin coats to subnanometer resolution by single particle cryo-electron microscopy.clathrin triskelions can assemble into lattices of different shapes, sizes and symmetries. for many years, the structures of clathrin lattices have been studied by single particle cryo-electron microscopy, which probed the architecture of the d6 hexagonal barrel clathrin coat at the molecular level. by introducing additional image processing steps we have recently produced a density map for the d6 barrel clathrin coat at subnanometer resolution, enabling us to generate an atomic model for this l ...200616908193
postsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber-purkinje cell synapses via bdnf.the maintenance of synaptic functions is essential for neuronal information processing, but cellular mechanisms that maintain synapses in the adult brain are not well understood. here, we report an activity-dependent maintenance mechanism of parallel fiber (pf)-purkinje cell (pc) synapses in the cerebellum. when postsynaptic metabotropic glutamate receptor (mglur) or inositol 1,4,5-trisphosphate (ip(3)) signaling was chronically inhibited in vivo, pf-pc synaptic strength decreased because of a d ...200616709674
tyrosine 311 is phosphorylated by c-abl and promotes the apoptotic effect of pkcdelta in glioma cells.in this study we characterized the phosphorylation of tyrosine 311 and its role in the apoptotic function of pkcdelta in glioma cells. we found that c-abl phosphorylated pkcdelta on tyrosine 311 in response to h2o2 and that this phosphorylation contributed to the apoptotic effect of h2o2. in contrast, src, lyn, and yes were not involved in the phosphorylation of tyrosine 311 by h2o2. a phosphomimetic pkcdelta mutant, in which tyrosine 311 was mutated to glutamic acid (pkcdeltay311e), induced a l ...200617126298
distinguishing reversible from irreversible virus capsid assembly.capsids of spherical viruses may be constructed from hundreds or thousands of copies of the major capsid protein(s). these assembly reactions are poorly understood. here we consider the predicted behavior for assembly where the component reactions have weak association energy and are reversible and compare them to essentially irreversible reactions. the comparisons are based on mass action calculations and the behavior predicted from kinetic simulations where assembly is described as a cascade o ...200617157314
functional role of aspartic proteinase cathepsin d in insect metamorphosis.metamorphosis is a complex, highly conserved and strictly regulated development process that involves the programmed cell death of obsolete larval organs. here we show a novel functional role for the aspartic proteinase cathepsin d during insect metamorphosis.200617062167
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 mice.it 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 protein.gb 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
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
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