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a single mutation in the e2 glycoprotein important for neurovirulence influences binding of sindbis virus to neuroblastoma cells.the amino acid at position 55 of the e2 glycoprotein (e2(55)) of sindbis virus (sv) is a critical determinant of sv neurovirulence in mice. recombinant virus strain te (e2(55) = histidine) differs only at this position from virus strain 633 (e2(55)= glutamine), yet te is considerably more neurovirulent than 633. te replicates better than 633 in a neuroblastoma cell line (n18), but similarly in bhk cells. immunofluorescence staining showed that most n18 cells were infected by te at a multiplicity ...200212021363
vector infection determinants of venezuelan equine encephalitis virus reside within the e2 envelope glycoprotein.epizootic subtype iab and ic venezuelan equine encephalitis viruses (veev) readily infect the epizootic mosquito vector aedes taeniorhynchus. the inability of enzootic subtype ie viruses to infect this mosquito species provides a model system for the identification of natural viral determinants of vector infectivity. to map mosquito infection determinants, reciprocal chimeric viruses generated from epizootic subtype iab and enzootic ie veev were tested for mosquito infectivity. chimeras containi ...200212021373
postsynaptic expression of a new calcium pathway in hippocampal ca3 neurons and its influence on mossy fiber long-term potentiation.long-term potentiation (ltp) in the ca1 region of the hippocampus is induced by postsynaptic ca(2+) influx via nmda receptors (nmdars). however, this synaptic plasticity occurs independently of nmdars when ca(2+)-permeable ampa receptors (ampars) are expressed at postsynaptic sites using various genetic techniques, indicating that an increase in ca(2+) level at critical postsynaptic sites, regardless of its entry pathway, triggers the induction of ltp at ca1 synapses. in contrast, nmdars are spa ...200212040036
multiple mechanisms for the potentiation of ampa receptor-mediated transmission by alpha-ca2+/calmodulin-dependent protein kinase ii.some forms of activity-dependent synaptic potentiation require the activation of postsynaptic ca(2+)/calmodulin-dependent protein kinase ii (camkii). activation of camkii has been shown to phosphorylate the glutamate receptor 1 subunit of the ampa receptor (ampar), thereby affecting some of the properties of the receptor. here, a recombinant, constitutively active form of alphacamkii tagged with the fluorescent marker green fluorescent protein (gfp) [alphacamkii(1-290)-enhanced gfp (egfp)] was e ...200212040047
contribution of t cells to mortality in neurovirulent sindbis virus encephalomyelitis.intranasal inoculation of c57bl/6 mice with a neurovirulent strain of sindbis virus (sv) results in fatal encephalomyelitis. mice with selective immune deficiencies were studied to determine the role of the immune response in fatal outcome. mortality was decreased in mice deficient in alphabeta, but not gammadelta, t cells demonstrating a contribution of alphabeta t cells. mice lacking either cd4+ or cd8+ t cells also had reduced mortality and mice lacking interferon (ifn)-gamma were completely ...200212044981
interferons mediate terminal differentiation of human cortical thymic epithelial cells.in the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional t lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise t-cell lymphopoiesis in this organ. in a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. i ...200212050353
previously infected and recovered chimpanzees exhibit rapid responses that control hepatitis c virus replication upon rechallenge.responses in three chimpanzees were compared following challenge with a clonal hepatitis c virus (hcv) contained in plasma from an animal that had received infectious rna transcripts. two of the chimpanzees (ch1552 and chx0186) had recovered from a previous infection with hcv, while the third (ch1605) was a naïve animal. all animals were challenged by reverse titration with decreasing dilutions of plasma and became serum rna positive following challenge. ch1605 displayed a typical disease profil ...200212050371
asymmetric requirement for cholesterol in receptor-bearing but not envelope-bearing membranes for fusion mediated by ecotropic murine leukemia virus.we show that fusion mediated by ecotropic murine leukemia virus envelope is dependent on cholesterol in receptor-bearing membranes. the effect is >10 times larger in insect cells than mammalian cells, probably because the former can be more extensively depleted of cholesterol. the fact that cholesterol is apparently not needed in envelope-bearing membranes suggests that it plays a role in an asymmetric step in membrane fusion and argues against a class of models in which cholesterol is important ...200212050383
protein disulfide isomerase, a component of the estrogen receptor complex, is associated with chlamydia trachomatis serovar e attached to human endometrial epithelial cells.chlamydia trachomatis serovar e, the leading bacterial agent responsible for sexually transmitted diseases, is required to invade genital epithelial cells for its growth and survival, yet little is known about the adhesin-receptor interactions promoting its entry. in contrast, much has been published on the heparan sulfate receptor for binding c. trachomatis l2 elementary bodies (ebs) prior to entry into hela cells. using a different experimental approach in which a biotinylated apical membrane ...200212065480
inhibitor specificity of recombinant and endogenous caspase-9.apoptosis triggered through the intrinsic pathway by radiation and anti-neoplastic drugs is initiated by the activation of caspase-9. to elucidate control mechanisms in this pathway we used a range of synthetic and natural reagents. the inhibitory potency of acetyl-asp-glu-val-asp-aldehyde ('ac-devd-cho'), benzyloxycarbonyl-val-ala-asp-fluoromethylketone ('z-vad-fmk') and the endogenous caspase inhibitor x-chromosome-linked inhibitor of apoptosis protein ('xiap') against recombinant caspase-9 we ...200212067274
fusion of alphaviruses with liposomes is a non-leaky process.it has been reported that low-ph-induced fusion of influenza virus with liposomes results in rapid and extensive release of both low- and high-molecular-weight substances from the liposomes [günther-ausborn et al., j. biol. chem. 270 (1995) 29279-29285; shangguan et al., biochemistry 35 (1996) 4956-4965]. here, we demonstrate retention of encapsulated water-soluble compounds during fusion of semliki forest virus (sfv) or sindbis virus with liposomes at low ph. under conditions allowing complete ...200212067727
mass spectrometry-based proteolytic mapping for rapid virus identification.a novel method is proposed for rapid identification of viruses and other organisms that show a low number of biomarkers, based on the construction of databases of organism-specific tryptic peptide masses. the peptide products of any protease that cuts at specific residues can be accommodated. experimentally, a sample of intact virus, e.g., one collected from the atmosphere, is digested with a selective protease for a short time, and the digestion products are analyzed by maldi-tof mass spectrome ...200212069233
the lipopolysaccharide and beta-1,3-glucan binding protein gene is upregulated in white spot virus-infected shrimp (penaeus stylirostris).pattern recognition proteins such as lipopolysaccharide and beta-1,3-glucan binding protein (lgbp) play an important role in the innate immune response of crustaceans and insects. random sequencing of cdna clones from a hepatopancreas cdna library of white spot virus (wsv)-infected shrimp provided a partial cdna (psest-289) that showed similarity to the lgbp gene of crayfish and insects. subsequently full-length cdna was cloned by the 5'-race (rapid amplification of cdna ends) technique and sequ ...200212072514
aura virus structure suggests that the t=4 organization is a fundamental property of viral structural proteins.aura and sindbis viruses are closely related alphaviruses. unlike other alphaviruses, aura virus efficiently encapsidates both genomic rna (11.8 kb) and subgenomic rna (4.2 kb) to form virus particles. previous studies on negatively stained aura virus particles predicted that there were two major size classes with potential t=3 and t=4 capsid structures. we have used cryoelectron microscopy and three-dimensional image reconstruction techniques to examine the native morphology of different classe ...200212072523
positional cloning of the murine flavivirus resistance gene.inbred mouse strains exhibit significant differences in their susceptibility to viruses in the genus flavivirus, which includes human pathogens such as yellow fever, dengue, and west nile virus. a single gene, designated flv, confers this differential susceptibility and was mapped previously to a region of mouse chromosome 5. a positional cloning strategy was used to identify 22 genes from the flv gene interval including 10 members of the 2'-5'-oligoadenylate synthetase gene family. one 2'-5'-ol ...200212080145
involvement of fes/fps tyrosine kinase in semaphorin3a signaling.collapsin response mediator proteins (crmps)/toad64/ulips/drps and cram have emerged as strong candidates for a role in semaphorin signaling. in this study we identified fes/fps (fes) tyrosine kinase in the crmp-cram complex and investigated whether fes was involved in semaphorin3a (sema3a) signaling. in cos-7 cells, the interaction between fes and plexina1 (plexa1) and the tyrosine phosphorylation of plexa1 by fes were observed; however, these events were significantly attenuated by co-expressi ...200212093729
prolonged arthritis associated with sindbis-related (pogosta) virus infection. 200212096239
matrix metalloproteinase expression correlates with virulence following neurotropic mouse hepatitis virus infection.the relationship(s) between viral virulence and matrix metalloproteinase (mmp) expression in the central nervous system (cns) of mice undergoing lethal and sublethal infections with neurotropic mouse hepatitis virus was investigated. lethal infection induced increased levels of mmp-3 and mmp-12 mrnas as well as that of tissue inhibitor of matrix metalloproteinases 1 (timp-1) compared to sublethal infection. increased induction of mmp, timp, and chemokine expression correlated with increased viru ...200212097550
generation of amyloid beta peptide with pyroglutamate at position 3 in primary cortical neurons.the majority of amyloid beta peptide (abeta) deposited in the brains of alzheimer's disease (ad) patients is n-truncated, especially abeta starting with pyroglutamate at position 3 (abeta(3(pe))). to develop a system in which abeta(3(pe)) is generated in primary neurons and to clarify the cyclization mechanism of n-terminal glutamate, we constructed amyloid precursor protein complementary dnas which encoded a potential precursor for abeta(3(pe)) by amino acid substitution and deletion. among the ...200212098492
dissection of c-mos degron.c-mos, a map kinase kinase kinase, is a regulator of oocyte maturation. the concentration of c-mos is controlled in part through its conditional degradation. previous studies proposed the "second-codon rule", according to which the n-terminal proline (pro) of c-mos is a destabilizing residue that targets c-mos for degradation. we analyzed the degradation signal (degron) of c-mos in xenopus oocytes, found it to be a portable degron, and demonstrated that, contrary to the model above, the n-termin ...200212426378
alphaviral vectors for gene transfer into neurons.alphaviruses are small, enveloped positive-strand rna viruses that have been successfully transformed into expression vectors in the case of semliki forest virus (sfv), sindbis virus (sin), and venezuelan equine encephalitis virus. compared to other viral vectors, their advantages are easy and fast generation of recombinant viral particles, rapid onset, and high-level transgene expression. when applied to neuronal tissue, sfv and sin vectors possess the additional advantage of efficiently and pr ...200212428755
broad-spectrum virus reduction in red cell concentrates using inactine pen110 chemistry.the risk of transmission of blood-borne pathogens by transfusion is a persistent problem in medicine. to address this safety issue, inactine pen110 chemistry is being utilized to develop a process for preparing pathogen-reduced red blood cell concentrates (rbcc). the purpose of this study was to characterize the virucidal effectiveness of the inactine pen110 chemistry in full units of rbcc by using a panel of viruses with diverse properties in composition, size and shape.200212437518
effects of membrane potential and sphingolipid structures on fusion of semliki forest virus.cells expressing the e1 and e2 envelope proteins of semliki forest virus (sfv) were fused to voltage-clamped planar lipid bilayer membranes at low ph. formation and evolution of fusion pores were electrically monitored by capacitance measurements, and membrane continuity was tracked by video fluorescence microscopy by including rhodamine-phosphatidylethanolamine in the bilayer. fusion occurred without leakage for a negative potential applied to the trans side of the planar membrane. when a posit ...200212438595
novel mutations that control the sphingolipid and cholesterol dependence of the semliki forest virus fusion protein.the enveloped alphavirus semliki forest virus (sfv) infects cells via a membrane fusion reaction mediated by the e1 membrane protein. efficient sfv-membrane fusion requires the presence of cholesterol and sphingolipid in the target membrane. here we report on two mutants, srf-4 and srf-5, selected for growth in cholesterol-depleted cells. like the previously isolated srf-3 mutant (e1 proline 226 to serine), the phenotypes of the srf-4 and srf-5 mutants were conferred by single-amino-acid changes ...200212438597
endocytosis is a critical step in entry of subgroup b avian leukosis viruses.the avian leukosis virus (alv) entry mechanism is controversial, with evidence for and against a low-ph requirement for viral fusion. to further address this question, we tested the entry of human immunodeficiency virus type 1 (hiv-1) pseudotyped with the envelope protein of subgroup b alv (alv-b) in the presence of three different lysosomotropic agents. these lysosomotropic agents were able to block the entry of wild-type and pseudotyped alv-b in two different cell lines, strongly suggesting th ...200212438612
polysulfonates derived from metal thiolate complexes as inhibitors of hiv-1 and various other enveloped viruses in vitro.sodium 2-mercaptoethanesulfonate reacts with the metal ions pd(ii), pt(ii), ag(i), cd(ii) and zn(ii) to yield complexes containing multiple anionic sulfonate sites. on the basis of spectroscopic and other analytical data the complexes were assigned the tentative molecular formulas: pd6(sch2ch2so3na)12, ptn(sch2ch2so3na)2n+2, agn(sch2ch2so3na)n, na2zn4(sch2ch2so3na)10, and na2cd4(sch2ch2so3na)10. the complexes displayed a variety of differences in activity towards dna and rna viruses. the platinu ...200212448691
in vivo antitumor activity of sindbis viral vectors.sindbis virus, a blood-borne virus transmitted by mosquitoes, has been used as a vector to efficiently express exogenous genes in vitro and in vivo and to induce apoptosis. because sindbis virus infects mammalian cells by interacting with the high-affinity laminin receptors, which are expressed at higher levels in several human cancers than in normal cells, we determined whether a sindbis viral vector could be used to target cancers in vivo.200212464651
alphavirus vectors as tools in cancer gene therapy.alphavirus vectors, particularly those based on the replicon of semliki forest virus, have shown great potential as gene delivery vehicles for various applications in cancer gene therapy. the rapid production of high-titer recombinant sfv particles, which show impressive transduction rates in various mammalian cell lines, primary cultures and in vivo, results in high levels of transgene expression. additionally, sfv vectors induce apoptosis in transduced host cells, which can further increase th ...200212614181
abstracts of the fourth international symposium on molecular insect science. may 28-june 2, 2002. tucson, arizona, usa. 200215455051
semliki forest virus and sindbis virus vectors.semliki forest virus (sfv) and sindbis virus (sin) are two, positive-strand rna viruses of the alphavirus genus. vectors for both have been developed to express high levels of foreign genes in vitro and in vivo. basic protocol 1 describes the preparation of packaged sfv and sin replicons by co-electroporation of helper and vector rna into baby hamster kidney (bhk)-21 cells. basic protocol 2 describes the activation of packaged sfv replicons with a-chymotrypsin. basic protocol 3 provides a method ...200218428324
unique inflammatory rna profiles of microglia in creutzfeldt-jakob disease.previous studies in creutzfeldt-jakob disease (cjd) have shown that myeloid cells in the periphery as well as derivative microglial cells in the brain are infectious. microglia can show an activated phenotype before prion protein (prp) pathology is detectable in brain, and isolated infectious microglia contain very little prp. to find whether a set of inflammatory genes are significantly induced or suppressed with infection, we analyzed rna from isolated microglia with relevant cdna arrays, and ...200312525699
p250gap, a novel brain-enriched gtpase-activating protein for rho family gtpases, is involved in the n-methyl-d-aspartate receptor signaling.n-methyl-d-aspartate (nmda) receptors regulate structural plasticity by modulating actin organization within dendritic spines. herein, we report identification and characterization of p250gap, a novel gtpase-activating protein for rho family proteins that interacts with the glurepsilon2 (nr2b) subunit of nmda receptors in vivo. the p250gap mrna was enriched in brain, with high expression in cortex, corpus striatum, hippocampus, and thalamus. within neurons, p250gap was highly concentrated in the ...200312857875
experience strengthening transmission by driving ampa receptors into synapses.the mechanisms underlying experience-dependent plasticity in the brain may depend on the ampa subclass of glutamate receptors (ampa-rs). we examined the trafficking of ampa-rs into synapses in the developing rat barrel cortex. in vivo gene delivery was combined with in vitro recordings to show that experience drives recombinant glur1, an ampa-r subunit, into synapses formed between layer 4 and layer 2/3 neurons. moreover, expression of the glur1 cytoplasmic tail, a construct that inhibits synapt ...200312624270
facilitation of dendritic mrna transport by cpeb.in neurons, the proteins derived from mrnas localized in dendrites have been implicated in synaptic plasticity. the cytoplasmic polyadenylation element (cpe), a cis element in the 3'-utrs of specific dendritic mrnas, promotes cytoplasmic polyadenylation-induced translation in response to synaptic stimulation. here, we demonstrate that the cpe and its binding protein cpeb facilitate mrna transport to dendrites. in rat hippocampal neurons infected with recombinant viruses, the cpe is sufficient to ...200312629046
american genotype structures decrease dengue virus output from human monocytes and dendritic cells.the dengue virus type 2 structures probably involved in human virulence were previously defined by sequencing the complete genome of both american and southeast (se) asian genotype templates in patient serum (k. c. leitmeyer et al., j. virol. 73:4738-4747, 1999). we have now evaluated the effects of introducing a mutation in the envelope glycoprotein (e) gene and/or replacement of 5'- and 3'-nontranslated regions on dengue virus replication in human primary cell cultures. a series of chimeric in ...200312634353
hepatitis c virus glycoproteins interact with dc-sign and dc-signr.dc-sign and dc-signr are two closely related membrane-associated c-type lectins that bind human immunodeficiency virus (hiv) envelope glycoprotein with high affinity. binding of hiv to cells expressing dc-sign or dc-signr can enhance the efficiency of infection of cells coexpressing the specific hiv receptors. dc-sign is expressed on some dendritic cells, while dc-signr is localized to certain endothelial cell populations, including hepatic sinusoidal endothelial cells. we found that soluble ver ...200312634366
the abundant nuclear enzyme parp participates in the life cycle of simian virus 40 and is stimulated by minor capsid protein vp3.the abundant nuclear enzyme poly(adp-ribose) polymerase (parp) functions in dna damage surveillance and repair and at the decision between apoptosis and necrosis. here we show that parp binds to simian virus 40 (sv40) capsid proteins vp1 and vp3. furthermore, its enzymatic activity is stimulated by vp3 but not by vp1. experiments with purified mutant proteins demonstrated that the parp binding domain in vp3 is localized to the 35 carboxy-terminal amino acids, while a larger peptide of 49 amino a ...200312634384
engineering the transmissible gastroenteritis virus genome as an expression vector inducing lactogenic immunity.the genome of the coronavirus transmissible gastroenteritis virus (tgev) has been engineered as an expression vector with an infectious cdna. the vector led to the efficient (>40 micro g/10(6) cells) and stable (>20 passages) expression of a heterologous gene (green fluorescent protein [gfp]), driven by the transcription-regulating sequences (trs) of open reading frame (orf) 3a inserted in the site previously occupied by the nonessential orfs 3a and 3b. expression levels driven by this trs were ...200312634392
diverse dengue type 2 virus populations contain recombinant and both parental viruses in a single mosquito host.envelope (e) protein genes sampled from populations of dengue 2 (den-2) virus in individual aedes aegypti mosquitoes and in serum from dengue patients were copied to cdna, cloned, and sequenced. the nucleotide sequences of the e genes in more than 70% of the clones differed from the consensus sequence for the corresponding virus population at up to 11 sites, and 24 of the 94 clones contained at least one stop codon. virus populations recovered up to 2 years apart yielded clones with similar poly ...200312634407
development of an orally infectious sindbis virus transducing system that efficiently disseminates and expresses green fluorescent protein in aedes aegypti.we have constructed an orally infectious sindbis virus, me2/5'2j/gfp, that expresses green fluorescent protein (gfp) in the midgut of aedes aegypti and in other tissues as the virus disseminates. this virus has two unique features that are improvements over the sin-based expression systems currently used in mosquitoes. first, a subgenomic rna promoter and gfp coding sequence is located 5'- to the second subgenomic promoter and structural genes of the virus. second, the e2 glycoprotein gene of te ...200312653932
foamy virus envelope glycoprotein-mediated entry involves a ph-dependent fusion process.in general, enveloped viruses use two different entry strategies and are classified accordingly into ph-dependent and ph-independent viruses. different members of the retrovirus family use one or the other strategy. little is known about the uptake of foamy viruses (fv), a special group of retroviruses, into the target cells. in this study, we examined the ph dependence of fv entry by analyzing fv envelope glycoprotein (env)-mediated infection of target cells with murine leukemia virus or fv vec ...200312663779
kinetics of cd4+ and cd8+ memory t-cell responses during hepatitis c virus rechallenge of previously recovered chimpanzees.the immunological correlates of hepatitis c virus (hcv)-specific immunity are not well understood. antibodies to hcv structural proteins do not appear to play a key role in clearance of the virus and do not persist after recovery. here, we studied the kinetics of the cellular immune responses of three hcv-recovered chimpanzees during rechallenge with increasing doses of homologous hcv. although hcv envelope antibodies remained undetectable throughout the rechallenge, all animals mounted rapid hc ...200312663785
complexes of poliovirus serotypes with their common cellular receptor, cd155.structures of all three poliovirus (pv) serotypes (pv1, pv2, and pv3) complexed with their cellular receptor, pv receptor (pvr or cd155), were determined by cryoelectron microscopy. both glycosylated and fully deglycosylated cd155 exhibited similar binding sites and orientations in the viral canyon for all three pv serotypes, showing that all three serotypes use a common mechanism for cell entry. difference maps between the glycosylated and deglycosylated cd155 complexes determined the sites of ...200312663789
morphological variants of sindbis virus produced by a mutation in the capsid protein.sindbis virus is a complex aggregate of rna, protein and lipid. the virus is organized as two nested t = 4 icosahedral protein shells between which is sandwiched a lipid bilayer. the virus rna resides within the inner protein shell. the inner protein shell is attached to the outer protein shell through contacts to proteins in the outer shell, which penetrate the lipid bilayer. the data presented in the following manuscript show that mutations in the capsid protein can result in the assembly of t ...200312667814
bak alters neuronal excitability and can switch from anti- to pro-death function during postnatal development.bak is a pro-apoptotic bcl-2 family protein that localizes to mitochondria. here we evaluate the function of bak in several mouse models of neuronal injury including neuronotropic sindbis virus infection, parkinson's disease, ischemia/stroke, and seizure. bak promotes or inhibits neuronal death depending on the specific death stimulus, neuron subtype, and stage of postnatal development. bak protects neurons from excitotoxicity and virus infection in the hippocampus. as mice mature, bak is conver ...200312689595
attenuated salmonella enterica serovar typhi and shigella flexneri 2a strains mucosally deliver dna vaccines encoding measles virus hemagglutinin, inducing specific immune responses and protection in cotton rats.measles remains a leading cause of child mortality in developing countries. residual maternal measles antibodies and immunologic immaturity dampen immunogenicity of the current vaccine in young infants. because cotton rat respiratory tract is susceptible to measles virus (mv) replication after intranasal (i.n.) challenge, this model can be used to assess the efficacy of mv vaccines. pursuing a new measles vaccine strategy that might be effective in young infants, we used attenuated salmonella en ...200312692223
luciferase imaging of a neurotropic viral infection in intact animals.the identification of viral determinants of virulence and host determinants of susceptibility to virus-induced disease is essential for understanding the pathogenesis of infection. obtaining this information requires infecting large numbers of animals to assay amounts of virus in a variety of organs and to observe the onset and progression of disease. as an alternative approach, we have used a murine model of viral encephalitis and an in vivo imaging system that can detect light generated by luc ...200312692235
human rhinovirus type 2 is internalized by clathrin-mediated endocytosis.using several approaches, we investigated the importance of clathrin-mediated endocytosis in the uptake of human rhinovirus serotype 2 (hrv2). by means of confocal immunofluorescence microscopy, we show that k(+) depletion strongly reduces hrv2 internalization. viral uptake was also substantially reduced by extraction of cholesterol from the plasma membrane with methyl-beta-cyclodextrin, which can inhibit clathrin-mediated endocytosis. in accordance with these data, overexpression of dynamin k44 ...200312692238
immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid r+win55,212.theiler murine encephalomyelitis virus-induced demyelinating disease (tmev-idd) is a mouse model of chronic-progressive multiple sclerosis (ms) characterized by th1-mediated cns demyelination and spastic hindlimb paralysis. existing ms therapies reduce relapse rates in 30% of relapsing-remitting ms patients, but are ineffective in chronic-progressive disease, and their effects on disability progression are unclear. experimental studies demonstrate cannabinoids are useful for symptomatic treatmen ...200312697742
modified apoptotic molecule (bid) reduces hepatitis c virus infection in mice with chimeric human livers.hepatitis c virus (hcv) encodes a polyprotein consisting of core, envelope (e1, e2, p7), and nonstructural polypeptides (ns2, ns3, ns4a, ns4b, ns5a, ns5b). the serine protease (ns3/ns4a), helicase (ns3), and polymerase (ns5b) constitute valid targets for antiviral therapy. we engineered bh3 interacting domain death agonist (bid), an apoptosis-inducing molecule, to contain a specific cleavage site recognized by the ns3/ns4a protease. cleavage of the bid precursor molecule by the viral protease ac ...200312704395
genetic screen for monitoring hepatitis c virus ns3 serine protease activity.we have developed a genetic system to monitor the activity of the hepatitis c virus (hcv) ns3 serine protease. this genetic system is based on the bacteriophage lambda regulatory circuit where the viral repressor ci is specifically cleaved to initiate the switch from lysogeny to lytic infection. an hcv protease-specific target, ns5a-5b, was inserted into the lambda phage ci repressor. the target specificity of the hcv ns5a-5b repressor was evaluated by coexpression of this repressor with a beta- ...200312709356
the prevalence of antibodies against sindbis-related (pogosta) virus in different parts of finland.to study the occurrence of sindbis-related (pogosta) disease in finland by serological means.200312709538
effects of collagen matrix on sindbis virus infection of bhk cells.the effects of extracellular matrix (ecm) components on the outcomes of alphavirus interaction with cells are not known. studies that address such interactions have to address several methodological difficulties, including: the survival of the cells within the matrix; the passage of the virus through the matrix to infect embedded cells; and the dissociation of cells and matrix into single-cell suspension, before and after virus infection, for quantitative analysis. herein, these issues were addr ...200312711058
sindbis virus vectors designed to express a foreign protein as a cleavable component of the viral structural polyprotein.alphavirus-based expression vectors commonly use a duplicated 26s promoter to drive expression of a foreign gene. here we describe an expression strategy in which the foreign sequences are linked to the gene encoding the 2a protease of foot-and-mouth disease virus and then inserted in frame between the capsid and e3 genes of sindbis virus. during replication, the 2a fusion protein is synthesized as a component of the viral structural polyprotein that is then released by intramolecular cleavages ...200312719552
effect of p38 mitogen-activated protein kinase on the replication of encephalomyocarditis virus.cellular phosphorylation events during viral infection are necessary for effective viral replication. encephalomyocarditis (emc) virus has been used for studies on the molecular mechanisms of viral replication, but little is known about the cellular signaling pathways involved. this investigation was initiated to determine whether mitogen-activated protein kinases (mapks), which are central components of signal transduction pathways in the regulation of cell proliferation, play a role in the rep ...200312719557
vesicular stomatitis viruses with rearranged genomes have altered invasiveness and neuropathogenesis in mice.transcription of vesicular stomatitis virus is controlled by the position of a gene relative to the single 3' genomic promoter: promoter-proximal genes are transcribed at higher levels than those in more 5' distal positions. in previous work, we generated viruses having rearranged gene orders. these viruses had the promoter-proximal gene that encodes the nucleocapsid protein, n, moved to the second or fourth position in the genome in combination with the glycoprotein gene, g, moved from its usua ...200312719567
human immunodeficiency virus type 1 envelope-mediated neuropathogenesis: targeted gene delivery by a sindbis virus expression vector.sindbis virus (sin) expression vectors offer the opportunity for studying neuropathogenesis because of their distinct neural cell tropism. here, we demonstrate that a recombinant sin vector expressing egfp (sinrep5-egfp) infected multiple cell types including neural cells from several species relevant to lentivirus pathogenesis with high levels of transgene expression. infection of human neurons by a recombinant sin (sinrep5-jrfl) expressing the full-length envelope from a neurovirulent human im ...200312726727
activation of fusion by the ser virus f protein: a low-ph-dependent paramyxovirus entry process.ser virus, a paramyxovirus closely related to simian virus 5, induces no syncytium formation. the ser virus f protein has a long cytoplasmic tail (ct), and truncation or mutations of the ct result in enhanced syncytium formation (s. seth, a. vincent, and r. w. compans, j. virol. 77:167-178, 2003; s. tong, m. li, a. vincent, r. w. compans, e. fritsch, r. beier, c. klenk, m. ohuchi, and h.-d. klenk, virology 301:322-333, 2002). we hypothesized that the presence of the long ct serves to stabilize t ...200312743308
prevalence of sindbis-related (pogosta) virus infections in patients with arthritis.to determine the role of pogosta virus as a triggering infection in non-specific arthritis.200312747277
identification of a heparin-binding motif on adeno-associated virus type 2 capsids.infection of cells with adeno-associated virus (aav) type 2 (aav-2) is mediated by binding to heparan sulfate proteoglycan and can be competed by heparin. mutational analysis of aav-2 capsid proteins showed that a group of basic amino acids (arginines 484, 487, 585, and 588 and lysine 532) contribute to heparin and hela cell binding. these amino acids are positioned in three clusters at the threefold spike region of the aav-2 capsid. according to the recently resolved atomic structure for aav-2, ...200314512555
bioluminescence imaging reveals systemic dissemination of herpes simplex virus type 1 in the absence of interferon receptors.herpes simplex virus type 1 (hsv-1) can produce disseminated, systemic infection in neonates and patients with aids or other immunocompromising diseases, resulting in significant morbidity and mortality in spite of antiviral therapy. components of host immunity that normally limit hsv-1 to localized epithelial and neuronal infection remain incompletely defined. we used in vivo bioluminescence imaging to determine effects of type i and ii interferons (ifns) on replication and tropism of hsv-1 inf ...200314512556
the 5' untranslated region of alfalfa mosaic virus rna 1 is involved in negative-strand rna synthesis.the three genomic rnas of alfalfa mosaic virus each contain a unique 5' untranslated region (5' utr). replacement of the 5' utr of rna 1 by that of rna 2 or 3 yielded infectious replicons. the sequence of a putative 5' stem-loop structure in rna 1 was found to be required for negative-strand rna synthesis. a similar putative 5' stem-loop structure is present in rna 2 but not in rna 3.200314512577
inhibition of translation and induction of apoptosis by bunyaviral nonstructural proteins bearing sequence similarity to reaper.members of the california serogroup of bunyaviruses (family bunyaviridae) are the leading cause of pediatric viral encephalitis in north america. significant cell death is observed as part of the infection pathology. we now report that a bunyaviral nonstructural protein termed nss shows sequence similarity to reaper, a proapoptotic protein from drosophila. although nss proteins lack the reaper n-terminal motif critical for iap inhibition, they do retain other functions of reaper that map to cons ...200314517326
visualization of membrane protein domains by cryo-electron microscopy of dengue virus.improved technology for reconstructing cryo-electron microscopy (cryo-em) images has now made it possible to determine secondary structural features of membrane proteins in enveloped viruses. the structure of mature dengue virus particles was determined to a resolution of 9.5 a by cryo-em and image reconstruction techniques, establishing the secondary structural disposition of the 180 envelope (e) and 180 membrane (m) proteins in the lipid envelope. the alpha-helical 'stem' regions of the e mole ...200314528291
boosting with recombinant vaccinia increases hpv-16 e7-specific t cell precursor frequencies and antitumor effects of hpv-16 e7-expressing sindbis virus replicon particles.immunotherapy using the heterologous prime-boost regimen has emerged as an attractive approach for generating antigen-specific t-cell-mediated immune responses against tumors and infectious diseases. we have previously linked the mycobacterium tuberculosis heat-shock protein 70 (hsp70) to the hpv-16 e7 antigen creating a chimera, e7/hsp70. we found that nucleic acid vaccines encoding e7/hsp70 can generate strong antitumor immunity. recently, replication-defective sindbis virus replicon particle ...200314529828
antizyme frameshifting as a functional probe of eukaryotic translational termination.translation termination in eukaryotes is mediated by the release factors erf1 and erf3, but mechanisms of the interplay between these factors are not fully understood, due partly to the difficulty of measuring termination on eukaryotic mrnas. here, we describe an in vitro system for the assay of termination using competition with programmed frameshifting at the recoding signal of mammalian antizyme. the efficiency of antizyme frameshifting in rabbit reticulocyte lysates was reduced by addition o ...200314530443
bcl-xl/bcl-2 coordinately regulates apoptosis, cell cycle arrest and cell cycle entry.bcl-x(l) and bcl-2 inhibit both apoptosis and proliferation. in investigating the relationship between these two functions of bcl-x(l) and bcl-2, an analysis of 24 bcl-x(l) and bcl-2 mutant alleles, including substitutions at residue y28 previously reported to selectively abolish the cell cycle activity, showed that cell cycle delay and anti-apoptosis co-segregated in all cases. in determining whether bcl-2 and bcl-x(l) act in g(0) or g(1), forward scatter and pyronin y fluorescence measurements ...200314532118
expression of the zinc-finger antiviral protein inhibits alphavirus replication.the rat zinc-finger antiviral protein (zap) was recently identified as a host protein conferring resistance to retroviral infection. we analyzed zap's ability to inhibit viruses from other families and found that zap potently inhibits the replication of multiple members of the alphavirus genus within the togaviridae, including sindbis virus, semliki forest virus, ross river virus, and venezuelan equine encephalitis virus. however, expression of zap did not induce a broad-spectrum antiviral state ...200314557641
changes in mumps virus gene sequence associated with variability in neurovirulent phenotype.mumps virus is highly neurotropic and, prior to widespread vaccination programs, was the major cause of viral meningitis in the united states. nonetheless, the genetic basis of mumps virus neurotropism and neurovirulence was until recently not understood, largely due to the lack of an animal model. here, nonneurovirulent (jeryl lynn vaccine) and highly neurovirulent (88-1961 wild type) mumps virus strains were passaged in human neural cells or in chicken fibroblast cells with the goal of neuroad ...200314557647
induction of caspase-dependent apoptosis in cultured rat oligodendrocytes by murine coronavirus is mediated during cell entry and does not require virus replication.murine coronavirus mouse hepatitis virus (mhv) causes demyelination of the central nervous system (cns) in rats and mice. apoptotic oligodendrocytes have been detected in the vicinity of the cns demyelinating lesions in these animals. however, whether mhv can directly induce oligodendrocyte apoptosis has not been documented. here, we established a rat oligodendrocyte culture that is morphologically and phenotypically indistinguishable from the primary rat oligodendrocytes. using this culture, we ...200314581532
dc-sign and l-sign can act as attachment receptors for alphaviruses and distinguish between mosquito cell- and mammalian cell-derived viruses.c-type lectins such as dc-sign and l-sign, which bind mannose-enriched carbohydrate modifications of host and pathogen proteins, have been shown to bind glycoproteins of several viruses and facilitate either cis or trans infection. dc-sign and l-sign are expressed in several early targets of arbovirus infection, including dendritic cells (dcs) and cells of the reticuloendothelial system. in the present study, we show that dc-sign and l-sign can function as attachment receptors for sindbis (sb) v ...200314581539
borna disease virus glycoprotein is required for viral dissemination in neurons.borna disease virus (bdv) is a nonsegmented negative-strand rna virus with a tropism for neurons. infection with bdv causes neurological diseases in a wide variety of animal species. although it is known that the virus spreads from neuron to neuron, assembled viral particles have never been visualized in the brains of infected animals. this has led to the hypothesis that bdv spreads as nonenveloped ribonucleoproteins (rnp) rather than as enveloped viral particles. we assessed whether the viral e ...200314581559
are weak protein-protein interactions the general rule in capsid assembly? 200314585329
female lethality and apoptosis of spermatocytes in mice lacking the ubr2 ubiquitin ligase of the n-end rule pathway.substrates of the ubiquitin-dependent n-end rule pathway include proteins with destabilizing n-terminal residues. ubr1(-/-) mice, which lacked the pathway's ubiquitin ligase e3alpha, were viable and retained the n-end rule pathway. the present work describes the identification and analysis of mouse ubr2, a homolog of ubr1. we demonstrate that the substrate-binding properties of ubr2 are highly similar to those of ubr1, identifying ubr2 as the second e3 of the mammalian n-end rule pathway. ubr2(- ...200314585983
rna interference-mediated knockdown of a gata factor reveals a link to anautogeny in the mosquito aedes aegypti.blood feeding tightly regulates the reproductive cycle in anautogenous mosquitoes. vitellogenesis (the synthesis of yolk protein precursors) is a key event in the mosquito reproductive cycle and is activated in response to a blood meal. before blood feeding, aedes aegypti is in a state of reproductive arrest during which the yolk protein precursor genes (ypps) are repressed. the regulatory region of the major ypp gene vitellogenin (vg) has multiple gata-binding sites required for the high expres ...200314595016
sindbis virus-associated pathology in aedes albopictus (diptera: culicidae).virus dissemination and associated pathology were examined in aedes albopictus after intrathoracic inoculation of sindbis virus (sin), the prototypic alphavirus. at 10 days postinfection, virus rna was detected in all three-body segments of the insect. colocalization of virus antigen with structural pathology was observed in mosquito salivary glands and midgut-associated visceral muscles, representing yet another example of arbovirus-associated pathology in a mosquito host. sin antigen and gross ...200314596286
brain-derived neurotrophic factor signal enhances and maintains the expression of ampa receptor-associated pdz proteins in developing cortical neurons.postsynaptic molecules with pdz domains (pdz proteins) interact with various glutamate receptors and regulate their subcellular trafficking and stability. in rat neocortical development, the protein expression of ampa-type glutamate receptor glur1 lagged behind its mrna expression and rather paralleled an increase in pdz protein levels. one of the neurotrophins, brain-derived neurotrophic factor (bdnf), appeared to contribute to this process, regulating the pdz protein expression. in neocortical ...200314597197
virus concentration using polyethyleneimine-conjugated magnetic beads for improving the sensitivity of nucleic acid amplification tests.to enhance the sensitivity of virus detection by polymerase chain reaction (pcr) and reverse-transcriptional (rt)-pcr, we developed a novel virus concentration method using polyethyleneimine (pei)-conjugated magnetic beads. pei-magnetic beads adsorbed efficiently the enveloped viruses sindbis virus and herpes simplex 1 virus, and the nonenveloped virus sv-40, but not the nonenveloped viruses porcine parvovirus (ppv) or poliovirus, based on the pcr detection data. furthermore, the infectivity in ...200314599674
deletions in the transmembrane domain of a sindbis virus glycoprotein alter virus infectivity, stability, and host range.the alphaviruses are composed of two icosahedral protein shells, one nested within the other. a membrane bilayer derived from the host cell is sandwiched between the protein shells. the protein shells are attached to one another by protein domains which extend one of the proteins of the outer shell through the membrane bilayer to attach to the inner shell. we have examined the interaction of the membrane-spanning domain of one of the membrane glycoproteins with the membrane bilayer and with othe ...200314610193
liposomes as target membranes in the study of virus receptor interaction and membrane fusion. 200314610825
mitogenic effect of orphan receptor tr3 and its regulation by mekk1 in lung cancer cells.tr3, also known as ngfi-b or nur77, is an immediate-early response gene and an orphan member of the steroid/thyroid/retinoid receptor superfamily. we previously reported that tr3 expression was induced by apoptotic stimuli and was required for their apoptotic effect in lung cancer cells. here, we present evidence that tr3 was also induced by epidermal growth factor (egf) and serum and was required for their mitogenic effect in lung cancer cells. ectopic expression of tr3 in both h460 and calu-6 ...200314612408
translational recoding signals between gag and pol in diverse ltr retrotransposons.because of their compact genomes, retroelements (including retrotransposons and retroviruses) employ a variety of translational recoding mechanisms to express gag and pol. to assess the diversity of recoding strategies, we surveyed gag/pol gene organization among retroelements from diverse host species, including elements exhaustively recovered from the genome sequences of caenorhabditis elegans, drosophila melanogaster, schizosaccharomyces pombe, candida albicans, and arabidopsis thaliana. in c ...200314623998
detection of antibodies to alphaviruses and discrimination between antibodies to eastern and western equine encephalitis viruses in rabbit sera using a recombinant antigen and virus-specific monoclonal antibodies.three arthropod-borne alphaviruses, western equine encephalitis viruses (weev), eastern equine encephalitis viruses (eeev) and venezuelan equine encephalitis viruses are the aetiological agents of a sometimes severe encephalomyelitis in equines and humans in the new world. with regard to the different ecology and epidemiology of these viruses, a method applied in serological screening should be able to distinguish between them as well as other related members of the genus alphavirus in the ameri ...200314628996
promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene.malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. however, as yet, there is no genetic evidence for a role of autophagy genes in tumor suppression. the beclin 1 autophagy gene is monoallelically deleted in 40-75% of cases of human sporadic breast, ovarian, and prostate cancer. therefore, we used a targeted mutant mouse model to test the hypothesis that monoallelic deletion of beclin 1 promotes tum ...200314638851
a comparison of the properties of a bcl-xl variant to the wild-type anti-apoptosis inhibitor in mammalian cell cultures.the overexpression of bcl-2 and its homologues is a widely used strategy to inhibit apoptosis in mammalian cell culture systems. in this study, we have evaluated the bcl-2 homologue, bcl-x(l) and compared its effectiveness to a bcl-x(l) mutant lacking most of the non-conserved unstructured loop domain, bcl-x(l)delta (deletion of amino acids 26 through 83). the cell line, chinese hamster ovary (cho), was genetically modified to express constitutively bcl-x(l) or the bcl-x(l) variant and subjected ...200314642351
vesicular stomatitis virus expressing a chimeric sindbis glycoprotein containing an fc antibody binding domain targets to her2/neu overexpressing breast cancer cells.vesicular stomatitis virus (vsv) is a candidate for development for cancer therapy. it is an oncolytic virus that is safe in humans. recombinant virus can be made directly from plasmid components. we attempted to create a virus that targeted specifically to breast cancer cells. nonreplicating and replicating pseudotype vsv were created whose only surface glycoprotein (gp) was a sindbis gp, called sindbis-zz, modified to severely reduce its native binding function and to contain the fc-binding do ...200314644615
molecular dynamics simulations of the e1/e2 transmembrane domain of the semliki forest virus.transmembrane (tm) helix-helix interactions are important for virus budding and fusion. we have developed a simulation strategy that reveals the main features of the helical packing between the tm domains of the two glycoproteins e1 and e2 of the alpha-virus semliki forest virus and that can be extrapolated to sketch tm helical packing in other alpha-viruses. molecular dynamics simulations were performed in wild-type and mutant peptides, both isolated and forming e1/e2 complexes. the simulations ...200314645057
targeting of adenovirus via genetic modification of the viral capsid combined with a protein bridge.a potential barrier to the development of genetically targeted adenovirus (ad) vectors for cell-specific delivery of gene therapeutics lies in the fact that several types of targeting protein ligands require posttranslational modifications, such as the formation of disulfide bonds, which are not available to ad capsid proteins due to their nuclear localization during assembly of the virion. to overcome this problem, we developed a new targeting strategy, which combines genetic modifications of t ...200314645549
functional analysis of nsp3 phosphoprotein mutants of sindbis virus.alphavirus nsp3 phosphoprotein is essential for virus replication and functions initially within polyprotein p123 or p23 components of the short-lived minus-strand replicase, and upon polyprotein cleavage, mature nsp3 likely functions also in plus-strand synthesis. we report the identification of a second nsp3 mutant from among the a complementation group of sindbis virus (sin) heat-resistant strain, ts rna-negative mutants. the ts138 mutant possessed a change of g4303 to c, predicting an ala68- ...200314645567
infection and injury of neurons by west nile encephalitis virus.west nile virus (wnv) infects neurons and leads to encephalitis, paralysis, and death in humans, animals, and birds. we investigated the mechanism by which neuronal injury occurs after wnv infection. neurons in the anterior horn of the spinal cords of paralyzed mice exhibited a high degree of wnv infection, leukocyte infiltration, and degeneration. because it was difficult to distinguish whether neuronal injury was caused by viral infection or by the immune system response, a novel tissue cultur ...200314645577
reactive oxygen species formation by uv-a irradiation of urocanic acid and the role of trace metals in this chemistry.we have extended our study of the decomposition of urocanic acid (uca) with ultraviolet a radiation (uv-a) by the self-sensitized generation of singlet oxygen (see photochem. photobiol. 75, 565 [2002]). the chemistry has been found to be partially dependent on the presence of trace metal, most likely iron. rigorous removal of metal impurities from the reaction mixture, using chelex, retarded (but did not eliminate) the uv-a-initiated uca degradation. the addition of small amounts of ferric chlor ...200314743864
study of caspase inhibitors for limiting death in mammalian cell culture.apoptosis in mammalian cell culture is associated with decreased bioproduct yields and can be inhibited through altering the intracellular signaling pathways mediating programmed cell death. in this study, we evaluated the capacity to inhibit caspases to maintain high viable cell numbers in cho and 293 cultures. two genetic caspase inhibitors, xiap and crma, were examined along with a mutant of each, xiap-bir123nc, which contains three bir domains but lacks the ring finger, and crma-dqmd, which ...200312474256
transcription strategy in a closterovirus: a novel 5'-proximal controller element of citrus tristeza virus produces 5'- and 3'-terminal subgenomic rnas and differs from 3' open reading frame controller elements.citrus tristeza virus (ctv) produces more than thirty 3'- or 5'-terminal subgenomic rnas (sgrnas) that accumulate to various extents during replication in protoplasts and plants. among the most unusual species are two abundant populations of small 5'-terminal sgrnas of approximately 800 nucleotides (nt) termed low-molecular-weight tristeza (lmt1 and lmt2) rnas. remarkably, ctv replicons with all 10 3' genes deleted produce only the larger lmt1 rnas. these 5'-terminal positive-sense sgrnas do not ...200312477839
poliovirus-induced apoptosis is reduced in cells expressing a mutant cd155 selected during persistent poliovirus infection in neuroblastoma cells.poliovirus (pv) can establish persistent infections in human neuroblastoma imr-32 cells. we previously showed that during persistent infection, specific mutations were selected in the first extracellular domain of the pv receptor (cd155) of these cells (n. pavio, t. couderc, s. girard, j. y. sgro, b. blondel, and f. colbère-garapin, virology 274:331-342, 2000). these mutations included the ala 67 --> thr substitution, corresponding to a previously described allelic form of the pv receptor. the m ...200312477887
small interfering rna-mediated inhibition of hepatitis c virus replication in the human hepatoma cell line huh-7. 200312477890
enhanced immunogenicity to mycobacterium tuberculosis by vaccination with an alphavirus plasmid replicon expressing antigen 85a.the immunogenicity of a plasmid dna vaccine incorporating sindbis virus rna replicase functions (psincp) and expressing antigen 85a (ag85a) from mycobacterium tuberculosis was compared with a conventional plasmid dna vector encoding ag85a. psincp-85a was highly immunogenic in mice and gave enhanced long-term protection against m. tuberculosis compared with the conventional vector.200312496215
alphavirus-based dna vaccine breaks immunological tolerance by activating innate antiviral pathways.cancer vaccines targeting 'self' antigens that are expressed at consistently high levels by tumor cells are potentially useful in immunotherapy, but immunological tolerance may block their function. here, we describe a novel, naked dna vaccine encoding an alphavirus replicon (self-replicating mrna) and the self/tumor antigen tyrosinase-related protein-1. unlike conventional dna vaccines, this vaccine can break tolerance and provide immunity to melanoma. the vaccine mediates production of double- ...200312496961
antiviral effect and virus-host interactions in response to alpha interferon, gamma interferon, poly(i)-poly(c), tumor necrosis factor alpha, and ribavirin in hepatitis c virus subgenomic replicons.the recently developed hepatitis c virus (hcv) subgenomic replicon system was utilized to evaluate the efficacy of several known antiviral agents. cell lines that persistently maintained a genotype 1b replicon were selected. the replicon resident in each cell line had acquired adaptive mutations in the ns5a region that increased colony-forming efficiency, and some replicons had acquired ns3 mutations that alone did not enhance colony-forming efficiency but were synergistic with ns5a mutations. a ...200312502825
an attenuating mutation in nsp1 of the sindbis-group virus s.a.ar86 accelerates nonstructural protein processing and up-regulates viral 26s rna synthesis.the sindbis-group alphavirus s.a.ar86 encodes a threonine at nonstructural protein 1 (nsp1) 538 that is associated with neurovirulence in adult mice. mutation of the nsp1 538 thr to the consensus ile found in nonneurovirulent sindbis-group alphaviruses attenuates s.a.ar86 for adult mouse neurovirulence, while introduction of thr at position 538 in a nonneurovirulent sindbis virus background confers increased neurovirulence (m. t. heise et al., j. virol. 74:4207-4213, 2000). since changes in the ...200312502831
glycosaminoglycan binding properties of natural venezuelan equine encephalitis virus isolates.equine-virulent, epidemic/epizootic strains of venezuelan equine encephalitis (vee) virus (veev) arise via mutation of progenitor enzootic strains that replicate poorly in equines. sequencing studies have implicated positively charged amino acids on the surface of the e2 envelope glycoprotein in the acquisition of equine virulence and viremia potential, suggesting that changes in binding to cell surface glycosaminoglycans (gags) may mediate vee emergence. therefore, we evaluated the binding of n ...200312502837
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