Publications

host-dependent evolution of the sindbis virus promoter for subgenomic mrna synthesis.	alphaviruses are alternately transmitted between arthropod and vertebrate hosts. in each host, the virus transcribes a subgenomic mrna that encodes the viral structural proteins which encapsidate the genome to form progeny virions. transcription initiates at an internal site called the promoter. to determine if promoter utilization varies in mammalian versus mosquito cells, we used these cells as hosts to select for active promoters among a library of different mutant promoters. compared with th ...	1995	7494288
the expression of chloramphenicol acetyltransferase in mosquitoes and mosquito cells using a packaged sindbis replicon system.	sindbis (sin) replicon virus was used to express chloramphenicol acetyltransferase (cat) in aedes albopictus (c6/36) cells and aedes triseriatus mosquitoes. rna transcribed in vitro from a sin replicon plasmid (psinrep5/cat) and from sin virus helper constructs (pdh-eb or pdh(26s)5'sin) was coelectroporated into bhk-21 cells to generate replicon viruses, designated rep5/cat/eb and rep5/cat/26s. c6/36 cells infected with rep5/cat/eb or rep5/cat/26s virus at a multiplicity of infection of 3, expre ...	1995	7498436
nucleocapsid and glycoprotein organization in an enveloped virus.	alphaviruses are a group of icosahedral, positive-strand rna, enveloped viruses. the membrane bilayer, which surrounds the approximately 400 a diameter nucleocapsid, is penetrated by 80 spikes arranged in a t = 4 lattice. each spike is a trimer of heterodimers consisting of glycoproteins e1 and e2. cryoelectron microscopy and image reconstruction of ross river virus showed that the t = 4 quaternary structure of the nucleocapsid consists of pentamer and hexamer clusters of the capsid protein, but ...	1995	7867069
isolation of the anthropogenic compound fluoranthene in a screening of chinese medicinal plants for antiviral compounds.	thirty-one species of medicinal plants used in the treatment of diseases of viral origin in yunnan province of china were assayed for inhibition of sindbis and murine cytomegalovirus in mammalian cell cultures. sixteen species displayed antiviral activity. a compound, which exhibited long wavelength uv-mediated antiviral activity, was isolated from leaves and twigs of elsholtzia ciliata (lamiaceae) using bioassay-guided fractionation and identified as the polycyclic aromatic hydrocarbon, fluoran ...	1995	7753931
a sindbis virus mrna polynucleotide vector achieves prolonged and high level heterologous gene expression in vivo.	the direct intramuscular delivery of naked plasmid dna has been demonstrated to allow expression of encoded heterologous genes in the target myocytes. the method has been employed to elicit immunization based upon delivery of antigen encoding plasmid dna. for application in the context of achieving anti-tumor immunization against antigenic transforming oncoproteins, delivery of plasmid dnas encoding these molecules would create significant potential safety hazards. as an alternative to dna polyn ...	1995	7784202
assessment of fusogenic properties of influenza virus hemagglutinin deacylated by site-directed mutagenesis and hydroxylamine treatment.	influenza virus hemagglutinin (ha) subtype h7 expressed from a baculovirus vector in insect cells requires cysteine residues for palmitoylation. mutant ha devoid of fatty acids shows hemagglutinating and hemolytic activities almost identical to those of the acylated wild-type ha (wt). using a membrane mixing assay (r18), neither the kinetics nor the ph dependence of fusion induced by wt or mutant ha was significantly different from virus-induced fusion. ha-induced fusion of insect cells with hum ...	1995	7793071
a pseudo-revertant of a sindbis virus 6k protein mutant, which corrects for aberrant particle formation, contains two new mutations that map to the ectodomain of the e2 glycoprotein.	most site-directed mutations in the gene encoding the small, membrane-associated 6k protein of sindbis virus interfere selectively with virus assembly and budding. particles are released that are aberrant in structure, with a single membrane enclosing multiple nucleocapsids. a revertant for the mutation that inserted a serine for a cysteine at position 39 in the 6k protein was isolated and found to correct for the defective budding so that normal particles were formed. genetic analysis of this r ...	1995	7856077
molecular genetic manipulation of mosquito vectors.	despite their central role in disease transmission, relatively little is known of the molecular biology of arthropod vectors. modern molecular approaches will undoubtedly provide considerable information about gene regulation and expression in vectors and consequently a much better understanding of the biology and molecular biology of vectors. such knowledge is essential for developing effective control strategies for vector-borne diseases. in this review, we focus upon techniques and approaches ...	1995	7810990
involvement of the molecular chaperone bip in maturation of sindbis virus envelope glycoproteins.	sindbis virus codes for two membrane glycoproteins, e1 and pe2, which assemble into heterodimers within the endoplasmic reticulum. we have examined the role of the molecular chaperone bip (grp78) in the maturation of these two proteins. e1, which folds into its mature conformation via at least three intermediates differing in the configurations of their disulfide bonds, was found to interact strongly and transiently with bip after synthesis. atp depletion mediated by carbonyl cyanide m-chlorophe ...	1995	7853497
a plasmid-based self-amplifying sindbis virus vector.	sindbis virus was used as a self-amplifying eukaryotic expression vector. a recombinant cdna genome of this (+)-strand rna virus was placed under the transcriptional control of a rous sarcoma virus ltr (rsv) promoter. transfection of this plasmid construct into mammalian cell lines (3t3, hepg2, and 293 cells) resulted in expression of the luciferase reporter gene. high-expression levels were also measured after transfection into primary rat myoblasts. in differentiated myotubes, expression level ...	1995	8527474
layered amplification of gene expression with a dna gene delivery system.		1995	8546403
thiol agents and bcl-2 identify an alphavirus-induced apoptotic pathway that requires activation of the transcription factor nf-kappa b.	oxidative stress has been proposed as a common mediator of apoptotic death. to investigate further the role of oxidants in this process we have studied the effects of antioxidants on sindbis virus (sv)-induced apoptosis in two cell lines, at-3 (a prostate carcinoma line) and n18 (a neuroblastoma line). the thiol antioxidant, n-acetylcysteine (nac), at concentrations above 30 mm, completely abrogates sv-induced apoptosis in at-3 and n18 cells. the effects of nac cannot be attributed to inhibition ...	1995	8522579
replication and expression of a recombinant sindbis virus in mosquitoes.	a recombinant sindbis virus, te/3'2j/anti-s, containing lacrosse virus small segment cdna in antisense orientation, was inoculated into aedes triseriatus mosquitoes. virus replication and lac-anti-s rna expression were analysed temporally and spatially. te/3'2j/anti-s virus titre peaked at 5.0 log10 tcid50 in heads 6-9 days post infection (p.i.) and decreased to 3.4 log10 tcid50 by 37 days p.i. salivary glands contained 4.4 log10 tcid50 of virus 6 days p.i.; titres were lower in other organs. la ...	1995	8825762
[concentrate of coagulation factor ix: viral validation of the thermoinactivation process].	the coagulation factor ix obtained at the institute of haematology and transfusion in warsaw was subjected to virological validation. two lipide enveloped viruses were used: hsv-1 and sindbis which may be a model for the viruses of b and c types in hepatitis. it was shown that heating of the freeze-drying preparations at 80 degrees c during 72 hrs leads to full inactivation of the added model viruses.	1995	8571744
[viral validation of the bio-globulin production process].	intravenous human immunoglobulin of domestic production was subjected to validation studies. tests were performed in the system of model viruses for pathogenic factors of the b and c types of hepatitis. for simulated immunoglobulin infections two lipid-enveloped viruses were chosen: the first dna virus pseudorabies pr-75 (model for hbv) and the second-rna virus sindbis (model for hcv). the survival of viruses in particular stages of bio-globulin production was checked, showing that pepsin digest ...	1995	8523973
laboratory transmission of sindbis virus by aedes albopictus, ae. aegypti, and culex pipiens (diptera: culicidae).	the susceptibility of aedes albopictus (skuse) for sindbis (sin) virus was examined in the laboratory. ae. albopictus, ae. aegypti (l.), and culex pipiens (l.) became infected with and subsequently transmitted sin virus by bite to chicks after feeding on viremic 1-d-old chicks. after ingesting 10(5.3) plaque-forming units (pfu)/ml, ae. albopictus had the highest transmission rate (30%) of the 3 species. transmission by ae. aegypti was less efficient (7%), whereas none of the cx. pipiens transmit ...	1995	8551504
characterization of revertants of a sindbis virus 6k gene mutant that affects proteolytic processing and virus assembly.	alphaviruses of the togaviridae encode a small hydrophobic polypeptide of 55 amino acids, noted as the 6k protein, that is synthesized as part of a polyprotein containing the sequences of the two major transmembranal viral structural glycoproteins. mutations, insertions and deletions in the 6k appear to selectively interfere with the final stages of virus assembly and budding, producing aberrant, multi-cored infectious viruses. in addition, some of these mutations were pleiotropic and much more ...	1995	8837882
[analysis of the primary structure of segments of the karelian fever virus genome].	primary structure of two parts of karelian fever virus (kfv) genome (29-57 nt and 10507-11591 nt) cloned in recombinant plasmids has been studied and compared with that of sindbis (hrsp strain) and ockelbo viruses. fifty-four nucleotide substitutes were revealed in the sequenced parts of kfv genome including partially 5' and 3'-nontranslated sites ( a total of 1613 nucleotides, or approximately 13.8% of the genome length), in comparison with the sindbis virus prototype hrsp strain, this being in ...	1995	8659171
inactivation of the small gtp binding protein rho induces multinucleate cell formation and apoptosis in murine t lymphoma el4.	the small g-protein rho regulates the actin microfilament-dependent cytoskeleton. exoenzyme c3 of clostridium botulinum adp-ribosylates rho at asn41, a modification that functionally inactivates rho. using a sindbis virus-based transient gene expression system, we studied the role of rho in murine el4 t lymphoma cells. we generated a double subgenomic infectious sindbis virus (dssin:c3) recombinant which expressed c3 in >95% of el4 cells. this intracellular c3 resulted in modification and inacti ...	1996	8666781
[comparative analysis of primary structure of nucleocapsid protein from western equine encephalomyelitis virus and other alphaviruses].	part of wee virus (strain 16310-5614) genome coding for the nucleocapsid (c) protein was cloned and sequenced in two independent clones. the c gene of wee virus is composed of 77 nucleotides, both for the bfs and 16310 strains, and is 48, 24, 33, 15, 3, and 3 nucleotides shorter than that of venezuelan equine encephalomyelitis (vee), semliki forest, ross river, sindbis, o'nyong-nyong, and eastern equine encephalomyelitis (eee) viruses, respectively. it contains 16 nucleotide changes in compariso ...	1996	8999681
[comparative evaluation of test-systems for detection of venezuelan equine encephalomyelitis virus and variola virus using dot immunoenzyme assay and solid-phase lanthanide immunofluorescent assay].	the sensitivity and specificity of 4 experimental test systems for dot enzyme immunoassay (dot-eia) and solid-phase lanthanide immunofluorescent analysis (sp lifa) were studied with venezuelan equine encephalomyelitis (vee) and variolovaccinia viruses. test systems for sp lifa proved to be 25 times more sensitive than those for dot-eia. the test systems were highly specific and did not react with the heterologous viruses and proteins. diagnostic agent for detecting vee virus in dot-eia was false ...	1996	8999688
expression of parvovirus luiii ns1 from a sindbis replicon for production of luiii-luciferase transducing virus.	in order to develop an alternative packaging system for recombinant parvoviruses, the gene for the major nonstructural protein (ns1) of parvovirus luiii was inserted into a sindbis replicon vector. cells infected with recombinant sinns1 virus produced ns1 rna from the sindbis 26s promoter and expressed ns1 protein which was able to transactivate a parvovirus p38 promoter. co-transfections of sindbis-ns1 rna together with a packageable luiii transducing genome and a coat protein expression plasmi ...	1996	9029782
the gordon wilson lecture: unique interactions between viruses, neurons and the immune system.	the increased susceptibility of young individuals to alphavirus encephalitis is likely to be linked to the ease with which immature neurons are induced to undergo apoptosis after infection. in the more mature individuals, virus infection of neurons may not lead to apoptosis and in the absence of an effective immune response persistent infection is established. the major mechanism by which alphavirus infection of neurons is controlled is by production and local secretion of antibody to the surfac ...	1996	8725563
antiviral activities of medicinal plants of southern nepal.	in a screening of plants used traditionally in nepal to treat diseases that could be caused by viruses, twenty-one methanol extracts from twenty species were quantitatively assayed for activity against three mammalian viruses: herpes simplex virus, sindbis virus and poliovirus. assays were performed in ultraviolet (uv)-a or visible light, as well as dark, and cytotoxicity was also noted. impressive antiviral activities were exhibited by species of bauhinia (fabaceae), carissa (apocynaceae), mill ...	1996	8844464
neutralizing antibody to human rhinovirus 14 penetrates the receptor-binding canyon.	the three-dimensional structure of intact human rhinovirus 14 (hrv-14) complexed with fab fragments (fab17-ia) from a strongly neutralizing antibody that binds bivalently to the virion has been determined to 4.0 angstrom resolution by a combination of x-ray crystallography and cryo-electron microscopy. in contradiction to the most commonly held model of antibody-mediated neutralization, fab17-ia does not induce a conformational change in the hrv-14 capsid. instead, the paratope of the antibody u ...	1996	8848050
fatal sindbis virus infection of neonatal mice in the absence of encephalitis.	a comparative pathogenesis study was performed in neonatal mice using a molecularly cloned laboratory variant of sindbis strain ar339, designated trsb, and a single-site attenuated mutant of trsb derived by site-directed mutagenesis of the e2 glycoprotein from ser to arg at residue 114 (trsbr114). trsb caused 100% mortality with an average survival time of 3.0 +/- 0.7 days, whereas mice inoculated with trsbr114 exhibited an attenuated disease course with 46% mortality and an extended average sur ...	1996	8862401
mosquito homolog of the la autoantigen binds to sindbis virus rna.	we have isolated a 50-kda mosquito protein that binds with high affinity to a riboprobe representing the 3' end of the minus strand of sindbis virus rna. the isolated protein has been used to obtain cdna clones encoding this protein that have been sequenced and used to express the protein in large amounts. sequence comparisons make clear that this protein is the mosquito homolog of the la autoantigen. the n-terminal half of the protein shares considerable sequence identity with the human la prot ...	1996	8551578
translation of sindbis virus mrna: analysis of sequences downstream of the initiating aug codon that enhance translation.	alphaviruses, particularly sinbis virus and semliki forest virus, are proving to be useful vectors for the expression of heterologous genes. in infected cells, these self-replicating vectors (replicons) transcribe a subgenomic mrna that codes for a heterologous protein instead of the structural proteins. we reported recently that translation of the reporter gene lacz is enhanced 10-fold when the coding sequences of this gene are fused downstream of and in frame with the 5' half of the capsid gen ...	1996	8551579
events in the endoplasmic reticulum abrogate the temperature sensitivity of sindbis virus mutant ts23.	temperature-sensitive mutations in proteins produced at or heated to a nonpermissive temperature render the proteins defective in some aspect of their maturation into functional entities. the characterization of temperature-sensitive mutations in model proteins, such as virus membrane proteins, has allowed the elucidation of critical events in the maturation of virus membranes as well as in the intracellular folding, processing, and transport of membrane proteins in general. we have used a trans ...	1996	8551635
regulation of lymphocyte homing into the brain during viral encephalitis at various stages of infection.	the passage of circulating lymphocytes into the central nervous system (cns) during acute viral encephalitis was studied in vivo using fluorescently labeled cells inoculated into sindbis virus (sv)-infected mice. donor lymphocytes were detected in the brains of recipient animals when mononuclear cells were isolated from the cns and screened by flow cytometry. the magnitude of this accumulation related to the duration of encephalitis in recipient mice and to the activation state of the inoculated ...	1996	8621923
bax-independent inhibition of apoptosis by bcl-xl.	the bcl-2-related protein, bcl-xl, has been shown to block apoptosis induced by a variety of stimuli and to be a stronger protector against apoptosis than bcl-2 under certain circumstances. using site-specific mutagenesis, we show here that the amino-acid residues critical for protection of cells by bcl-xl against sindbis virus-induced apoptosis are clustered within the bcl-2-homology regions 1 and 2 (bh1 and bh2 regions). the residues necessary for bcl-xl function are not identical to those req ...	1996	8596636
inhibition of na+k+atpase activity in membranes of sindbis virus-infected chick cells.	alterations in intracellular concentrations of na+ and k+ in sindbis virus-infected cells result largely from inhibition of ouabain-sensitive na+k+atpase (na+ pump) activity. here we report that membrane preparations derived from sindbis virus-infected chick cells exhibit reduced na+k+atpase activity, indicating that limitation of cellular factors is not responsible for inhibition of ion transport. in vitro phosphorylation of the na+k+atpase by [32p]orthophosphate or [gamma 32p]atp is unaltered ...	1996	8607259
mutagenesis of the sindbis virus nsp1 protein: effects on methyltransferase activity and viral infectivity.	it has been suggested that four amino acids which are absolutely conserved in th nsp1 nonstructural proteins encoded by togaviruses and in the homologous proteins encoded by plant viruses in the sindbis virus (sv) superfamily may constitute a "methyltransferase motif." in the sindbis virus nsp1 protein (540 amino acids) these four amino acids are represented by his39, arg91, asp94, and tyr249. earlier, in assays of methyltransferase (mtase) activity generated in sv-infected cells, we had shown t ...	1996	8610444
assembly of the sindbis virus spike protein complex.	the sindbis virus glycoproteins e1 and e2 are organized into 80 trimers of heterodimers within the virus envelope. using pulse-chase protocols and chemical crosslinkers, we have found that e1 and e2 precursor, pe2, rapidly assemble into heterodimers and then into trimers of heterodimers after translocation into the endoplasmic reticulum. e1 folds into its mature conformation within the endoplasmic reticulum via at least three intermediates differing in the configurations of their disulfide bonds ...	1996	8623521
alphavirus-induced apoptosis in mouse brains correlates with neurovirulence.	sindbis virus induces apoptotic cell death in cultured cell lines, raising the possibility that apoptosis of infected neurons and other target cells in vivo may contribute to the resulting disease and mortality. to investigate the role of apoptosis in sindbis virus pathogenesis, infected mouse brains were assayed by the in situ terminal deoxynucleotidyltransferase-mediated dutp nick end-labeling technique and for dna ladder formation. infection with recombinant sindbis virus strain 633 resulted ...	1996	8627707
deduced consensus sequence of sindbis virus strain ar339: mutations contained in laboratory strains which affect cell culture and in vivo phenotypes.	the consensus sequence of the sindbis virus ar339 isolate, the prototype alphavirus, has been deduced. the results presented here suggest (i) that a substantial proportion of the sequence divergence evident between the consensus sequence and sequences of laboratory strains of ar339 has resulted from selection for efficient growth in cell culture, (ii) that many of these changes affect the virulence of the virus in animal models, and (iii) that such modified genetic backgrounds present in laborat ...	1996	8627724
differential processing of sindbis virus glycoprotein pe2 in cultured vertebrate and arthropod cells.	a step in the maturation of sindbis virus glycoproteins is the cleavage of the precursor glycoprotein pe2 into e3 and e2 by furin or a furin-like host cell protease. the results presented here suggest that pe2 cleavage is an obligatory event for sindbis virus maturation in c6/36 cells and demonstrate that certain mutants display a cell-specific pe2 cleavage phenotype. we previously have described sindbis virus variants which fail to cleave pe2 because of incorporation of a signal for n-linked gl ...	1996	8627739
sindbis virus rna-negative mutants that fail to convert from minus-strand to plus-strand synthesis: role of the nsp2 protein.	we identified mutations in the gene for nsp2, a nonstructural protein of the alphavirus sindbis virus, that appear to block the conversion of the initial, short-lived minus-strand replicase complex (rcinitial) into mature, stable forms that are replicase and transcriptase complexes (rcstable), producing 49s genome or 26s mrna. base changes at nucleotide (nt) 2166 (g-->a, predicting a change of glu-163-->lys), at nt 2502 (g-->a, predicting a change of val-275-->ile), and at nt 2926 (c-->u, predic ...	1996	8627744
identification of a region in the sindbis virus nucleocapsid protein that is involved in specificity of rna encapsidation.	the specific encapsidation of genomic rna by an alphavirus requires recognition of the viral rna by the nucleocapsid protein. in an effort to identify individual residues of the sindbis virus nucleocapsid protein which are essential for this recognition event, a molecular genetic analysis of a domain of the protein previously suggested to be involved in rna binding in vitro was undertaken. the experiments presented describe the generation of a panel of viruses which contain mutations in residues ...	1996	8627749
dengue hemorrhagic fever.		1996	8629013
efficiency of transduction by recombinant sindbis replicon virus varies among cell lines, including mosquito cells and rat sensory neurons.	recombinant alphaviruses have been used as vehicles for delivery and expression of heterologous genes in mammalian, avian and insect cell lines. we have used a sindbis replicon virus (sinreplac) able to express the e. coli lacz gene to compare the efficiency of transduction in one insect, six mammalian cell lines and cultured rat dorsal neurons which apparently express beta-galactosidase over a 30-day time period. results show that different cell lines were transduced with varying degrees of eff ...	1996	8879590
an eruption associated with alphavirus infection.	some alphaviruses, e.g. sindbis, cause an acute febrile illness associated with papular rashes and arthralgia. the diagnosis is usually serological and, hence, the histopathology of the rashes has been poorly elucidated. we report on two patients with rapidly healing eruptions associated with sindbis virus infection. the histopathology of the rashes showed large, pronounced lymphohistiocytic infiltrates with atypical lymphoid cells around the hair follicles, changes not usually seen in rapidly-h ...	1996	8881685
alphavirus infection in mosquitoes at the ross river reservoir, north queensland, 1990-1993.	this study addresses the potential problem of alphavirus infection associated with recreational use of the ross river reservoir in north queensland, australia. from 1990 to 1993, 51,497 adult female mosquitoes were collected mainly by co2-supplemented light traps. four localities within the reservoir were considered and compared with mosquitoes collected during 1991 from 2 public localities around townsville city. ten isolates of ross river virus, one of barmah forest virus, and 2 of sindbis vir ...	1996	8887221
dominant inhibitory ras delays sindbis virus-induced apoptosis in neuronal cells.	mature neurons are more resistant than dividing cells or differentiating neurons to sindbis virus-induced apoptotic death. therefore, we hypothesized that mitogenic signal transduction pathways may influence susceptibility to sindbis virus-induced apoptosis. since ras, a 21-kda gtp-binding protein, plays an important role in cellular proliferation and neuronal differentiation, we investigated the effect of an inducible dominant inhibitory ras on sindbis virus-induced death of a rat pheochromocyt ...	1996	8892895
chimeric sindbis-ross river viruses to study interactions between alphavirus nonstructural and structural regions.	sindbis virus and ross river virus are alphaviruses whose nonstructural proteins share 64% identity and whose structural proteins share 48% identity. starting from full-length cdna clones of both viruses, we have generated two reciprocal sindbis-ross river chimeric viruses in which the structural and nonstructural regions have been exchanged. these chimeric viruses replicate readily in several cell lines. both chimeras grow more poorly than do the parental viruses, with the chimera containing si ...	1996	8892913
green fluorescent protein expressed in living mosquitoes--without the requirement of transformation.	mosquitoes transmit viruses, protozoa and nematodes that are major causes of morbidity and mortality in humans. details of arthropod anatomy and development, and the replication and development of pathogens in the arthropod vector, have relied upon examination of dissected or histologically processed material. we constructed a double-subgenomic sindbis (dssin) virus expressing green fluorescent protein to demonstrate the potential of this protein for studying pathogen development in living arthr ...	1996	8891217
interactions between pe2, e1, and 6k required for assembly of alphaviruses studied with chimeric viruses.	during the assembly of alphaviruses, a preassembled nucleocapsid buds through the cell plasma membrane to acquire an envelope containing two virally encoded glycoproteins, e2 and e1. using two chimeric viruses, we have studied interactions between e1, e2, and a viral peptide called 6k, which are required for budding. a chimeric sindbis virus (sin) in which the 6k gene had been replaced with that from ross river virus (rr) produced wild-type levels of nucleocapsids and abundant pe2/e1 heterodimer ...	1996	8892914
evidence of vertical transmission of ross river and sindbis viruses (togaviridae: alphavirus) by mosquitoes (diptera: culicidae) in southeastern australia.	ross river and sindbis viruses were isolated from aedes camptorhynchus adults reared from immatures collected from a salt marsh in coastal victoria, indicating the existence of field vertical transmission. these first isolations of an arbovirus from adult mosquitoes reared from field-collected immatures in australia indicates one mechanism for arbovirus maintenance in temperate regions.	1996	8906927
[sindbis viruses of various geographic origin and differentiation of them from western equine encephalomyelitis viruses using the polymerase chain reaction].	comparison of sindbis virus strains isolated in different regions of the world (in africa, australia, and europe, including russia and its nearest neighbors) in the polymerase chain reaction (pcr) by the primary gene structure of proteins nsp1 and e1 and in the neutralization test showed the greatest similarity between geographically close strains isolated in northern europe (kfl, karelia, 1381 and 1388, estonia). sindbis strains ar339 and babanki isolated in africa were similar to each other an ...	1996	8928504
sindbis virus vectors for expression in animal cells.	sindbis virus and other alphavirus gene expression vectors have recently been used to express and study the functions of proteins and rna, to evaluate classical vaccine and novel antiviral approaches, and for nucleic acid immunization. the vectors will likely attract continuing, innovative applications that exploit their useful features: rapid and efficient gene expression, wide host range, and rna genomes.	1996	8939619
low ph-induced pore formation by spike proteins of enveloped viruses.	exposure of aedes albopictus cells infected with semliki forest virus (sfv; togaviridae) to mildly acidic ph (5.6) results in a dramatic increase in the host cell membrane permeability due to pore formation by the virus spike proteins. identical results were obtained when the cells were infected with two other viruses, sindbis virus (sin, togaviridae) and vesicular stomatitis virus (vsv, rhabdoviridae). this permeability change could also be observed on isolated virions of sfv, sin and vsv by me ...	1996	9000093
the polarity of the plasma membrane protein ret-pe2 in retinal pigment epithelium is developmentally regulated.	the retinal pigment epithelium (rpe) differs from other epithelia in that the apical surface is not free; instead, it interacts with both photoreceptors and a specialized extracellular material, the interphotoreceptor matrix. biochemical characterization of the apical and basolateral surfaces of rpe in adult rat eye cups, using a novel in situ biotinylation assay, revealed very different protein compositions and identified a major surface antigen, ret-pe2, with a predominantly apical distributio ...	1996	9004037
[comparative study of the mechanism of inhibition of sindbis virus reproduction by adamantane derivatives: remantadine and amide of 1-adamantane carboxylic acid].	amide of 1-adamantane carboxylic acid (aaca), the same as remantadine, was shown to have no antiviral action and any influence on the efficiency of the sindbis virus adsorption. however, it significantly inhibited the virus specific synthesis of rna and protein. the main difference between aaca and remantadine was in the fact that the efficiency of the inhibition of the sindbis virus reproduction and synthesis of the virus specific rna in the presence of aaca did not markedly decrease even when ...	1996	8999758
molecularly engineered resistance to california serogroup virus replication in mosquito cells and mosquitoes.	introduction of genetic elements derived from a viral pathogen's genome may be used to reduce the vectorial capacity of mosquitoes for that virus. a double subgenomic sindbis virus expression system was utilized to transcribe sequences of lacrosse (lac) virus small (s) or medium (m) segment rna in sense or antisense orientation; wild-type sindbis and lacrosse viruses have single-stranded rna genomes, the former being positive sense and the latter being negative sense. recombinant viruses were ge ...	1996	8633038
pathogen-derived resistance to dengue type 2 virus in mosquito cells by expression of the premembrane coding region of the viral genome.	the full-length premembrane (prm) coding region of the dengue virus type 2 (den-2; jamaica) genome was expressed in c6/36 (aedes albopictus) cells in either the sense or the antisense orientation from a double subgenomic sindbis (dssin) virus. northern (rna) blot analysis confirmed the expression of sense or antisense den-2 prm rna in infected c6/36 cells. prm protein was demonstrated in cells infected with dssin virus expressing den-2 sense rnas by an immunofluorescence assay. c6/36 cells were ...	1996	8642634
temporal changes in chromatin, intracellular calcium, and poly(adp-ribose) polymerase during sindbis virus-induced apoptosis of neuroblastoma cells.	sindbis virus (sv) induces apoptosis in many vertebrate cells, but the mechanism is unknown. to gain insight into this mechanism, the nature and time course of intracellular changes related to programmed cell death were studied in sv-infected mouse neuroblastoma cells. new virus production began at 5 h after infection and reach a peak at 12 h. hoechst 33342 staining of dna analyzed by flow cytometry demonstrated changes in chromatin beginning 6 h after infection. these chromatin changes were cel ...	1996	8642645
bc1-2 protects mice against fatal alphavirus encephalitis.	virus-induced apoptosis has been well characterized in vitro, but the role of apoptosis in viral pathogenesis is not well understood. the suicide of a cell in response to viral infection is postulated to be an important host defense for the organism, leading to a reduction in its total viral burden. however, virus-induced death of nonregenerating cells in the central nervous system may be detrimental to the host. therefore, to investigate the role of apoptosis in the pathogenesis of fatal enceph ...	1996	8643485
detection of immunoglobulin g to a sindbis-related virus by a membrane antigen enzyme immunoassay.	we determined the seroprevalence of a sindbis-related virus isolated for the first time in 1975 from ticks in south-east sicily and typed by gresikova et al. in 1978. an indirect enzyme immunoassay based on viral membrane antigen for coating microtiter strips was used for the detection of immunoglobulin g to the sindbis-related virus. the method appeared more sensitive than a similar enzyme immunoassay based on crude lysate antigen. comparison of the results obtained from sera tested both by mem ...	1996	8673858
characterization of the rubella virus nonstructural protease domain and its cleavage site.	the region of the rubella virus nonstructural open reading frame that contains the papain-like cysteine protease domain and its cleavage site was expressed with a sindbis virus vector. cys-1151 has previously been shown to be required for the activity of the protease (l. d. marr, c.-y. wang, and t. k frey, virology 198:586-592, 1994). here we show that his-1272 is also necessary for protease activity, consistent with the active site of the enzyme being composed of a catalytic dyad consisting of ...	1996	8676497
viral safety of a new highly purified factor viii (octate).	the inactivation of both transfusion-relevant and model viruses by modified pasteurisation (10 hours at 63 degrees c in solution) has been evaluated following the established guidelines of the eu cpmp ad hoc working party on biotechnology/pharmacy. this heat treatment was introduced into the manufacturing process of octavi, a very high purity factor viii concentrate stabilized only by von willebrand factor, in the presence of a proprietary mixture of low molecular weight stabilizers. both envelo ...	1996	8699169
alphavirus hybrid virion vaccines.		1996	8718580
arbovirus survey in china in recent ten years.		1996	8758350
aromatic interactions define the binding of the alphavirus spike to its nucleocapsid.	most enveloped viruses bud from infected cells by a process in which viral intracellular core components interact with cytoplasmic domains of transmembrane spike glycoproteins. we have demonstrated previously that a tyrosine motif in the cytoplasmic domain of the semliki forest virus (sfv) spike glycoprotein e2 is absolutely essential for budding. in contrast, hardly anything is known regarding which region of the capsid protein is involved in spike binding. therefore, the mechanism by which spi ...	1996	8736551
identification of a protein binding site on the surface of the alphavirus nucleocapsid and its implication in virus assembly.	many enveloped viruses exit cells by budding from the plasma membrane. the driving force for budding is the interaction of an inner protein nucleocapsid core with transmembrane glycoprotein spikes. the molecular details of this process are ill defined. alphaviruses, such as sindbis virus (sinv) and semliki forest virus (sfv), represent some of the simplest enveloped viruses and have been well characterized by structural, genetic and biochemical techniques. although a high-resolution structure of ...	1996	8736552
nonhomologous rna-rna recombination events at the 3' nontranslated region of the sindbis virus genome: hot spots and utilization of nonviral sequences.	the mechanism of rna-rna recombination at the 3' nontranslated region (3'ntr) of the sindbis virus (sin) genome was studied by using nonreplicative rna precursors. the 11.7-kb sin genome was transcribed in vitro as two nonoverlapping rna fragments. rna-1 contained the entire 11.4-kb protein coding sequence of sin and also carried an additional 1.8-kb nonviral sequence at its 3' end. rna-2 carried the remaining 0.26 or 0.3 kb of the sin genome containing the 3'ntr. transfection of these two fragm ...	1996	8764023
disulfide bridge-mediated folding of sindbis virus glycoproteins.	the sindbis virus envelope is composed of 80 e1-e2 (envelope glycoprotein) heterotrimers organized into an icosahedral protein lattice with t=4 symmetry. the structural integrity of the envelope protein lattice is maintained by e1-e1 interactions which are stabilized by intramolecular disulfide bonds. structural domains of the envelope proteins sustain the envelope's icosahedral lattice, while functional domains are responsible for virus attachment and membrane fusion. we have previously shown t ...	1996	8764067
synthesis and antiviral activity evaluation of some new aminoadamantane derivatives. 2.	the synthesis of some new aminoadamantane derivatives is described. the new compounds were evaluated against a wide range of viruses [influenza a h1n1, influenza a h2n2, influenza a h3n2, influenza b, parainfluenza 3, herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2), thymidine kinase-deficient (tk-) hsv-1, vaccinia, vesicular stomatitis, polio 1, coxsackie b4, sindbis, semliki forest, reo 1, varicella-zoster virus (vzv), tk- vzv, human cytomegalovirus (hcmv), and human immunodeficiency vir ...	1996	8765514
antiviral activities of nepalese medicinal plants.	in a screening of plants used traditionally in nepal to treat diseases that could be caused by viruses, methanol extracts from 21 species were assayed for activity against three mammalian viruses: herpes simplex virus, sindbis virus and poliovirus. assays were performed in uv-a or visible light, as well as dark. individual species of hypericum, lygodium, and maesa exhibited impressive antiviral activities, although their selective effects on the three viruses suggested that the antiviral ingredi ...	1996	8771457
interferon-gamma induced type i nitric oxide synthase activity inhibits viral replication in neurons.	type i nos expression increases in ob neurons during vsv infection. immunocytochemical staining of nb41a3 cells indicates constitutive expression of interferon (ifn)-gamma receptor and type i nos. ifn-gamma treatment of nb41a3 cells increased no production and type i nos protein. in vitro replication of vsv, polio virus type i, and herpes simplex virus type i (hsv-1) is significantly inhibited by ifn-gamma induced type i nos and antagonized by nos inhibitors. in contrast, while ifn-gamma treatme ...	1996	8784266
translational regulation of na,k-atpase alpha1 and beta1 polypeptide expression in epithelial cells.	to investigate the regulation of the na,k-atpase, we have studied the expression of the na,k-atpase polypeptides in several mammalian cell lines using the vaccinia virus/t7 rna polymerase expression system. infection of several fibroblast-like cell lines with viral recombinants containing the na,k-atpase alpha and beta isoforms, the glucose transporters, glut 1 and glut 4, or the capsid protein of the sindbis virus all result in the production of the appropriate protein products. however, all ep ...	1996	8798517
analyses of the role of structural changes in the regulation of uncoating and assembly of alphavirus cores.	in the late stages of alphavirus multiplication virus cores accumulate in the cytoplasm as stable structures, whereas they are unstable during the early stages of infection. three types of explanation can be put forward to understand this phenomenon: (1) a cellular uncoating process is active early which is inactivated later, (2) the core structure differs between stable cores which accumulate and labile cores which are dissociated, (3) both mechanisms cooperate. a model based exclusively on the ...	1996	8806493
mutations in the endo domain of sindbis virus glycoprotein e2 block phosphorylation, reorientation of the endo domain, and nucleocapsid binding.	exposure of the carboxyl terminus (endo domain) of sindbis virus membrane glycoprotein e2 to the cell cytoplasm is critical for the interaction of the nucleocapsid with viral envelope proteins in modified cell membranes. we have shown that the endo domain of pe2/e2 is initially translocated into membranes of the endoplasmic reticulum and subsequently drawn back into the cell cytoplasm during virus assembly. we suggested that phosphorylation of pe2/e2 might be responsible for the reorganization o ...	1996	8806503
complete nucleotide sequence and full-length cdna clone of s.a.ar86 a south african alphavirus related to sindbis.	s.a.ar86 and girdwood s.a., two south african sindbis-like arboviruses, are closely related antigenically to the swedish isolate, ockelbo82 [lundström, j. o., vene, s., saluzzo, j. f., and niklasson, b. (1993) am. j. trop. med. hyg. 49(5), 531-537]. each of these viruses is associated with human disease, and girdwood s.a. was isolated from a human case. in addition, s.a.ar86 is unique among sindbis-like viruses in that adult mice remain sensitive to lethal infection with s.a.ar86. the complete g ...	1996	8806532
virus validation studies of immunoglobulin preparations.	a validation study of the viral safety of a new polyvalent intravenous immunoglobulin (octagam) according to eu-guideline iii/8115/89-en and the requirements of the federal agency for sera and vaccines in germany was undertaken in may 1994. the following processing steps were analyzed: cohn-oncley fractionation, solvent/detergent (sd) treatment, ph 4 exposure, storage of the final product at low ph and immune neutralisation.	1996	8828948
structural analysis of sindbis virus capsid mutants involving assembly and catalysis.	sindbis virus core protein (scp) has been isolated from virus and crystallized. the x-ray crystallographic structure showed that the amino-terminal 113 residues appeared to be either disordered or truncated during crystallization and that the carboxy-terminal residues 114 to 264 had a chymotrypsin-like structure. the carboxy-terminal residues 106 to 264 and 106 to 266 of scp have now been expressed in escherichia coli. most crystal forms of the truncated proteins were isomorphous with those of t ...	1996	8831786
vector-borne viral diseases in sweden--a short review.	ockelbo disease, caused by a sindbis-related virus transmitted to man by mosquitoes, was first described in the central part of sweden in the 1960s as clusters of patients with fever, arthralgia and rash. an average annual rate of 30 cases was recorded in the 1980s but no cases have been diagnosed during the last few years. nephropathia epidemica (ne) characterized by fever, abdominal pain and renal dysfunction has been known to cause considerable morbidity in sweden during the last 60 years but ...	1996	8800805
travel-related vector-borne virus infections in germany.	laboratory diagnosis of imported, vector-borne virus diseases during a 22-month-period in munich, germany, is summarized. in 13/317 germans returning from the mediterranean with suspected sandfly fever, acute sandfly fever, serotype toscana, was confirmed serologically: 84.6% of the infections were acquired in italy. of 249 german tourists with febrile disease returning from the tropics, acute infection with dengue virus was diagnosed serologically in 26 (10.4%): most infections were acquired in ...	1996	8800806
genetic relatedness of sindbis virus strains from europe, middle east, and africa.	the relatedness of 40 strains of sindbis virus (sin) from europe, the middle east, and africa was investigated by limited sequencing within the gene encoding the e2 glycoprotein corresponding to amino acid residues 117 to 229 and encompassing one of the major neutralization epitopes. phylogenetic analyses using distance matrix and parsimonious methods identified two major genetic clusters of western sin strains, although the variability was less than that of the corresponding region for venezuel ...	1996	8806528
sindbis virus dna-based expression vectors: utility for in vitro and in vivo gene transfer.	several dna-based sindbis virus vectors were constructed to investigate the feasibility and potential applications for initiating the virus life cycle in cells transfected directly with plasmid dna. these vectors, when transfected into mammalian cells, have been used to produce virus, to express heterologous genes, and to produce infectious vector particles. this approach involved the conversion of a self-replicating vector rna (replicon) into a layered dna-based expression system. the first lay ...	1996	8523564
polyanion inhibitors of human immunodeficiency virus and other viruses. part 2. polymerized anionic surfactants derived from amino acids and dipeptides.	a series of new polyanions was synthesized via gamma-polymerization, in aqueous micellar solution, of omega-unsaturated anionic surfactants whose polar head was derived from amino acids or dipeptides. the obtained polyanions were evaluated for their activity against human immunodeficiency virus (hiv-1, hiv-2) and various other rna and dna viruses. all the test compounds proved active against hiv-1 and hiv-2, their 50% inhibitory concentration (ic50) being in the range of 0.04-7.5 micrograms/ml, ...	1996	8648602
inhibition of nitric oxide synthesis increases mortality in sindbis virus encephalitis.	sindbis virus (sv) is an alphavirus that causes acute encephalomyelitis in mice. the outcome is determined by the strain of virus and by the age and genetic background of the host. the mortality rates after infection with nsv, a neurovirulent strain of sv, were as follows v: 81% (17 of 21) in balb/cj mice; 20% (4 of 20) in balb/cbyj mice (p < 0.001); 100% in a/j, c57bl/6j, sjl, and dba mice; and 79% (11 of 14) in immunodeficient scid/cb17 mice. treatment with nomega-nitro-l-arginine methyl ester ...	1996	8648734
genetically engineered resistance to dengue-2 virus transmission in mosquitoes.	the control of arthropod-borne virus diseases such as dengue may ultimately require the genetic manipulation of mosquito vectors to disrupt virus transmission to human populations. to reduce the ability of mosquitoes to transmit dengue viruses, a recombinant sindbis virus was used to transduce female aedes aegypti with a 567-base antisense rna targeted to the premembrane coding region of dengue type 2 (den-2) virus. the transduced mosquitoes were unable to support replication of den-2 virus in t ...	1996	8629025
effect of e2 envelope glycoprotein cytoplasmic domain mutations on sindbis virus pathogenesis.	the cytoplasmic domain of the e2 envelope glycoprotein is important in sindbis virus assembly, but little is known about its role in the pathogenesis of sindbis virus encephalitis. to investigate its role in viral pathogenesis, we constructed six recombinant viruses containing site mutations in the e2 cytoplasmic domain, using the neurovirulent background strain, te12. our findings demonstrate that the e2 cytoplasmic domain is a determinant of sindbis virus growth and neurovirulence in suckling ...	1996	8551591
antiviral activity of a derivative of the photosensitive compound hypericin.	eight synthetic compounds related to the photosensitive antiviral quinonic plant compound hypericin were screened for light-mediated antiviral activity. the compound 2,5,9,12-tetra(carboxyethylthiomethyl) hypericin was found to have activity against membrane-enveloped sindbis virus and murine cytomegalovirus but not against the non-enveloped poliovirus. the activity of this compound was investigated in more detail. the mechanism of action appeared to be of the photosensitive singlet oxygen type ...	1996	23194968
bcl-2 inhibits apoptosis and extends recombinant protein production in cells infected with sindbis viral vectors.	viruses carrying foreign genes are often used for the production of recombinant proteins in mammalian cells and other eukaryotic expression systems. though high levels of gene expression are possible using viral vectors, the host cell generally responds to the infection by inducing apoptotic cell death within several days, abruptly ending protein production. it has recently been demonstrated, however, that apoptosis can be suppressed in virally infected cells using anti-apoptotic genes, such as ...	1996	22358927
a bcl-2 homolog encoded by kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with bax or bak.	the bcl-2 protein family is characterized by the ability to modulate cell death, and members of this family share two highly conserved domains called bcl-2 homology 1 (bh1) and 2 (bh2) which have been shown to be critical for the death-repressor activity of bcl-2 and bcl-xl. through sequence analysis we identified a novel viral bcl-2 homolog, designated ksbcl-2, from human herpesvirus 8 (hhv8) or kaposi sarcoma-associated herpesvirus. the overall amino acid sequence identity between ksbcl-2 and ...	1997	9012846
construction and characterization of a reovirus double temperature-sensitive mutant.	the infectious reovirus rna system was used to construct a mutant with two temperature-sensitive (ts) lesions in genome segments m2 and s2, respectively. the double mutant is about 300 times more ts than either of its parents, which are about 1,500 and 170 times more ts than their wild-type parent reovirus st3 strain dearing. at 39 degrees c the double mutant is essentially unable to multiply. in spite of its striking temperature sensitivity, the double mutant elicits the formation of significan ...	1997	9192650
monoclonal antibodies specific for semliki forest virus replicase protein nsp2.	a panel of monoclonal antibodies (mabs) was raised against semliki forest virus (sfv) nonstructural protein nsp2, which is a protease, an ntpase, a putative rna helicase, and a regulator of the synthesis of the subgenomic 26s mrna encoding the structural proteins. nsp2, used for immunization, was expressed as a histidine fusion protein in escherichia coli and purified by metal affinity chromatography. dot-blot assay, using a membrane fraction from sfv-infected cells as antigen, gave 33 positive ...	1997	9018056
complementation of and interference with sindbis virus replication by full-length and deleted forms of the nonstructural protein, nsp1, expressed in stable transfectants of hela cells.	stable transfectants of hela cells were isolated which expressed either the full-length 540-amino-acid sindbis virus (sv) nonstructural protein, nsp1 (the form encoded by the mutant, sv(lm21)), or one of four forms with a carboxyl-terminal deletion. sv(lm21), in contrast to standard sv (sv(std)), can replicate in hela cells maintained in low-methionine (lm) medium. expression of full-length nsp1(1-540), nsp1(1-492), or nsp1(1-448) resulted in complementation of sv(std) when infected hela cells w ...	1997	9018135
chimeric sindbis viruses dependent on the ns3 protease of hepatitis c virus.	the hepatitis c virus (hcv) ns3 protease cleaves the viral polyprotein at specific sites to release the putative components of the hcv replication machinery. selective inhibition of this enzyme is predicted to block virus replication, and ns3 is thus considered an attractive candidate for development of anti-hcv therapeutics. to set up a system for analysis of ns3 protease activity in cultured cells, we constructed a family of chimeric sindbis viruses which carry sequences coding for ns3 and its ...	1997	8995667
efficient removal of viruses by a novel polyvinylidene fluoride membrane filter.	virus removal by a novel filter (ultipor vf dv50), comprising three layers of pvdf membrane, has been evaluated by infectivity studies using a range of viruses and conditions. the filter was able to remove at least 6 log of various viruses, i.e. sindbis and semliki forest (40-70 nm), herpes simplex (120-200 nm) and vaccinia (200 x 350 nm), from cell-culture medium or phosphate buffered saline ph 6.8 containing 0.5% albumin. however, the removal of polio virus (25-30 nm) under these conditions wa ...	1997	9128859
role of glycoprotein pe2 in formation and maturation of the sindbis virus spike.	sindbis virus envelope assembly is a multistep process resulting in the maturation of a rigid, highly ordered t=4 icosahedral protein lattice containing 80 spikes composed of trimers of e1-e2 heterodimers. intramolecular disulfide bonds within e1 stabilize e1-e1 associations required for envelope formation and maintenance of the envelope's structural integrity. the structural integrity of the envelope protein lattice is resistant to reduction by dithiothreitol (dtt), indicating that e1 disulfide ...	1997	8995682
sindbis virus infection of neonatal mice results in a severe stress response.	neonatal mice were infected with virus derived from a molecular clone of a laboratory strain of sindbis virus, trsb. the resulting acute fatal infection was typified by few if any of the classic hallmarks of encephalitis, very high levels of interferon-alpha/beta (ifnalphabeta), and lesions in the thymus and hematopoietic tissues usually associated with a severe stress response. infection with an attenuated mutant of trsb, which harbors a single amino acid change in the e2 surface glycoprotein ( ...	1997	9007079
packaging signals in alphaviruses.	alphaviruses synthesize large amounts of both genomic and subgenomic rna in infected cells, but usually only the genomic rna is packaged. this implies the existence of an encapsidation or packaging signal which would be responsible for selectivity. previously, we had identified a region of the sindbis virus genome that interacts specifically with the viral capsid protein. this 132-nucleotide (nt) fragment lies within the coding region of the nsp1 gene (nt 945 to 1076). we proposed that the 132-m ...	1997	8985344
efficient multiplication of a semliki forest virus chimera containing sindbis virus spikes.	using the semliki forest virus (sfv) and sindbis virus (sin) cdnas we have constructed recombinants in which the spike genes were exchanged. analyses of expression showed that the sfv/sin(spike) rna directed efficient assembly of infectious virus, whereas the reciprocal sin/sfv(spike) rna was completely unable to assemble virus. this was apparently due to a defective capsid-spike interaction.	1997	8985423
identification of mutations in a sindbis virus variant able to establish persistent infection in bhk cells: the importance of a mutation in the nsp2 gene.	sindbis virus is a positive strand rna virus that has provided a valuable model for studying virus structure and replication. it is also being developed as a vector for the expression of heterologous proteins. many studies with this virus are carried out in cultured bhk cells where infection is usually highly cytopathic and within 1 or 2 days after infection all of the cells are dead. weiss et al. had established a persistently infected culture of bhk cells by infecting the cells with a virus pr ...	1997	9024811
short-order sindbis vector targeting.		1997	9255777
regulation of brain-derived t cells during acute central nervous system inflammation.	the unique immunologic environment of the central nervous system (cns) regulates most local inflammatory responses. in some circumstances, however, immune-mediated injury to the brain can occur. to understand how lymphocytes are regulated within the cns during an inflammatory response that does not produce immunopathology, we have studied t cells isolated from the brains of mice with sindbis virus (sv) encephalitis. even though they express activation markers, these t cells are arrested in the c ...	1997	9036980
rotation function calculations with glrf program.		1997	9048382
genetic determinants of sindbis virus neuroinvasiveness.	after peripheral inoculation of mice, sindbis virus replicates in a variety of tissues, leading to viremia. in some cases, the virus can enter the central nervous system (cns) and cause lethal encephalitis. the outcome of infection is age and virus strain dependent. recently, two pairs of sindbis virus variants differing in neurovirulence and neuroinvasiveness were derived by limited serial passaging in mouse brain. two early passage isolates (sva and svb) were neurotropic but did not cause leth ...	1997	9060616