Publications

a defective interference-like phenomenon of human hepatitis b virus in chronic carriers.	defective interfering (di) particles have been found in many rna and dna viruses of bacteria, plants, and animals since their first discovery in influenza virus. however, this fundamental phenomenon has not been demonstrated in human natural infections. using a new approach, here we provide the first experimental evidence for the existence of di-like viruses in human chronic carriers of hepatitis b virus (hbv). functional characterization of naturally occurring core internal deletion (cid) varia ...	1998	9420261
effects of defined mutations in the 5' nontranslated region of rubella virus genomic rna on virus viability and macromolecule synthesis.	the 5' end of the genomic rna of rubella virus (rub) contains a 14-nucleotide (nt) single-stranded leader (ss-leader) followed by a stem-and-loop structure [5'(+)sl] (nt 15 to 65), the complement of which at the 3' end of the minus-strand rna [3'(-)sl] has been proposed to function as a promoter for synthesis of genomic plus strands. a second intriguing feature of the 5' end of the rub genomic rna is the presence of a short (17 codons) open reading frame (orf) located between nt 3 and 54; the or ...	1998	9420269
apoptosis in the mouse central nervous system in response to infection with mouse-neurovirulent dengue viruses.	apoptosis has been suggested as a mechanism by which dengue (den) virus infection may cause neuronal cell death (p. desprès, m. flamand, p.-e. ceccaldi, and v. deubel, j. virol. 70:4090-4096, 1996). in this study, we investigated whether apoptotic cell death occurred in the central nervous system (cns) of neonatal mice inoculated intracerebrally with den virus. we showed that serial passage of a wild-type human isolate of den virus in mouse brains selected highly neurovirulent variants which rep ...	1998	9420294
identification of the leader-body junctions for the viral subgenomic mrnas and organization of the simian hemorrhagic fever virus genome: evidence for gene duplication during arterivirus evolution.	simian hemorrhagic fever virus (shfv) was recently reclassified and assigned to the new virus family arteriviridae. during replication, arteriviruses produce a 3' coterminal, nested set of subgenomic mrnas (sgrnas). these sgrnas arise by discontinuous transcription, and each contains a 5' leader sequence which is joined to the body of the mrna through a conserved junction sequence. only the 5'-most open reading frame (orf) is believed to be transcribed from each sgrna. the shfv genome encodes ni ...	1998	9420301
a single point mutation controls the cholesterol dependence of semliki forest virus entry and exit.	membrane fusion and budding are key steps in the life cycle of all enveloped viruses. semliki forest virus (sfv) is an enveloped alphavirus that requires cellular membrane cholesterol for both membrane fusion and efficient exit of progeny virus from infected cells. we selected an sfv mutant, srf-3, that was strikingly independent of cholesterol for growth. this phenotype was conferred by a single amino acid change in the e1 spike protein subunit, proline 226 to serine, that increased the cholest ...	1998	9425157
development of a chimeric sindbis virus with enhanced per os infection of aedes aegypti.	the te/3'2j double subgenomic sindbis (dssin) viruses have been used to stably express genes in aedes aegypti nerve and salivary gland tissues. however, because these viruses inefficiently infect ae. aegypti when administered by the per os route, te/3'2j viruses must be intrathoracically inoculated into the mosquitoes to infect these tissues. a malaysian sindbis (sin) virus isolate (mre16) does efficiently infect ae. aegypti midgut tissues after ingestion, and approximately 95% of these mosquito ...	1998	9527919
noncytopathic sindbis virus rna vectors for heterologous gene expression.	infection of vertebrate cells with alphaviruses normally leads to prodigious expression of virus-encoded genes and a dramatic inhibition of host protein synthesis. recombinant sindbis viruses and replicons have been useful as vectors for high level foreign gene expression, but the cytopathic effects of viral replication have limited their use to transient studies. we recently selected sindbis replicons capable of persistent, noncytopathic growth in bhk cells and describe here a new generation of ...	1998	9789028
identification and characterization of the escherichia coli-expressed rna-dependent rna polymerase of bamboo mosaic virus.	bamboo mosaic virus (bamv), a member of the potexvirus group, infects primarily members of the bambusoideae. the open reading frame 1 (orf1) of bamv encodes a 155-kda polypeptide that was postulated to be involved in the replication and the formation of cap structure at the 5' end of the viral genome. to characterize the activities associated with the 155-kda viral protein, it was expressed in escherichia coli bl21(de3) cells with thioredoxin, hexahistidine, and s. tag fused consecutively at its ...	1998	9811749
broad-spectrum antiviral activity and mechanism of antiviral action of the fluoroquinolone derivative k-12.	the fluoroquinolone derivatives have been shown to inhibit human immunodeficiency virus (hiv) replication at the transcriptional level. we confirmed the anti-hiv activity of the most potent congener, 8-difluoromethoxy-1-ethyl-6-fluoro-1,4-dihydro-7-[4-(2- methoxyphenyl)-1-piperazinyl]-4-quinolone-3-carboxylic acid (k-12), in both acutely and chronically infected cells. k-12 was active against different strains of hiv-1 (including azt- and ritonavir-resistant hiv-1 strains), hiv-2 and simian immu ...	1998	9875393
alphavirus replicase protein nsp1 induces filopodia and rearrangement of actin filaments.	expression of the nsp1 protein of semliki forest virus and sindbis virus in cultured cells induced filopodia-like extensions containing nsp1 but not f actin. the actin stress fibers disappeared, whereas vimentin, keratin, and tubulin networks remained intact. the effects of nsp1 were dependent on its palmitoylation but not on its enzymatic activities and were also observed in virus-infected cells.	1998	9811773
pogosta disease: clinical observations during an outbreak in the province of north karelia, finland.	to characterize the clinical picture of pogosta disease.	1998	9851265
capping and methylation of mrna by purified recombinant vp4 protein of bluetongue virus.	the core of bluetongue virus (btv) is a multienzyme complex composed of two major proteins (vp7 and vp3) and three minor proteins (vp1, vp4, and vp6) in addition to the viral genome. the core is transcriptionally active and produces capped mrna from which all btv proteins are translated, but the relative role of each core component in the overall reaction process remains unclear. previously we showed that the 76-kda vp4 protein possesses guanylyltransferase activity, a necessary part of the rna ...	1998	9811835
cytoplasmic domain of sendai virus hn protein contains a specific sequence required for its incorporation into virions.	in the assembly of paramyxoviruses, interactions between viral proteins are presumed to be specific. the focus of this study is to elucidate the protein-protein interactions during the final stage of viral assembly that result in the incorporation of the viral envelope proteins into virions. to this end, we examined the specificity of hn incorporation into progeny virions by transiently transfecting hn cdna genes into sendai virus (sv)-infected cells. sv hn expressed from cdna was efficiently in ...	1998	9811709
formation and amplification of a novel tombusvirus defective rna which lacks the 5' nontranslated region of the viral genome.	defective interfering (di) rnas of tomato bushy stunt virus (tbsv) are small, subgenomic, helper-dependent replicons that are believed to be generated primarily by aberrant events during replication of the plus-sense rna genome. prototypical tbsv di rnas contain four noncontiguous segments (regions i through iv) derived from the 5' nontranslated region (ntr) (i), an internal section (ii), and the 3'-terminal portion (iii and iv) of the viral genome. we have studied the formation of these molecul ...	1998	9811726
nuclear import and the evolution of a multifunctional rna-binding protein.	la (ss-b) is a highly expressed protein that is able to bind 3'-oligouridylate and other common rna sequence/structural motifs. by virtue of these interactions, la is present in a myriad of nuclear and cytoplasmic ribonucleoprotein complexes in vivo where it may function as an rna-folding protein or rna chaperone. we have recently characterized the nuclear import pathway of the s. cerevisiae la, lhp1p. the soluble transport factor, or karyopherin, that mediates the import of lhp1p is kap108p/sxm ...	1998	9817748
characterization of diverse viral vector preparations, using a simple and rapid whole-virion dot-blot method.	a number of different viruses have been adapted as gene transfer vectors, including retroviruses, adenoviruses, adenoassociated viruses (aavs), herpes simplex virus, sv40 viruses, and alphaviruses (both semliki forest and sindbis viruses). one of the major rate-limiting and time-consuming steps in the characterization of these vectors is the process of determining the viral vector titers. in addition, there is no "universal" method that can be used to rapidly estimate the titer and the utility o ...	1998	9829539
distinct biology of kaposi's sarcoma-associated herpesvirus from primary lesions and body cavity lymphomas.	the dna sequence for kaposi's sarcoma-associated herpesvirus was originally detected in kaposi's sarcoma biopsy specimens. since its discovery, it has been possible to detect virus in cell lines established from aids-associated body cavity-based b-cell lymphoma and to propagate virus from primary kaposi's sarcoma lesions in a human renal embryonic cell line, 293. in this study, we analyzed the infectivity of kaposi's sarcoma-associated herpesvirus produced from these two sources. viral isolates ...	1998	9811747
overexpression of chicken interferon regulatory factor-1 (ch-irf-1) induces constitutive expression of mhc class i antigens but does not confer virus resistance to a permanent chicken fibroblast cell line.	the chicken fibroblast cell line c32 has been transfected with the chicken homolog (ch-irf-1) of the mammalian transcription factor irf-1. stable transfectants were generated, constitutively overexpressing ch-irf-1 mrna and protein. cells overexpressing ch-irf-1 showed enhanced constitutive expression of mhc class i (b-f, beta-microglobulin) antigens. with increasing number of passages cells with normal b-f iv surface antigen expression accumulated. in the revertants, the amount of ch-irf-1 mrna ...	1998	9831662
a neuron-specific gene transfer by a recombinant defective sindbis virus.	we examined the possibility that sindbis virus, an alpha virus with a single-stranded rna genome, would be applied for neuronal gene transfer. the recombinant defective sindbis viruses were constructed by replacing the structural genes of sindbis virus with genes encoding beta-galactosidase (rdsind-lacz) or enhanced green fluorescent protein (rdsind-egfp). in neuron-glia cocultures prepared from the neocortex, hippocampus, and striatum, egfp or beta-galactosidase was expressed selectively in neu ...	1998	9838041
virus maturation by budding.	enveloped viruses mature by budding at cellular membranes. it has been generally thought that this process is driven by interactions between the viral transmembrane proteins and the internal virion components (core, capsid, or nucleocapsid). this model was particularly applicable to alphaviruses, which require both spike proteins and a nucleocapsid for budding. however, genetic studies have clearly shown that the retrovirus core protein, i.e., the gag protein, is able to form enveloped particles ...	1998	9841669
the alphavirus 3'-nontranslated region: size heterogeneity and arrangement of repeated sequence elements.	the 3'-nontranslated region (ntr) of representative strains of all known alphavirus species was amplified by reverse transcription-polymerase chain reaction. for 23 of them, the 3'-ntr sequence was determined. together with previously published data, this allowed an analysis of the 3'-ntr of the viruses in the genus alphavirus. the length of the 3'-ntrs varied from 77 nt for pixuna virus to 609 nt for bebaru virus. the 19-nt conserved sequence element directly adjacent to the poly(a) tract was f ...	1998	9448694
a novel sialic acid binding site on factor h mediates serum resistance of sialylated neisseria gonorrhoeae.	factor h (fh), a key alternative complement pathway regulator, is a cofactor for factor i-mediated cleavage of c3b. fh consists of 20 short consensus repeat (scr) domains. sialic acid binding domains have previously been localized to fh scrs 6-10 and 13. to examine fh binding on a sialylated microbial surface, we grew neisseria gonorrhoeae in the presence of 5'-cytidinemonophospho-n-acetylneuraminic acid, which sialylates lipooligosaccharide and converts to serum resistance gonococci previously ...	1998	9480984
alphaviruses induce apoptosis in bcl-2-overexpressing cells: evidence for a caspase-mediated, proteolytic inactivation of bcl-2.	bcl-2 oncogene expression plays a role in the establishment of persistent viral infection by blocking virus-induced apoptosis. this might be achieved by preventing virus-induced activation of caspase-3, an il-1beta-converting enzyme (ice)-like cysteine protease that has been implicated in the death effector phase of apoptosis. contrary to this model, we show that three cell types highly overexpressing functional bcl-2 displayed caspase-3 activation and underwent apoptosis in response to infectio ...	1998	9482724
identification and genetic analysis of panama-genotype venezuelan equine encephalitis virus subtype id in peru.	venezuelan equine encephalitis (vee) virus was isolated in 1993, 1994, and 1995 from human cases of acute, undifferentiated, febrile illness in the peruvian amazon basin. two virus isolates were recovered in 1994 from peruvian soldiers at a jungle outpost near pantoja in northern peru, and 10 isolates were obtained from military personnel and civilians in 1993-1995 in iquitos, an urban center in northeastern peru. the genetic relationship of these isolates to other vee virus strains was determin ...	1998	9452290
the rubella virus nonstructural protease requires divalent cations for activity and functions in trans.	the rubella virus (rub) nonstructural (ns) protease is a papain-like cysteine protease (pcp) located in the ns-protein open reading frame (nsp-orf) that cleaves the nsp-orf translation product at a single site to produce two products, p150 (the n-terminal product) and p90 (the c-terminal product). the rub ns protease was found not to function following translation in vitro in a standard rabbit reticulocyte lysate system, although all of the other viral pcps do so. however, in the presence of div ...	1998	9557742
[regulation of expression of human fibroblast interferon gene by human leukocyte interferon and cytopathogenic alpha-virus].		1998	9559136
comparison of sindbis virus-induced pathology in mosquito and vertebrate cell cultures.	we have compared sindbis virus-induced cytopathology in vertebrate and mosquito (aedes albopictus) cell cultures. it has been shown that vertebrate cells undergo apoptosis when infected by sindbis virus and this was confirmed here using hamster cells (bhk). the occurrence of cell death in sindbis virus-infected a. albopictus cells is a cell clone-specific phenomenon and, unlike in bhk cell cultures, mosquito cell death does not correlate with a large induction of apoptosis, as determined by assa ...	1998	9454692
neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented aids patients.	human immunodeficiency virus type 1 (hiv-1) infection of the brain results in viral replication primarily in macrophages and microglia. despite frequent detection of viral genome and proteins in the brains of aids patients with and without hiv dementia, only 20% of aids patients become demented. to investigate the role of viral envelope gene variation in the occurrence of dementia, we examined regions of variability in the viral envelope gene isolated from brains of aids patients. brain-derived ...	1998	9765449
inhibition of nf-kappab activation in combination with bcl-2 expression allows for persistence of first-generation adenovirus vectors in the mouse liver.	nf-kappab is a key regulator of the innate antiviral immune response, due in part to its transcriptional activation of cytokines and adhesion molecules, which, in turn, function in chemotaxis and activation of inflammatory cells. we reported earlier that viral gene expression in hepatocytes transduced with first-generation (e1-deleted) adenoviruses induced nf-kappab activation, elevation of serum cytokines, and hepatocellular apoptosis during the first days postinfusion. these events did not occ ...	1998	9765474
characterization of la crosse virus rna in autopsied central nervous system tissues.	a reverse transcription-pcr (rt-pcr) technique was used to detect la crosse (lac) virus rna in the central nervous system (cns) tissues of two patients who died of lac encephalitis in 1960 and 1978. viral rna was readily detected by rt-pcr although the tissues had been stored frozen for up to 37 years. lac virus was detected in the cerebral cortex but not in other cns tissues. rt-pcr allowed detection of replicative forms of the virus, indicating that the virus was actively replicating in the sp ...	1998	9774588
probing the potential glycoprotein binding site of sindbis virus capsid protein with dioxane and model building.	alphavirus budding from the plasma membrane is initiated by the specific interaction of the nucleocapsid with the cytoplasmic domain of the glycoprotein e2. it was proposed (lee et al., structure 4:531-541, 1996) that binding of the capsid protein residues 108 to 110 (the "n-terminal arm" residues) to a hydrophobic pocket on the surface of the neighboring capsid protein in the crystal structure mimics the binding of the e2 c-terminal residues into this pocket. in addition, structural comparisons ...	1998	9779796
human immunodeficiency virus induces a dual regulation of bcl-2, resulting in persistent infection of cd4(+) t- or monocytic cell lines.	this work aims at characterizing the interplay between human immunodeficiency virus type 1 (hiv-1) and the antiapoptotic cellular protein bcl-2 responsible for a persistent infection in lymphoblastoid t (j.jhan) or monocytic (u937) cells. we report that the kinetics of bcl-2 protein level during the establishment of a chronic infection is biphasic, characterized by a transient decrease followed by restoration to the initial level. the extent and duration of this transient decrease were inversely ...	1998	9811703
viral glycoproteins accumulate in newly formed annulate lamellae following infection of lymphoid cells by human herpesvirus 6.	ultrastructural analysis of hsb-2 t-lymphoid cells and human cord blood mononuclear cells infected with human herpesvirus 6 revealed the presence, in the cell cytoplasm, of annulate lamellae (al), which were absent in uninfected cells. time course analysis of the appearance of al following viral infection showed that no al were visible within the first 72 h postinfection and that their formation correlated with the expression of the late viral glycoprotein gp116. the requirement of active viral ...	1998	9811708
antiapoptotic but not antiviral function of human bcl-2 assists establishment of japanese encephalitis virus persistence in cultured cells.	upon infection of japanese encephalitis virus (jev), baby hamster kidney (bhk-21) and chinese hamster ovary (cho) cells were killed by a mechanism involved in apoptosis. while readily established in a variety of cell lines, jev persistence has never been successfully instituted in bhk-21 and cho cells. since stable expression of human bcl-2 in bhk-21 cells has been shown to delay jev-induced apoptosis, in this study we investigated whether jev persistence could be established in such cells. when ...	1998	9811720
recombinant herpes simplex virus type 1 engineered for targeted binding to erythropoietin receptor-bearing cells.	the utility of recombinant herpes simplex virus type 1 (hsv-1) vectors may be expanded by manipulation of the virus envelope to achieve cell-specific gene delivery. to this end, an hsv-1 mutant virus deleted for glycoprotein c (gc) and the heparan sulfate binding domain of gb (kgbpk-gc-) was engineered to encode different chimeric proteins composed of n-terminally truncated forms of gc and the full-length erythropoietin hormone (epo). biochemical analyses demonstrated that one gc-epo chimeric mo ...	1998	9811702
a review of alphavirus replication in neurons.	alphaviruses are important causes of mosquito-borne viral encephalitis. the prototype alphavirus, sindbis virus, causes encephalomyelitis in mice. the primary target cell for nervous system infection is the neuron. thus, sindbis virus infection of mice provides a model system for studying virus-neuron interactions. the outcome of infection is dependent on the maturity of the targeted neurons and on the strain of sindbis virus used for infection. most sindbis virus strains can induce programmed c ...	1998	9809307
cell-specific transfection of choriocarcinoma cells by using sindbis virus hcg expressing chimeric vector.	the development of sindbis virus vectors that can target specific cell types would provide an important gene therapy strategy. we explored the possibility of designing a sindbis virus vector that can target human choriocarcinoma cells via ligand-receptor interaction. the sindbis virus envelope gene was modified by insertion of the alpha- and beta-hcg genes. the chimeric helper rna was then transfected into bhk cells along with a virus-based expression vector, allowing the production of virus par ...	1998	9675133
viral inactivation of human bone tissue using supercritical fluid extraction.	a new bone tissue process using supercritical carbon dioxide fluid extraction (sfe) has been evaluated for its ability to inactivate or eliminate viruses. four viruses, human immunodeficiency virus type 1 (hiv-1), sindbis virus, polio sabin type i virus, and pseudorabies virus (prv), were exposed to four different processing steps. in addition to supercritical co2, hydrogen peroxide, sodium hydroxide, and ethanol treatments were evaluated. the mean cumulated reduction factors (log10) for the fou ...	1998	9682954
characterization of a baculovirus-encoded rna 5'-triphosphatase.	autographa californica nuclear polyhedrosis virus (acnpv) encodes a 168-amino-acid polypeptide that contains the signature motif of the superfamily of protein phosphatases that act via a covalent cysteinyl phosphate intermediate. the sequence of the acnpv phosphatase is similar to that of the rna triphosphatase domain of the metazoan cellular mrna capping enzyme. here, we show that the purified recombinant acnpv protein is an rna 5'-triphosphatase that hydrolyzes the gamma-phosphate of triphosph ...	1998	9696798
the clathrin endocytic pathway in viral infection.	how important is the clathrin-dependent endocytic pathway for entry of viruses into host cells? while it is widely accepted that semliki forest virus (sfv), an enveloped virus, requires this pathway there are conflicting data concerning the closely related sindbis virus, as well as varying results with picornaviruses such as human rhinovirus 14 (hrv 14) and poliovirus. we have examined the entry mode of sfv, sindbis virus, hrv 14 and poliovirus using a method that identifies single infected cell ...	1998	9707418
elevated extracellular calcium can prevent apoptosis via the calcium-sensing receptor.	the calcium-sensing receptor (car) is a membrane-bound, g-protein-coupled receptor present on parathyroid cells which monitors the level of extracellular calcium (ca2+o) and transduces signals involved in serum calcium regulation. expression of car protein in tissues with functions unrelated to systemic calcium homeostasis, including the brain, suggests that extracellular calcium (ca2+o) may act as a first messenger to regulate diverse cellular functions. to test this hypothesis, we examined the ...	1998	9712695
interactions between the structural domains of the rna replication proteins of plant-infecting rna viruses.	brome mosaic virus (bmv), a positive-strand rna virus, encodes two replication proteins: the 2a protein, which contains polymerase-like sequences, and the 1a protein, with n-terminal putative capping and c-terminal helicase-like sequences. these two proteins are part of a multisubunit complex which is necessary for viral rna replication. we have previously shown that the yeast two-hybrid assay consistently duplicated results obtained from in vivo rna replication assays and biochemical assays of ...	1998	9696810
inducible nitric oxide synthase and nitrotyrosine are found in monocytes/macrophages and/or astrocytes in acute, but not in chronic, multiple sclerosis.	we have examined the localization of inducible nitric oxide synthase (inos) and nitrotyrosine (the product of nitration of tyrosine by peroxynitrite, a highly reactive derivative of nitric oxide [no]) in demyelinating lesions from (i) two young adult patients with acute multiple sclerosis (ms), (ii) a child with ms (consistent with diffuse sclerosis), and (iii) five adult patients with chronic ms. previous reports have suggested a possible correlation between inos, peroxynitrite, related nitroge ...	1998	9665945
binding of sindbis virus to cell surface heparan sulfate.	alphaviruses are arthropod-borne viruses with wide species ranges and diverse tissue tropisms. the cell surface receptors which allow infection of so many different species and cell types are still incompletely characterized. we show here that the widely expressed glycosaminoglycan heparan sulfate can participate in the binding of sindbis virus to cells. enzymatic removal of heparan sulfate or the use of heparan sulfate-deficient cells led to a large reduction in virus binding. sindbis virus bou ...	1998	9696831
adaptation of sindbis virus to bhk cells selects for use of heparan sulfate as an attachment receptor.	attachment of sindbis virus to the cell surface glycosaminoglycan heparan sulfate (hs) and the selection of this phenotype by cell culture adaptation were investigated. virus (tr339) was derived from a cdna clone representing the consensus sequence of strain ar339 (k. l. mcknight, d. a. simpson, s. c. lin, t. a. knott, j. m. polo, d. f. pence, d. b. johannsen, h. w. heidner, n. l. davis, and r. e. johnston, j. virol. 70:1981-1989, 1996) and from mutant clones containing either one or two dominan ...	1998	9696832
identification of specific nucleotide sequences within the conserved 3'-sl in the dengue type 2 virus genome required for replication.	the flavivirus genome is a positive-stranded approximately 11-kb rna including 5' and 3' noncoding regions (ncr) of approximately 100 and 400 to 600 nucleotides (nt), respectively. the 3' ncr contains adjacent, thermodynamically stable, conserved short and long stem-and-loop structures (the 3'-sl), formed by the 3'-terminal approximately 100 nt. the nucleotide sequences within the 3'-sl are not well conserved among species. we examined the requirement for the 3'-sl in the context of dengue virus ...	1998	9696848
a novel method of cell-specific mrna transfection.	in this study, we developed a cell-specific mrna transfection system using streptavidin-protein a (st-pa) fusion protein and monoclonal antibodies (mabs). we previously reported that st-pa fusion protein and mab complexes can transfer certain biotinylated proteins into specific cell types. at this time, we combined an in vitro transcribed biotinylated and self-replicating sindbis virus genomic rna with st-pa fusion protein and mabs. in the presence of cationic liposomes, to prevent rna degradati ...	1998	9682217
the role of low ph and disulfide shuffling in the entry and fusion of semliki forest virus and sindbis virus.	semliki forest virus (sfv), an enveloped alphavirus, infects cells via a membrane fusion reaction that is induced by the low ph in endocytic vesicles. the role of low ph in the entry of the alphavirus sindbis virus (sin) is unclear, and an alternative fusion mechanism involving receptor-induced disulfide bond rearrangements at neutral ph has been proposed. the entry properties of sfv and sin were here compared in parallel using treatment with the weak base nh4cl or the vacuolar atpase inhibitors ...	1998	9721245
cleavage of highly structured viral rna molecules by combinatorial libraries of hairpin ribozymes. the most effective ribozymes are not predicted by substrate selection rules.	combinatorial libraries of hairpin ribozymes representing all possible cleavage specificities (>10(5)) were used to evaluate all ribozyme cleavage sites within a large (4.2-kilobase) and highly structured viral mrna, the 26 s subgenomic rna of sindbis virus. the combinatorial approach simultaneously accounts for target site structure and dynamics, together with ribozyme folding, and the sequences that result in a ribozyme-substrate complex with maximal activity. primer extension was used to map ...	1998	9722591
use of the sindbis replicon system for expression of lacrosse virus envelope proteins in mosquito cells.	the sindbis replicon expression system was used to express la crosse (lac) virus envelope glycoprotein genes in both mammalian and mosquito cell culture. replicon expressed lac proteins had correct molecular mass (mr) and were antigenically similar to wild type lac envelope proteins. in addition, lac g1 and g2 proteins colocalized when expressed from separate constructs in both mammalian and mosquito cells suggesting that they were trafficked through the cell similarly to wild type lac proteins. ...	1998	9722880
analysis of constructed e gene mutants of mouse hepatitis virus confirms a pivotal role for e protein in coronavirus assembly.	expression studies have shown that the coronavirus small envelope protein e and the much more abundant membrane glycoprotein m are both necessary and sufficient for the assembly of virus-like particles in cells. as a step toward understanding the function of the mouse hepatitis virus (mhv) e protein, we carried out clustered charged-to-alanine mutagenesis on the e gene and incorporated the resulting mutations into the mhv genome by targeted recombination. of the four possible clustered charged-t ...	1998	9733825
comparison of the neurovirulence of a vaccine and a wild-type mumps virus strain in the developing rat brain.	prior to the adoption of widespread vaccination programs, mumps virus was the leading cause of virus-induced central nervous system (cns) disease. mumps virus-associated cns complications in vaccinees continue to be reported; outside the united states, some of these complications have been attributed to vaccination with insufficiently attenuated neurovirulent vaccine strains. the development of potentially neurovirulent, live, attenuated mumps virus vaccines stems largely from the lack of an ani ...	1998	9733843
the susceptibility of mice to immune-mediated neurologic disease correlates with the degree to which their lymphocytes resist the effects of brain-derived gangliosides.	sjl mice develop immune-mediated disorders of the central nervous system (cns) when infected with certain neurotropic viruses or when immunized with myelin ags. other strains including balb/c are more resistant to these diseases. during sindbis virus-induced encephalitis, both mice are easily infected and elicit rapid mononuclear cell inflammation in the brain. however, only sjl mice develop immune-mediated paralysis; balb/c mice remain asymptomatic. to understand how the same stimulus produces ...	1998	9743332
fractalkine and cx3cr1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow.	leukocyte migration into sites of inflammation involves multiple molecular interactions between leukocytes and vascular endothelial cells, mediating sequential leukocyte capture, rolling, and firm adhesion. in this study, we tested the role of molecular interactions between fractalkine (fkn), a transmembrane mucin-chemokine hybrid molecule expressed on activated endothelium, and its receptor (cx3cr1) in leukocyte capture, firm adhesion, and activation under physiologic flow conditions. immobiliz ...	1998	9782118
human biliary glycoproteins function as receptors for interspecies transfer of mouse hepatitis virus.	a variant mouse hepatitis virus (mhv), designated mhv-h2, was isolated by serial passage in mixed cultures of permissive dbt cells and nonpermissive syrian hamster kidney (bhk) cells. mhv-h2 replicated efficiently in hamster, mouse, primate kidney (vero, cos 1, cos 7), and human adenocarcinoma (hrt) cell lines but failed to replicate in porcine testicular (st), feline kidney (crfk), and canine kidney (mdck) cells. to understand the molecular basis for coronavirus cross-species transfer into huma ...	1998	9782263
effect of clostridium difficile toxin a on human colonic lamina propria cells: early loss of macrophages followed by t-cell apoptosis.	we have previously shown that clostridium difficile toxin a induces detachment of human colonic epithelial cells from the basement membrane and subsequent cell death by apoptosis. because these cells require adhesion-dependent signalling from the extracellular matrix for survival, their detachment from the basement membrane by other means also induces apoptosis. the role of toxin a in the induction of apoptosis therefore remains to be determined. in addition, sensitivities to c. difficile toxin ...	1998	9784558
measles virus fusion protein is palmitoylated on transmembrane-intracytoplasmic cysteine residues which participate in cell fusion.	[3h]palmitic acid was metabolically incorporated into the viral fusion protein (f) of edmonston or freshly isolated measles virus (mv) during infection of human lymphoid or vero cells. the uncleaved precursor f0 and the f1 subunit from infected cells and extracellular virus were both labeled, indicating that palmitoylation can take place prior to f0 cleavage and that palmitoylated f protein was incorporated into virus particles. [3h]palmitic acid was released from f protein upon hydroxylamine or ...	1998	9733862
detection and quantitation of human respiratory syncytial virus (rsv) using minigenome cdna and a sindbis virus replicon: a prototype assay for negative-strand rna viruses.	we describe here a novel approach for detecting and quantitating human respiratory syncytial virus (rsv) based on expression of a reporter gene from an rsv minigenome. bhk cells were cytoplasmically transformed with a noncytopathic sindbis virus replicon expressing t7 rna polymerase. these cells were then cotransfected with t7 expression plasmids that contain the cdna of an rsv minigenome and the genes for rsv nucleocapsid proteins n, p, and l. the minigenome contains a reporter gene such as lac ...	1998	9813215
effects of site-directed mutations of transmembrane cysteines in sindbis virus e1 and e2 glycoproteins on palmitylation and virus replication.	the two glycoproteins that form the external spikes of the alphaviruses are type 1 membrane proteins whose transmembrane domains of hydrophobic amino acids are close to the carboxyl termini of the polypeptides and anchor the proteins in the lipid bilayer. most of the members of the alphavirus genus contain within this transmembrane sequence one or more highly conserved cysteines, which are positioned close to the cytoplasmic face of the lipid bilayer. cysteines in the cytoplasmic domains of the ...	1998	9740777
differential downstream functions of protein kinase ceta and -theta in el4 mouse thymoma cells.	sensitive el4 mouse thymoma cells (s-el4) respond to phorbol esters with growth inhibition, adherence to substrate, and production of cytokines including interleukin 2. since these cells express several of the phorbol ester-sensitive protein kinase c (pkc) isozymes, the function of each isozyme remains unclear. previous studies demonstrated that s-el4 cells expressed substantially more pkceta and pkctheta than did el4 cells resistant to phorbol esters (r-el4). to examine potential roles for pkce ...	1998	9765301
protection against fatal sindbis virus encephalitis by beclin, a novel bcl-2-interacting protein.	bcl-2, the prototypic cellular antiapoptotic gene, decreases sindbis virus replication and sindbis virus-induced apoptosis in mouse brains, resulting in protection against lethal encephalitis. to investigate potential mechanisms by which bcl-2 protects against central nervous system sindbis virus infection, we performed a yeast two-hybrid screen to identify bcl-2-interacting gene products in an adult mouse brain library. we identified a novel 60-kda coiled-coil protein, beclin, which we confirme ...	1998	9765397
ribosomal s27a coding sequences upstream of ubiquitin coding sequences in the genome of a pestivirus.	molecular characterization of cytopathogenic (cp) bovine viral diarrhea virus (bvdv) strain cp rit, a temperature-sensitive strain widely used for vaccination, revealed that the viral genomic rna is about 15.2 kb long, which is about 2.9 kb longer than the one of noncytopathogenic (noncp) bvdv strains. molecular cloning and nucleotide sequencing of parts of the genome resulted in the identification of a duplication of the genomic region encoding nonstructural proteins ns3, ns4a, and part of ns4b ...	1998	9765411
isolation of an arabidopsis thaliana mutant in which the multiplication of both cucumber mosaic virus and turnip crinkle virus is affected.	during the systemic infection of plants by viruses, host factors play an important role in supporting virus multiplication. to identify and characterize the host factors involved in this process, we isolated an arabidopsis thaliana mutant named rb663, in which accumulation of the coat protein (cp) of cucumber mosaic virus (cmv) in upper uninoculated leaves was delayed. genetic analyses suggested that the phenotype of delayed accumulation of cmv cp in rb663 plants was controlled by a monogenic, r ...	1998	9765416
cyclin-dependent kinases participate in death of neurons evoked by dna-damaging agents.	previous reports have indicated that dna-damaging treatments including certain anticancer therapeutics cause death of postmitotic nerve cells both in vitro and in vivo. accordingly, it has become important to understand the signaling events that control this process. we recently hypothesized that certain cell cycle molecules may play an important role in neuronal death signaling evoked by dna damage. consequently, we examined whether cyclin-dependent kinase inhibitors (ckis) and dominant-negativ ...	1998	9786955
dna immunization against herpes simplex virus: enhanced efficacy using a sindbis virus-based vector.	previously we reported the development of a plasmid dna expression vector system derived from sindbis virus (t. w. dubensky, jr., et al., j. virol. 70:508-519, 1996). in vitro, such vectors exhibit high-level heterologous gene expression via self-amplifying cytoplasmic rna replication. in the present study, we demonstrated the in vivo efficacy of the sindbis virus-based psin vectors as dna vaccines. a single intramuscular immunization of balb/c mice with psin vectors expressing the glycoprotein ...	1998	9444987
molecular genetic study of the interaction of sindbis virus e2 with ross river virus e1 for virus budding.	glycoprotein pe2 of sindbis virus will form a heterodimer with glycoprotein e1 of ross river virus that is cleaved to an e2/e1 heterodimer and transported to the cell plasma membrane, but this chimeric heterodimer fails to interact with sindbis virus nucleocapsids, and very little budding to produce mature virus occurs upon infection with chimeric viruses. we have isolated in both sindbis virus e2 and in ross river virus e1 a series of suppressing mutations that adapt these two proteins to one a ...	1998	9445043
structural localization of the e3 glycoprotein in attenuated sindbis virus mutants.	we have determined the three-dimensional structures of the wild-type sindbis virus and two of its mutants that retain the e3 sequence within pe2. using difference imaging between these mutants and the wild-type virus, we have assigned a location for the 64-amino-acid sequence corresponding to e3 in the mutant spike complex. in the wild-type virus, the spike is composed of an e1-e2 heterotrimer. the e3 protein was found to protrude midway between the center of the spike complex and the tips. base ...	1998	9445057
modulation of cell death by bcl-xl through caspase interaction.	the caspases are cysteine proteases that have been implicated in the execution of programmed cell death in organisms ranging from nematodes to humans. many members of the bcl-2 family, including bcl-xl, are potent inhibitors of programmed cell death and inhibit activation of caspases in cells. here, we report a direct interaction between caspases and bcl-xl. the loop domain of bcl-xl is cleaved by caspases in vitro and in cells induced to undergo apoptotic death after sindbis virus infection or ...	1998	9435230
acute infection of sindbis virus induces phosphorylation and intracellular translocation of small heat shock protein hsp27 and activation of p38 map kinase signaling pathway.	in general, viral infection is supposed to induce stress responses in the host cell. however, very few detailed observations about virus-induced stress responses have been reported. here we investigated specific stress responses in vero cells infected with sindbis virus (sv), a single-stranded rna virus, acute infection with which is known to cause apoptotic cell death in the host cells. prior to the onset of apoptosis, p38 mitogen-activated protein kinase (mapk) and c-jun nh2-terminal kinases ( ...	1998	9875220
recombination of nonreplicative rna precursors of sindbis virus in infected cells overexpressing murine-inducible nitric oxide synthase.	the sindbis virus-based sinrep5 expression system is one of the most efficient vectors for gene transfer leading to fast and high expression of the gene of interest. this system was used to transfect vascular endothelial and smooth muscle cells using murine inducible nitric oxide synthase (minos) as a reporter gene. infection of both cell types leads to high expression levels of minos. in addition, the harvested supernatant of these infected cells was used for further rounds of infections, demon ...	1998	9878569
removal of viruses from human intravenous immune globulin by 35 nm nanofiltration.	viral safety is an important prerequisite for clinical immunoglobulin preparations. a common manufacturing practice is to utilize several virus removal/inactivation process steps to ensure the safety of human intravenous immunoglobulin (ivig). in this regard, we examined the use of planova 35 nm filters to reduce potential loads of both non-enveloped and enveloped viruses prior to end-stage solvent detergent treatment. the nanofiltration process was validated for removal of a variety of envelope ...	1998	10403036
inhibition versus induction of apoptosis by proteasome inhibitors depends on concentration.	we previously established that nf-kappab dna binding activity is required for sindbis virus (sv)-induced apoptosis. to investigate whether sv induces nuclear translocation of nf-kappab via the proteasomal degradation pathway, we utilized mg132, a peptide aldehyde inhibitor of the catalytic subunit of the proteasome. 20 microm mg132 completely abrogated sv-induced nf-kappab nuclear activity at early time points after infection. parallel measures of cell viability 48 h after sv infection revealed ...	1998	10200512
rna virus vectors: where are we and where do we need to go?		1998	9788984
protease inhibitors as antiviral agents.	currently, there are a number of approved antiviral agents for use in the treatment of viral infections. however, many instances exist in which the use of a second antiviral agent would be beneficial because it would allow the option of either an alternative or a combination therapeutic approach. accordingly, virus-encoded proteases have emerged as new targets for antiviral intervention. molecular studies have indicated that viral proteases play a critical role in the life cycle of many viruses ...	1998	9767059
directed changes in the number of double-stranded rna genomic segments in bacteriophage phi6.	bacteriophage phi6 has a genome of three segments of double-stranded rna. the segments are designated s, m, and l. each segment has a unique packaging site, pac, near the 5' end of the plus strand. the plus strands of the segments are normally packaged in the order s, m, l. chimeras of segment m and s in which segment m is at the 5' end of the plus strand can be stably incorporated into the virion; however, an independent segment s must be included along with normal segment l, even if it contain ...	1998	9520468
construction of recombinant sindbis-based expression vectors for the study of hcv genes and their products.	there are currently no methods for propogating hepatitis c virus (hcv) in culture useful for the analysis of viral proteins. therefore, we have utilized sindbis virus-based vectors to express and study hcv genes and their products.	1999	21374397
vaccines timeline. interview by philip cohen.		1999	10559053
adding the third dimension to virus life cycles: three-dimensional reconstruction of icosahedral viruses from cryo-electron micrographs.	viruses are cellular parasites. the linkage between viral and host functions makes the study of a viral life cycle an important key to cellular functions. a deeper understanding of many aspects of viral life cycles has emerged from coordinated molecular and structural studies carried out with a wide range of viral pathogens. structural studies of viruses by means of cryo-electron microscopy and three-dimensional image reconstruction methods have grown explosively in the last decade. here we revi ...	1999	10585969
tnfalpha, interferon, and stress response induction as a function of age-related susceptibility to fatal sindbis virus infection of mice.	the age-related acquisition of resistance to fatal sindbis virus infection was examined using a molecularly cloned laboratory strain of the ar339 isolate designated trsb. trsb caused 100% mortality in mice up to 5 days of age. resistance to fatal infection developed abruptly between 5 and 9 days of age. lethal sindbis virus infection of mice inoculated at 4 days of age was characterized by high levels of virus replication, induction of high levels of interferon-alpha/beta and tnf-alpha and sever ...	1999	10544107
identification of functional domains in the 14-kilodalton envelope protein (a27l) of vaccinia virus.	the mechanism of entry of vaccinia virus (vv) into cells is still a poorly understood process. a 14-kda protein (encoded by the a27l gene) in the envelope of intracellular mature virus (imv) has been implicated in virus-cell attachment, virus-cell fusion, and virus release from cells. we have previously described the structural organization of the vv 14-kda protein, consisting of a triple-stranded coiled-coil region responsible for oligomer formation and a predicted leu zipper-like third alpha h ...	1999	10516016
polypyrimidine tract-binding protein binds to the complementary strand of the mouse hepatitis virus 3' untranslated region, thereby altering rna conformation.	mouse hepatitis virus (mhv) rna transcription is regulated mainly by the leader and intergenic (ig) sequences. however, a previous study has shown that the 3' untranslated region (3'-utr) of the viral genome is also required for subgenomic mrna transcription; deletion of nucleotides (nt) 270 to 305 from the 3'-utr completely abolished subgenomic mrna transcription without affecting minus-strand rna synthesis (y.-j. lin, x. zhang, r.-c. wu, and m. m. c. lai, j. virol. 70:7236-7240, 1996), suggest ...	1999	10516017
assignment of the multifunctional ns3 protein of bovine viral diarrhea virus during rna replication: an in vivo and in vitro study.	studies on the replication of the pestivirus bovine viral diarrhea virus (bvdv) were considerably facilitated by the recent discovery of an autonomous subgenomic bvdv rna replicon (di9c). di9c comprises mainly the untranslated regions of the viral genome and the coding region of the nonstructural proteins ns3, ns4a, ns4b, ns5a, and ns5b. to assess the significance of the ns3-associated nucleoside triphosphatase/helicase activity during rna replication and to explore other functional features of ...	1999	10516027
binding of tumour necrosis factor-alpha (tnf-alpha) to tnf-ri induces caspase(s)-dependent apoptosis in human cholangiocarcinoma cell lines.	cholangiocarcinoma (cca), a tumour of the bile duct epithelium, occurs with a higher incidence in south-east asian countries than in europe and north america. the prognosis is poor, due to the unavailability of early diagnosis and the tumours being relatively resistant to chemotherapy. in the present study one of the fatal routes of this tumour was studied. this death was stimulated by tnf-alpha. tnf-alpha at a concentration of 760 pg/ml and 100 pg/ml in the presence of 1 microgram/ml actinomyci ...	1999	10209503
endoprotease pace4 is ca2+-dependent and temperature-sensitive and can partly rescue the phenotype of a furin-deficient cell strain.	pace4 is a member of the eukaryotic subtilisin-like endoprotease family. the expression of human pace4 in rpe.40 cells (furin-null mutants derived from chinese hamster ovary k1 cells) resulted in the rescue of a number of wild-type characteristics, including sensitivity to sindbis virus and the ability to process the low-density-lipoprotein receptor-related protein. expression of pace4 in these cells failed to restore wild-type sensitivity to pseudomonas exotoxin a. co-expression of human pace4 ...	1999	10215603
decreased intracellular superoxide levels activate sindbis virus-induced apoptosis.	infection of many cultured cell types with sindbis virus (sv), an alphavirus, triggers apoptosis through a commonly utilized caspase activation pathway. however, the upstream signals by which sv activates downstream apoptotic effectors, including caspases, remain unclear. here we report that in at-3 prostate carcinoma cells, sv infection decreases superoxide (o-2) levels within minutes of infection as monitored by an aconitase activity assay. this sv-induced decrease in o-2 levels appears to act ...	1999	10224137
human cd46 enhances nitric oxide production in mouse macrophages in response to measles virus infection in the presence of gamma interferon: dependence on the cd46 cytoplasmic domains.	cd46 is a transmembrane complement regulatory protein widely expressed on nucleated human cells. laboratory-adapted strains of measles virus (mv) bind to the extracellular domains of cd46 to enter human cells. the cytoplasmic portion of cd46 consists of a common juxtamembrane region and different distal sequences called cyt1 and cyt2. the biological functions of these cytoplasmic sequences are unknown. in this study, we show that expression of human cd46 with the cyt1 cytoplasmic domain in mouse ...	1999	10233938
characterization of a chinese hamster ovary cell line developed by retroviral insertional mutagenesis that is resistant to sindbis virus infection.	the alphavirus sindbis virus (sv) has a wide host range and infects many types of cultured cells in vitro. the outcome of infection is dependent on the strain of virus used for infection and the properties of the cells infected. to identify cellular determinants of susceptibility to sv infection we mutagenized chinese hamster ovary (cho) cells by retroviral insertion with a vector containing the neomycin resistance gene that allowed selection for integration into transcriptionally active genes. ...	1999	10233953
identification of a linear heparin binding domain for human respiratory syncytial virus attachment glycoprotein g.	respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract disease in infants and young children worldwide. infection is mediated, in part, by an initial interaction between attachment protein (g) and a highly sulfated heparin-like glycosaminoglycan (gag) located on the cell surface. synthetic overlapping peptides derived from consensus sequences of the g protein ectodomain from both rsv subgroups a and b were tested by heparin-agarose affinity chromatography for their abi ...	1999	10400758
oligomerization within virions and subcellular localization of human immunodeficiency virus type 1 integrase.	previous biochemical and genetic evidence indicated that the functional form of retroviral integrase protein (in) is a multimer. a direct demonstration of in oligomerization during the infectious cycle was, however, missing, due to the absence of a sensitive detection method. we describe here the generation of infectious human immunodeficiency virus type 1 (hiv-1) viral clones carrying in protein tagged with highly antigenic epitopes. in this setting, we could readily visualize in both in produc ...	1999	10233971
an epitope of the semliki forest virus fusion protein exposed during virus-membrane fusion.	semliki forest virus (sfv) is an enveloped alphavirus that infects cells via a membrane fusion reaction triggered by acidic ph in the endocytic pathway. fusion is mediated by the spike protein e1 subunit, an integral membrane protein that contains the viral fusion peptide and forms a stable homotrimer during fusion. we have characterized four monoclonal antibodies (mabs) specific for the acid conformation of e1. these mabs did not inhibit fusion, suggesting that they bind to an e1 region differe ...	1999	10559317
putative rna capping activities encoded by brome mosaic virus: methylation and covalent binding of guanylate by replicase protein 1a.	brome mosaic virus (bmv) rna replication is directed by two virus-encoded proteins, 1a and 2a. the amino-terminal half of 1a is a distant homolog of alphavirus nonstructural protein nsp1, which has been implicated in capping viral rnas. in this study, we examined the enzymatic activities of bmv 1a expressed in yeast, where the protein is fully functional in rna replication. 1a methylated gtp, dgtp, and the cap analogs gpppg and gpppa, using s-adenosylmethionine (adomet) as the methyl donor. prod ...	1999	10559320
infecting larval arthropods with a chimeric, double subgenomic sindbis virus vector to express genes of interest.		1999	10572634
ectopic gene expression and homeotic transformations in arthropods using recombinant sindbis viruses.	the morphological diversity of arthropods makes them attractive subjects for studying the evolution of developmental mechanisms. comparative analyses suggest that arthropod diversity has arisen largely as a result of changes in expression patterns of genes that control development. direct analysis of how a particular gene functions in a given species during development is hindered by the lack of broadly applicable techniques for manipulating gene expression.	1999	10574759
dna and rna-based vaccines: principles, progress and prospects.	dna vaccines were introduced less than a decade ago but have already been applied to a wide range of infectious and malignant diseases. here we review the current understanding of the mechanisms underlying the activities of these new vaccines. we focus on recent strategies designed to enhance their function including the use of immunostimulatory (cpg) sequences, dendritic cells (dc), co-stimulatory molecules and cytokine- and chemokine-adjuvants. although genetic vaccines have been significantly ...	1999	10580187
mutagenesis of the rgd motif in the yellow fever virus 17d envelope protein.	the envelope protein of yellow fever virus 17d (yfv-17d) contains a solvent-exposed rgd motif, which has led to the suggestion that integrins may function as cellular receptors for yfv-17d. we found that mutating the rgd motif to rge had no effect on viral titers, whereas changing rgd to tgd, tge, tad, tae, or rgs led to reduced titers. substitution of rgd by rad or rae yielded rna genomes that replicated in mammalian cells but could not spread to neighboring cells at 37 degrees c. these mutants ...	1999	10603320
primary megakaryocytes reveal a role for transcription factor nf-e2 in integrin alpha iib beta 3 signaling.	platelet integrin alphaiibbeta3 responds to intracellular signals by binding fibrinogen and triggering cytoskeletal reorganization, but the mechanisms of alphaiibbeta3 signaling remain poorly understood. to better understand this process, we established conditions to study alphaiibbeta3 signaling in primary murine megakaryocytes. unlike platelets, these platelet precursors are amenable to genetic manipulation. cytokine-stimulated bone marrow cultures produced three arbitrary populations of alpha ...	1999	10613901
an outbreak of west nile fever among migrants in kisangani, democratic republic of congo.	in february 1998, an outbreak of acute febrile illness was reported from the kapalata military camp in kisangani, the democratic republic of congo. the illness was characterized by an acute onset of fever associated with severe headache, arthralgia, backache, neurologic signs, abdominal pain, and coughing. in 1 individual, hemorrhagic manifestations were observed. the neurologic signs included an altered level of consciousness, convulsions, and coma. malaria was initially suspected, but the pati ...	1999	10674664
efficient gene delivery into adult cardiomyocytes by recombinant sindbis virus.	somatic gene therapy as a potential strategy for the treatment of myocardial diseases relies on an efficient gene transfer into cardiac muscle cells. the difficulty of delivering genes into adult cardiomyocytes exists not only in vivo but also in primary culture systems. therefore, possibilities for ex vivo gene transfer and the in vitro study of physiological processes by reverse genetics are limited. we investigated the potential of an alphavirus-based vector system to transduce adult rat card ...	1999	10682322
the inflammatory response to nonfatal sindbis virus infection of the nervous system is more severe in sjl than in balb/c mice and is associated with low levels of il-4 mrna and high levels of il-10-producing cd4+ t cells.	sjl mice are susceptible to inflammatory autoimmune diseases of the central nervous system (cns), while balb/c mice are relatively resistant. to understand differences in immune responses that may contribute to autoimmune neurologic disease, we compared the responses of sjl and balb/c mice to infection with sindbis virus, a virus that causes acute nonfatal encephalomyelitis in both strains of mice. clearance of virus was similar, but sjl mice developed a more intense inflammatory response in the ...	1999	9973422
seroprevalence of dengue, chikungunya and sindbis virus infections in german aid workers.	vector-borne virus infections were studied in 670 german overseas aid workers who had spent an average of 37.7 months in tropical areas of africa and asia. antibodies to dengue viruses (den) were detected by indirect immunofluorescence assay in 43/670 (6.4%) aid workers. of these 43, 41 (95.3%) were also positive for antibodies to dengue by haemagglutination inhibition assay. the highest seroprevalence was in aid workers returning from thailand (19.4%), benin (14.8%) and burkina faso (9.2%). ant ...	1999	10219635