induction of human papillomavirus type 16-specific immunologic responses in a normal and an human papillomavirus-infected populations.human papillomavirus (hpv) infection, especially with the oncogenic genotypes, is the most important risk factor for developing cervical cancer. we focused on generating hpv16 e7-specific cytotoxic cd8(+) t lymphocytes and evaluating hpv16 e7-specific immune responses in hpv16-infected and uninfected populations. peripheral blood mononuclear cells (pbmcs) were first collected from an uninfected group with an human lymphocyte antigen (hla) a2 haplotype (four volunteers). mature monocyte-derived d ...200515819706
gamma interferon-dependent, noncytolytic clearance of sindbis virus infection from neurons in vitro.due to the nonrenewable nature of neurons, recovery from viral infection of the central nervous system requires noncytopathic mechanisms for control of virus replication. recovery from alphavirus encephalitis can occur without apparent neurological damage through the effects of antibody and gamma interferon (ifn-gamma). to establish an in vitro cell culture system that will allow the study of mechanisms of ifn-gamma-mediated control of sindbis virus (sinv) replication in neurons, we have charact ...200515827152
rift valley fever virus nonstructural protein nss promotes viral rna replication and transcription in a minigenome system.rift valley fever virus (rvfv), which belongs to the genus phlebovirus, family bunyaviridae, has a tripartite negative-strand genome (s, m, and l segments) and is an important mosquito-borne pathogen for domestic animals and humans. we established an rvfv t7 rna polymerase-driven minigenome system in which t7 rna polymerase from an expression plasmid drove expression of rna transcripts for viral proteins and minigenome rna transcripts carrying a reporter gene between both termini of the m rna se ...200515827175
ross river virus disease reemergence, fiji, 2003-2004.we report 2 clinically characteristic and serologically positive cases of ross river virus infection in canadian tourists who visited fiji in late 2003 and early 2004. this report suggests that ross river virus is once again circulating in fiji, where it apparently disappeared after causing an epidemic in 1979 to 1980.200515829203
effective protection of pigs against lethal pseudorabies virus infection after a single injection of low-dose sindbis-derived plasmids encoding prv gb, gc and gd glycoproteins.this study compared protection of pigs against lethal pseudorabies virus (prv) infection induced by a single injection of various quantities of sindbis virus-derived plasmids encoding prv glycoproteins gb, gc and gd. pigs were injected with 340, 68 or 13 microg of each plasmid. few immune differences were observed after dna injection and more importantly the pigs of the three groups were equally protected against virulent prv infection. single-shot injection of 13 microg of each prv glycoprotein ...200515837372
bcl-2-related protein a1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury.hyperoxic acute lung injury (hali) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by il-11 and other interventions. we hypothesized that bfl-1/a1, an antiapoptotic bcl-2 protein, is a critical regulator of hali and a mediator of il-11-induced cytoprotection. to test this, we characterized the expression of a1 and the oxygen susceptibility of wt and il-11 tg(+) mice with normal and null a1 loci. in wt mice, 100% o(2) caused tunel(+) cell death, ...200515841185
stereophysicochemical variability plots highlight conserved antigenic areas in flaviviruses.flaviviruses, which include dengue (dv) and west nile (wn), mutate in response to immune system pressure. identifying escape mutants, variant progeny that replicate in the presence of neutralizing antibodies, is a common way to identify functionally important residues of viral proteins. however, the mutations typically occur at variable positions on the viral surface that are not essential for viral replication. methods are needed to determine the true targets of the neutralizing antibodies.200515845145
intranasal vaccination induces protective immunity against intranasal infection with virulent francisella tularensis biovar a.the inhalation of francisella tularensis biovar a causes pneumonic tularemia associated with high morbidity and mortality rates in humans. exposure to f. tularensis usually occurs by accident, but there is increasing awareness that f. tularensis may be deliberately released in an act of bioterrorism or war. the development of a vaccine against pneumonic tularemia has been limited by a lack of information regarding the mechanisms required to protect against this disease. vaccine models for f. tul ...200515845466
virus-inducible reporter genes as a tool for detecting and quantifying influenza a virus replication.the use of influenza a virus-inducible reporter gene segments in detecting influenza a virus replication was investigated. the rna polymerase i promoter/terminator cassette was used to express rna transcripts encoding green fluorescence protein or firefly luciferase flanked by the untranslated regions of the influenza a/wsn/33 nucleoprotein (np) segment. reporter gene activity was detected after reconstitution of the influenza a virus polymerase complex from cdna or after virus infection, and wa ...200515847914
high-level expression of marek's disease virus glycoprotein c is detrimental to virus growth in vitro.expression levels of marek's disease virus (mdv) glycoprotein c (gc) are significantly reduced after serial virus passage in cell culture. reduced gc expression coincides with enhanced mdv growth in vitro and attenuation. to analyze this phenomenon in detail, a full-length infectious mdv clone was modified by red-based and shuttle mutagenesis in escherichia coli. besides a gc-negative deletion mutant harboring a kanamycin resistance gene, a markerless mutant with the u(l)44 gene deleted was cons ...200515857974
roles of cd4+ t-cell-independent and -dependent antibody responses in the control of influenza virus infection: evidence for noncognate cd4+ t-cell activities that enhance the therapeutic activity of antiviral antibodies.previous studies have indicated that b cells make a significant contribution to the resolution of influenza virus infection. to determine how b cells participate in the control of the infection, we transferred intact, major histocompatibility complex class ii (mhc-ii)-negative or b-cell receptor (bcr)-transgenic spleen cells into b-cell-deficient and cd8(+) t-cell-depleted mumt mice, termed mumt(-8), and tested them for ability to recover from infection. mumt(-8) mice that received no spleen cel ...200515857980
targeting human glioblastoma cells: comparison of nine viruses with oncolytic potential.brain tumors classified as glioblastomas have proven refractory to treatment and generally result in death within a year of diagnosis. we used seven in vitro tests and one in vivo trial to compare the efficacy of nine different viruses for targeting human glioblastoma. green fluorescent protein (gfp)-expressing vesicular stomatitis (vsv), sindbis virus, pseudorabies virus (prv), adeno-associated virus (aav), and minute virus of mice i-strain (mvmi) and mvmp all infected glioblastoma cells. mouse ...200515857987
suppression of proliferation of poliovirus and porcine parvovirus by novel phenoxazines, 2-amino-4,4 alpha-dihydro-4 alpha-7-dimethyl-3h-phenoxazine-3-one and 3-amino-1,4 alpha-dihydro-4 alpha-8-dimethyl-2h-phenoxazine-2-one.the present study aimed at investigating the antiviral effects of 2-amino-4,4alpha-dihydro-4alpha-7-dimethyl-3h-phenoxazine-3-one (phx-1) and 3-amino-1,4alpha-dihydro-4alpha-8-dimethyl-2h-phenoxazine-2-one (phx-2) on 6 representative viruses: poliovirus, porcine parvovirus, simian virus 40 (sv-40), herpes simplex virus-1 (hsv-1), sindbis virus, and vesicular stomatitis virus (vsv). phx-1 and phx-2 suppressed the proliferation of poliovirus in vero cells and that of porcine parvovirus in esk cell ...200515863903
induction of antigen-specific immune responses against malignant brain tumors by intramuscular injection of sindbis dna encoding gp100 and il-18.we constructed psin-sv40-hdv-sv40pa, an improved sindbis dna expression vector, and evaluated the potential of this vector system for brain tumor therapy. we investigated whether immunizing mice with xenogeneic dna encoding human gp100 and mouse il-18 would enhance the antitumor responses. to study the immune mechanisms involved in tumor regression, we examined tumor growth in b16-gp100-implanted brain tumor models using t-cell subset-depleted and ifn-gamma-neutralized mice. hugp100/mil-18 vacci ...200515869409
identification and phenotypic characterization of sphingomonas wittichii strain rw1 by peptide mass fingerprinting using matrix-assisted laser desorption ionization-time of flight mass spectrometry.mass spectrometry is a potentially attractive means of monitoring the survival and efficacy of bioaugmentation agents, such as the dioxin-mineralizing bacterium sphingomonas wittichii strain rw1. the biotransformation activity of rw1 phenotypes is determined primarily by the presence and concentration of the dioxin dioxygenase, an enzyme initiating the degradation of both dibenzo-p-dioxin and dibenzofuran (df). we explored the possibility of identifying and characterizing putative cultures of rw ...200515870332
properties of sindbis virus vectors produced with a chimeric split helper system.we have evaluated a chimeric, two-component sindbis virus packaging system. as expected, use of this combination of two modified helper rna species prevented formation of infection competent sindbis viruses as analyzed by serial passaging. we observed, however, that vectors produced using this method were able to spread in bhk cell cultures and formed clusters of transgene positive cells that did not display cytopathic effects for up to 3 days post-transduction. formation of spreading sindbis vi ...200515870906
clinical and laboratory manifestations of sindbis virus infection: prospective study, finland, 2002-2003.sindbis virus (sinv) is widespread in europe, africa, australia, and asia, but clinical infection occurs as epidemics in a few geographically restricted areas. we recently proved, by virus isolation from patients, that sinv is the causative agent of pogosta disease, a mosquito-borne rash-arthritis occurring as larger epidemics every seventh year in finland. altogether, 86 patients with serologically verified sinv infection were recruited to the present study during the 2002 outbreak. we now desc ...200515871114
persistent expression of factor viii in vivo following nonprimate lentiviral gene transfer.hemophilia a is a clinically important coagulation disorder caused by the lack or abnormality of plasma coagulation factor viii (fviii). gene transfer of the fviii cdna to hepatocytes using lentiviral vectors is a potential therapeutic approach. we investigated the efficacy of feline immunodeficiency virus (fiv)-based vectors in targeting hepatocytes and correcting fviii deficiency in a hemophilia a mouse model. several viral envelope glycoproteins were screened for efficient fiv vector pseudoty ...200515886327
long-range rna-rna interactions circularize the dengue virus genome.secondary and tertiary rna structures present in viral rna genomes play essential regulatory roles during translation, rna replication, and assembly of new viral particles. in the case of flaviviruses, rna-rna interactions between the 5' and 3' ends of the genome have been proposed to be required for rna replication. we found that two rna elements present at the ends of the dengue virus genome interact in vitro with high affinity. visualization of individual molecules by atomic force microscopy ...200515890901
the 5'-terminal region of the aichi virus genome encodes cis-acting replication elements required for positive- and negative-strand rna synthesis.aichi virus is a member of the family picornaviridae. it has already been shown that three stem-loop structures (sl-a, sl-b, and sl-c, from the 5' end) formed at the 5' end of the genome are critical elements for viral rna replication. in this study, we further characterized the 5'-terminal cis-acting replication elements. we found that an additional structural element, a pseudoknot structure, is formed through base-pairing interaction between the loop segment of sl-b (nucleotides [nt] 57 to 60) ...200515890931
characterization of human immunodeficiency virus gag-specific gamma interferon-expressing cells following protective mucosal immunization with alphavirus replicon particles.a safe, replication-defective viral vector that can induce mucosal and systemic immune responses and confer protection against many infectious pathogens, such as human immunodeficiency virus type 1 (hiv-1), may be an ideal vaccine platform. accordingly, we have generated and tested alphavirus replicon particles encoding hiv-1 gag from sindbis virus (sin-gag) and venezuelan equine encephalitis virus (vee-gag), as well as chimeras between the two (vee/sin-gag). following intramuscular (i.m.), intr ...200515890953
loss of interferon regulatory factor 3 in cells infected with classical swine fever virus involves the n-terminal protease, npro.we show that cells infected with the pestivirus classical swine fever virus (csfv) fail to produce alpha/beta interferon not only following treatment with double-stranded rna but also after superinfection with a heterologous virus, the alphavirus sindbis virus, a virus shown to normally induce interferon. we investigated whether the inhibition of interferon synthesis by csfv involved a block in interferon regulatory factor 3 (irf3) activity. cells infected with csfv exhibited a lack of transloca ...200515890962
secondary dengue virus type 4 infections in vietnam.this study was designated to describe clinical and biological features of patients with a suspected diagnosis of dengue fever/dengue hemorrhagic fever during an outbreak in central vietnam. one hundred and twenty-five consecutive patients hospitalized at khanh hoa and binh thuan provincial hospitals between november 2001 and january 2002 with a diagnosis of suspected dengue infection were included in the present study. viruses were isolated in c6/36 and vero e6 cell cultures or detected by rt-pc ...200515906664
rubella virus capsid protein modulation of viral genomic and subgenomic rna synthesis.the ratio of the subgenomic (sg) to genome rna synthesized by rubella virus (rub) replicons expressing the green fluorescent protein reporter gene (rubrep/gfp) is substantially higher than the ratio of these species synthesized by rub (4.3 for rubrep/gfp vs. 1.3-1.4 for rub). it was hypothesized that this modulation of the viral rna synthesis was by one of the virus structural protein genes and it was found that introduction of the capsid (c) protein gene into the replicons as an in-frame fusion ...200515907967
association of signr1 with tlr4-md-2 enhances signal transduction by recognition of lps in gram-negative bacteria.signr1, a member of a new family of mouse c-type lectins, is expressed at high levels in macrophages (mphi) within the splenic marginal zone, lymph node medulla, and in some strains, in peritoneal cavity. we previously reported that signr1 captures gram-negative bacteria, such as escherichia coli and salmonella typhimurium, as well as candida albicans. we have now investigated the precise ligands and innate responses that involve signr1. the interaction of signr1 with fitc-dextran and e. coli wa ...200515908446
no signalling decodes frequency of neuronal activity and generates synapse-specific plasticity in mouse cerebellum.nitric oxide (no) is an intercellular messenger regulating neuronal functions. to visualize no signalling in the brain, we generated a novel fluorescent no indicator, which consists of the heme-binding region (hbr) of soluble guanylyl cyclase and the green fluorescent protein. the indicator (hbr-gfp) was expressed in the purkinje cells of the mouse cerebellum and we imaged no signals in acute cerebellar slices upon parallel fibre (pf) activation with a train of burst stimulations (bs, each bs co ...200515919714
complement activation is required for induction of a protective antibody response against west nile virus infection.infection with west nile virus (wnv) causes a severe infection of the central nervous system (cns) with higher levels of morbidity and mortality in the elderly and the immunocompromised. experiments with mice have begun to define how the innate and adaptive immune responses function to limit infection. here, we demonstrate that the complement system, a major component of innate immunity, controls wnv infection in vitro primarily in an antibody-dependent manner by neutralizing virus particles in ...200515919902
noncytopathic replication of venezuelan equine encephalitis virus and eastern equine encephalitis virus replicons in mammalian cells.venezuelan equine encephalitis (vee) and eastern equine encephalitis (eee) viruses are important, naturally emerging zoonotic viruses. they are significant human and equine pathogens which still pose a serious public health threat. both vee and eee cause chronic infection in mosquitoes and persistent or chronic infection in mosquito-derived cell lines. in contrast, vertebrate hosts infected with either virus develop an acute infection with high-titer viremia and encephalitis, followed by host de ...200515919912
single amino acid insertions at the junction of the sindbis virus e2 transmembrane domain and endodomain disrupt virus envelopment and alter infectivity.the final steps in the envelopment of sindbis virus involve specific interactions of the e2 endodomain with the virus nucleocapsid. deleting e2 k at position 391 (e2 deltak391) resulted in the disruption of virus assembly in mammalian cells but not insect cells (host range mutant). this suggested unique interactions of the e2 deltak391 endodomain with the different biochemical environments of the mammalian and insect cell lipid bilayers. to further investigate the role of the amino acid residues ...200515919921
indoleamine 2,3-dioxygenase mediates cell type-specific anti-measles virus activity of gamma interferon.gamma interferon (ifn-gamma) has been shown to be increased in sera from patients with acute measles and after vaccination, to exhibit protective functions in brains of patients with subacute sclerosing panencephalitis, and to mediate a noncytolytic clearance of measles virus (mv) from rodent brains. in order to reveal a possible intracellular antiviral activity in the absence of antigen presentation and cytotoxic t cells, we investigated ifn-gamma-induced effects on mv replication in various ti ...200515919929
reversible acid-induced inactivation of the membrane fusion protein of semliki forest virus.previously, it has been shown that the exposure of semliki forest virus (sfv) to a mildly acidic environment induces a rapid and complete loss of the ability of the virus to bind and fuse to target membranes added subsequently. in the present study, incubation of sfv at low ph followed by a specific reneutralization step resulted in a partial reversion of this loss of viral fusion capacity, as assessed in a liposomal model system. also, the ability of the viral e1 fusion protein to undergo lipos ...200515919953
targeting sindbis virus-based vectors to fc receptor-positive cell types.some viruses display enhanced infection for fc receptor (fcr)-positive cell types when complexed with virus-specific immunoglobulin (ig). this process has been termed antibody-dependent enhancement of viral infection (ade). we reasoned that the mechanism of ade could be exploited and adapted to target alphavirus-based vectors to fcr-positive cell types. towards this goal, recombinant sindbis viruses were constructed that express 1 to 4 immunoglobulin-binding domains of protein l (ppl) as n-termi ...200515922395
california serogroup gc (g1) glycoprotein is the principal determinant of ph-dependent cell fusion and entry.members of the california serogroup of orthobunyaviruses, particularly la crosse (lac) and tahyna (tah) viruses, are significant human pathogens in areas where their mosquito vectors are endemic. previous studies using wild-type lac and tah181/57, a highly neurovirulent strain with low neuroinvasiveness (janssen, r., gonzalez-scarano, f., nathanson, n., 1984. mechanisms of bunyavirus virulence. comparative pathogenesis of a virulent strain of la crosse and an avirulent strain of tahyna virus. la ...200515923017
the use of gene silencing to study the role of dopa decarboxylase in mosquito melanization reactions.mosquito melanization involves hydroxylation of tyrosine to dopa, which then is oxidized to dopaquinone by phenoloxidase, or decarboxylated to dopamine by dopa decarboxlase (ddc). an armigeres subalbatus cdna encoding ddc was cloned and real-time pcr analysis revealed increased transcripts in blood-fed and microfilariae (mf)-inoculated mosquitoes. a double subgenomic sindbis virus was used to silence ddc and assess its role in melanization of mf. ddc transcription and activity were significantly ...200515926892
peptide inhibitors of dengue virus and west nile virus infectivity.viral fusion proteins mediate cell entry by undergoing a series of conformational changes that result in virion-target cell membrane fusion. class i viral fusion proteins, such as those encoded by influenza virus and human immunodeficiency virus (hiv), contain two prominent alpha helices. peptides that mimic portions of these alpha helices inhibit structural rearrangements of the fusion proteins and prevent viral infection. the envelope glycoprotein (e) of flaviviruses, such as west nile virus ( ...200515927084
design, synthesis, and evaluation of dioxane-based antiviral agents targeted against the sindbis virus capsid protein.dioxane-based antiviral agents targeted to the hydrophobic binding pocket of sindbis virus capsid protein were designed by computer graphics molecular modeling and synthesized. virus production using sin-ires-luc and capsid assembly were monitored to evaluate antiviral activity. a compound with a three-carbon linker chain connecting two dioxane moieties inhibited virus production by 50% at a concentration of 40 microm, while (r)-hydroxymethyldioxane inhibited virus production by 50% at a concent ...200515927464
interferon and cytomegalovirus in vivo and in vitro. 196715938281
rab7 associates with early endosomes to mediate sorting and transport of semliki forest virus to late endosomes.semliki forest virus (sfv) is internalized by clathrin-mediated endocytosis, and transported via early endosomes to late endosomes and lysosomes. the intracellular pathway taken by individual fluorescently labeled sfv particles was followed using immunofluorescence in untransfected cells, and by video-enhanced, triple-color fluorescence microscopy in live cells transfected with gfp- and rfp-tagged rab5, rab7, rab4, and arf1. the viruses progressed from rab5-positive early endosomes to a populati ...200515954801
enhanced potency of plasmid dna microparticle human immunodeficiency virus vaccines in rhesus macaques by using a priming-boosting regimen with recombinant proteins.dna vaccines have been used widely in experimental primate models of human immunodeficiency virus (hiv), but their effectiveness has been limited. in this study, we evaluated three technologies for increasing the potency of dna vaccines in rhesus macaques. these included dna encoding sindbis virus rna replicons (psincp), cationic poly(lactide-co-glycolide) (plg) microparticles for dna delivery, and recombinant protein boosting. the dna-based psincp replicon vaccines encoding hiv gag and env were ...200515956564
innate stat1-dependent genomic response of neurons to the antiviral cytokine alpha interferon.alpha/beta interferons (ifns-alpha/beta) are cytokines that play an essential role in the host defense against viral infection. our previous studies have shown that the key ifn signaling molecule stat1 is highly elevated and activated in central nervous system neurons during viral infection and in transgenic mice with astrocyte production of ifn-alpha (glial fibrillary acidic protein [gfap]-ifn-alpha), suggesting that neurons are a very responsive target cell population for ifns. to elucidate th ...200515956575
control of translation by the 5'- and 3'-terminal regions of the dengue virus genome.the genomic rnas of flaviviruses such as dengue virus (den) have a 5' m7gpppn cap like those of cellular mrnas but lack a 3' poly(a) tail. we have studied the contributions to translational expression of 5'- and 3'-terminal regions of the den serotype 2 genome by using luciferase reporter mrnas transfected into vero cells. dcld rna contained the entire den 5' and 3' untranslated regions (utrs), as well as the first 36 codons of the capsid coding region fused to the luciferase reporter gene. capp ...200515956576
envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 west nile virus strains.the introduction of west nile virus (wnv) into north america has been associated with relatively high rates of neurological disease and death in humans, birds, horses, and some other animals. previous studies identified strains in both genetic lineage 1 and genetic lineage 2, including north american isolates of lineage 1, that were highly virulent in a mouse neuroinvasion model, while other strains were avirulent or significantly attenuated (d. w. c. beasley, l. li, m. t. suderman, and a. d. t. ...200515956579
early arthritis and summarize the recent literature on the association of infection with early arthritis, and to discuss the possible role of such infections with respect to the development of chronic rheumatic complications.200515956840
oncolytic viral therapy for cervical and ovarian cancer cells by sindbis virus ar339 strain.recently, the application of replication-competent viruses has been studied as anticancer agents. sindbis virus (sin) is an rna virus that belongs to the alphavirus genus in the togaviridae virus family. the ar339 strain of sin has not been reported to induce any serious disease to humans.200515958641
viroporin activity of murine hepatitis virus e protein.the viroporin activity of the e protein from murine hepatitis virus (mhv), a member of the coronaviruses, was analyzed. viroporins are a growing family of viral proteins able to enhance membrane permeability, promoting virus budding. initially, the mhv e gene was inducibly expressed in escherichia coli cells, leading to the arrest of bacterial growth, cell lysis and permeabilization to different compounds. thus, exit of labeled nucleotides from e. coli cells to the cytoplasm was apparent upon ex ...200515963987
targeted gene delivery by intravenous injection of retroviral vectors.specifically and effectively directing a therapeutic gene to its intended site of action is a critical issue for translation of basic genomics to clinical gene therapy. delivering gene therapy vectors to specific cells or tissues through intravenous injection is the most desirable method for this purpose. in 2001, we reported successful targeted gene transduction in vitro utilizing both oncoretroviral and lentiviral vectors pseudotyped with a chimeric sindbis virus envelope (zz sindbis). however ...200515970695
castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo.previous studies have suggested that alpha-glucosidase inhibitors such as castanospermine and deoxynojirimycin inhibit dengue virus type 1 infection by disrupting the folding of the structural proteins prm and e, a step crucial to viral secretion. we extend these studies by evaluating the inhibitory activity of castanospermine against a panel of clinically important flaviviruses including all four serotypes of dengue virus, yellow fever virus, and west nile virus. using in vitro assays we demons ...200515994763
infectious pancreatic necrosis virus vp5 is dispensable for virulence and persistence.infectious pancreatic necrosis virus (ipnv) is the causative agent of infectious pancreatic necrosis (ipn) disease in salmonid fish. recent studies have revealed variation in virulence between isolates of the sp serotype, associated with certain residues of the structural protein vp2. the isolates are also highly heterogenic in the coding region of the nonstructural vp5 protein. to study the involvement of this protein in the pathogenesis of disease, we generated three recombinant vp5 mutant vir ...200515994815
respiratory syncytial virus nonstructural proteins ns1 and ns2 mediate inhibition of stat2 expression and alpha/beta interferon responsiveness.respiratory syncytial virus (rsv) subverts the antiviral interferon (ifn) response, but the mechanism for this evasion was unclear. here we show that rsv preferentially inhibits ifn-alpha/beta signaling by expression of viral ns1 and ns2. thus, rsv infection or expression of recombinant ns1 and ns2 in epithelial host cells causes a marked decrease in stat2 levels and the consequent downstream ifn-alpha/beta response. similarly, ns1/ns2-deficient rsv no longer decreases stat2 levels or ifn respon ...200515994826
aif suppresses chemical stress-induced apoptosis and maintains the transformed state of tumor cells.apoptosis-inducing factor (aif) exhibits reactive oxygen species (ros)-generating nadh oxidase activity of unknown significance, which is dispensable for apoptosis. we knocked out the aif gene in two human colon carcinoma cell lines that displayed lower mitochondrial complex i oxidoreductase activity and produced less ros, but showed increased sensitivity to peroxide- or drug-induced apoptosis. aif knockout cells failed to form tumors in athymic mice or grow in soft agar. only aif with intact na ...200516001080
reovirus infection of the cns enhances inos expression in areas of virus-induced injury.nitric oxide (no) has been implicated as a contributor to the host's innate defense against viral infections including those affecting the cns. reovirus infection of the cns is a classic experimental system for understanding the pathogenesis of neurotropic viral infection. infection with serotype 3 strains is associated with perturbations in various cellular signaling pathways including nf-kappab and no plays a regulatory role in many of these same pathways. we therefore examined whether no prod ...200516004984
inhibition of transcription and translation in sindbis virus-infected cells.alphaviruses are arthropod-borne viruses (arboviruses) that include a number of important human and animal pathogens. the natural transmission cycle of alphaviruses requires their presence at high concentrations in the blood of amplification hosts for efficient infection of mosquito vectors. the high-titer viremia development implies multiple rounds of infection that proceed in the background of the developing antiviral cell response aimed at blocking virus spread on an organismal level. therefo ...200516014903
characterization of immune responses induced by intramuscular vaccination with dna vaccines encoding measles virus hemagglutinin and/or fusion proteins.measles virus (mv) hemagglutinin (mv-h) and fusion (mv-f) proteins induce plaque reduction neutralizing (prn) antibodies and cell-mediated immune responses that protect against clinical measles. dna vaccines that encode mv-h and mv-f are being investigated as a new generation of measles vaccine to protect infants too young to receive currently licensed attenuated measles vaccines. however, it is unclear whether dna vaccines encoding both mv-h and mv-f act synergistically to induce stronger immun ...200516014946
essential amino acids of the hantaan virus n protein in its interaction with rna.the nucleocapsid (n) protein of hantavirus encapsidates viral genomic and antigenomic rnas. previously, deletion mapping identified a central, conserved region (amino acids 175 to 217) within the hantaan virus (htnv) n protein that interacts with a high affinity with these viral rnas (vrnas). to further define the boundaries of the rna binding domain (rbd), several peptides were synthesized and examined for the ability to bind full-length s-segment vrna. peptide 195-217 retained 94% of the vrna ...200516014963
modulation of disease, t cell responses, and measles virus clearance in monkeys vaccinated with h-encoding alphavirus replicon particles.measles remains a major worldwide problem partly because of difficulties with vaccination of young infants. new vaccine strategies need to be safe and to provide sustained protective immunity. we have developed sindbis virus replicon particles that express the measles virus (mv) hemagglutinin (sin-h) or fusion (sin-f) proteins. in mice, sin-h induced high-titered, dose-dependent, mv-neutralizing antibody after a single vaccination. sin-f, or sin-h and sin-f combined, induced somewhat lower respo ...200516037211
bcl-xl inhibits t-cell apoptosis induced by expression of sars coronavirus e protein in the absence of growth of the hallmark findings in patients suffering from sars (severe acute respiratory syndrome) is lymphopenia, which is the result of massive lymphocyte death. sars-cov (sars coronavirus), a novel coronavirus that has been etiologically associated with sars cases, is homologous with mhv (murine hepatitis coronavirus), and mhv small envelope e protein is capable of inducing apoptosis. we hypothesized that sars-cov encodes a small envelope e protein that is homologous with mhv e protein, thus in ...200516048439
early alpha/beta interferon production by myeloid dendritic cells in response to uv-inactivated virus requires viral entry and interferon regulatory factor 3 but not myd88.alpha/beta interferons (ifn-alpha/beta) are key mediators of innate immunity and important modulators of adaptive immunity. the mechanisms by which ifn-alpha/beta are induced are becoming increasingly well understood. recent studies showed that toll-like receptors 7 and 8 expressed by plasmacytoid dendritic cells (pdcs) mediate the endosomal recognition of incoming viral rna genomes, a process which requires myeloid differentiation factor 88 (myd88). here we investigate the requirements for viru ...200516051830
bovine viral diarrhea virus entry is dependent on clathrin-mediated endocytosis.cellular mechanisms of bovine viral diarrhea virus (bvdv) entry in mdbk cells were investigated. chloroquine, bafilomycin a1, or ammonium chloride inhibited bvdv infection, indicating that an acidic endosomal ph is required for bvdv entry. the tyrosine kinase inhibitor genistein partially inhibited bvdv infection at a postentry step, whereas bvdv entry was strongly inhibited by chlorpromazine or by the overexpression of a dominant-negative form of eps15, a protein essential for the formation of ...200516051874
pkcdelta-mediated regulation of flip expression in human colon cancer cells.flice-like inhibitory protein (flip), a naturally occurring caspase-inhibitory protein that lacks the critical cysteine domain necessary for catalytic activity, is a negative regulator of fas-induced apoptosis. decreased flip levels sensitize tumor cells to fas- and trail-mediated apoptosis; however, the cellular mechanisms regulating flip expression have not been defined. here, we examined the roles of the pkc and nf-kappab pathway in the regulation of flip in human colon cancers. flip mrna lev ...200616052516
a family of mammalian e3 ubiquitin ligases that contain the ubr box motif and recognize n-degrons.a subset of proteins targeted by the n-end rule pathway bear degradation signals called n-degrons, whose determinants include destabilizing n-terminal residues. our previous work identified mouse ubr1 and ubr2 as e3 ubiquitin ligases that recognize n-degrons. such e3s are called n-recognins. we report here that while double-mutant ubr1(-/-) ubr2(-/-) mice die as early embryos, the rescued ubr1(-/-) ubr2(-/-) fibroblasts still retain the n-end rule pathway, albeit of lower activity than that of w ...200516055722
viruses activate a genetically conserved cell death pathway in a unicellular organism.given the importance of apoptosis in the pathogenesis of virus infections in mammals, we investigated the possibility that unicellular organisms also respond to viral pathogens by activating programmed cell death. the m1 and m2 killer viruses of saccharomyces cerevisiae encode pore-forming toxins that were assumed to kill uninfected yeast cells by a nonprogrammed assault. however, we found that yeast persistently infected with these killer viruses induce a programmed suicide pathway in uninfecte ...200516061692
a cell-free system for the synthesis of sindbis virus subgenomic rna: importance of the concentration of the initiating ntp.we describe here an in vitro system for template-dependent initiation and synthesis of a sindbis virus (sv) subgenomic (sg) rna transcript. the critical components of this system were (1) a minus-strand promoter-template corresponding to the region of the sv genome from nt 7441 to nt 7772 (-157 to +175 relative to the sg rna transcription initiation site at nt 7598), and (2) a p15 fraction from cells infected with recombinant vaccinia viruses expressing the sv nonstructural proteins, p123 and ns ...200516085228
profile of diane e. griffin. 200516087864
altering the tropism of lentiviral vectors through pseudotyping.the host range of retroviral vectors including lentiviral vectors can be expanded or altered by a process known as pseudotyping. pseudotyped lentiviral vectors consist of vector particles bearing glycoproteins (gps) derived from other enveloped viruses. such particles possess the tropism of the virus from which the gp was derived. for example, to exploit the natural neural tropism of rabies virus, vectors designed to target the central nervous system have been pseudotyped using rabies virus-deri ...200516101513
variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus.eastern equine encephalitis virus (eeev) causes human encephalitis in north america (na), but in south america (sa) it has rarely been associated with human disease, suggesting that sa strains are less virulent. to evaluate the hypothesis that this virulence difference is due to a greater ability of na strains to evade innate immunity, we compared replication of na and sa strains in vero cells pretreated with interferon (ifn). human ifn-alpha, -beta, and -gamma generally exhibited less effect on ...200516103182
state-dependent ras signaling and ampa receptor trafficking.synaptic trafficking of ampa-rs, controlled by small gtpase ras signaling, plays a key role in synaptic plasticity. however, how ras signals synaptic ampa-r trafficking is unknown. here we show that low levels of ras activity stimulate extracellular signal-regulated kinase kinase (mek)-p42/44 mapk (extracellular signal-regulated kinase [erk]) signaling, whereas high levels of ras activity stimulate additional pi3 kinase (pi3k)-protein kinase b (pkb) signaling, each accounting for approximately 5 ...200516107614
local translation of rhoa regulates growth cone collapse.neuronal development requires highly coordinated regulation of the cytoskeleton within the developing axon. this dynamic regulation manifests itself in axonal branching, turning and pathfinding, presynaptic differentiation, and growth cone collapse and extension. semaphorin 3a (sema3a), a secreted guidance cue that primarily functions to repel axons from inappropriate targets, induces cytoskeletal rearrangements that result in growth cone collapse. these effects require intra-axonal messenger rn ...200516107849
identification of amino acids of sindbis virus e2 protein involved in targeting tumor metastases in vivo.previous studies conducted in our laboratory with sindbis viral vectors in animal models demonstrated excellent in vivo targeting of tumor cells and significant reduction of metastatic implant size. to explore the influence of sindbis strain on these factors, we constructed new plasmids from the wild-type ar-339 sindbis virus strain and compared their sequences. we found differences in the replicase and envelope proteins between jt, hrsp, and ar-339 sequences. we made chimeras combining both str ...200516109508
infection of dendritic cells by a gamma2-herpesvirus induces functional modulation.the murine gamma-herpesvirus-68 (gammahv68) establishes viral latency in dendritic cells (dcs). in the present study, we examined the specific consequences of dc infection by gammahv68, both in vivo and in vitro. ex vivo analysis of infected mice showed that the virus colonizes respiratory dcs very early after infection and that all subsets of splenic dcs analyzed are viral targets. we have developed and characterized an in vitro model of gammahv68 infection of dcs. using this model, we demonstr ...200516116213
hybrid sindbis/epstein-barr virus episomal expression vector for inducible production of proteins.alphavirus vectors are attractive as recombinant protein expression systems due to the high level of gene expression achieved. the combination of two mutations in the viral replicase, which render the replicase noncytopathic and temperature-sensitive, allowed the generation of a dna-based vector (cytts) that shows temperature inducible expression. this vector is of significant value for the production of toxic protein. however, like for other stable expression systems, tedious screening of indiv ...200516116794
quantification of different human alpha interferon subtypes and pegylated interferon activities by measuring mxa promoter activation.alpha interferons (alpha-ifns) are potent biologically active proteins synthesized and secreted by somatic cells during viral infection. quantification of alpha-ifn concentrations in biological samples is used for diagnosis. more recently, recombinant ifns have been used as antiviral, antiproliferative, and immunomodulatory therapeutic agents, and particularly for the treatment of chronic hepatitis c virus infection. for this purpose, ifn has recently been coupled to polyethylene glycol (peg) to ...200516127052
a novel ca2+ indicator protein using fret and calpain-sensitive, we report the properties of a fret-based calcium indicator protein. we constructed a tandem fusion protein, named f2c, of ecfp and eyfp combined with calpain-sensitive sequences of alpha-spectrin, with n-terminal palmitoylation signal of gap-43. it was previously reported that calpain cleaved a similar ecfp-eyfp fusion protein linked by a calpain-sensitive sequence of alpha-spectrin (fodrin). unexpectedly, f2c was not cleaved by calpain, but demonstrated properties of a ca(2+) indicator wh ...200516129417
pick1 is a calcium-sensor for nmda-induced ampa receptor trafficking.regulation of ampa receptor (ampar) trafficking results in changes in receptor number at the postsynaptic membrane, and hence modifications in synaptic strength, which are proposed to underlie learning and memory. nmda receptor-mediated postsynaptic ca2+ influx enhances ampar internalisation, but the molecular mechanisms that trigger such trafficking are not well understood. we investigated whether ampar-associated protein-protein interactions known to regulate receptor surface expression may be ...200516138078
kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal ca1 pyramidal neurones.a-type potassium channels regulate neuronal firing frequency and the back-propagation of action potentials (aps) into dendrites of hippocampal ca1 pyramidal neurones. recent molecular cloning studies have found several families of voltage-gated k(+) channel genes expressed in the mammalian brain. at present, information regarding the relationship between the protein products of these genes and the various neuronal functions performed by voltage-gated k(+) channels is lacking. here we used a comb ...200516141270
critical roles for both stat1-dependent and stat1-independent pathways in the control of primary dengue virus infection in mice.dengue virus (den), a flavivirus, causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, the most common mosquito-borne viral illnesses in humans worldwide. in this study, using stat1(-/-) mice bearing two different mutant stat1 alleles in the 129/sv/ev background, we demonstrate that ifnr-dependent control of primary den infection involves both stat1-dependent and stat1-independent mechanisms. the stat1 pathway is necessary for clearing the initial viral load, whereas the stat1 ...200516148142
carbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins.defensins are peptides that protect the host against microorganisms. here we show that the theta-defensin retrocyclin 2 (rc2) inhibited influenza virus infection by blocking membrane fusion mediated by the viral hemagglutinin. rc2 was effective even after hemagglutinin attained a fusogenic conformation or had induced membrane hemifusion. rc2, a multivalent lectin, prevented hemagglutinin-mediated fusion by erecting a network of crosslinked and immobilized surface glycoproteins. rc2 also inhibite ...200516155572
both antigen optimization and lysosomal targeting are required for enhanced anti-tumour protective immunity in a human papillomavirus e7-expressing animal tumour model.dna immunization is a new approach for cancer immune therapy. in this study, we constructed human papillomavirus (hpv) 16 e7 expression vector cassettes and then compared the abilities of these constructs to induce antitumour protection. lysosome-targeted e7 antigens, and to a lesser degree signal sequence-conjugated and transmembrane region sequence-conjugated e7 antigens in a dna form, displayed tumour protection significantly higher than wild-type e7 antigens. this enhanced tumour protection ...200516162274
prime-boost vaccination with plasmid and adenovirus gene vaccines control her2/neu+ metastatic breast cancer in mice.once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for her2/neu. a vaccine targeting p185, the protein product of the her2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive her2/neu+ cells. the purpose of this study was to determine the effectiveness of two gene vaccines targeting her2/neu in preventive and therapeutic tumor models.200516168101
evaluation of cis-acting elements in the rubella virus subgenomic rna that play a role in its translation.the subgenomic (sg) mrna of rubella virus (rub) contains the structural protein open reading frame (sp-orf) that is translated to produce the three virion structural proteins: capsid (c) and glycoproteins e2 and e1. rub expression vectors have been developed that express heterologous genes from the sg rna, including replicons which replace the sp-orf with a heterologous gene, and these expression vectors are candidate vaccine vectors. in the related alphaviruses, translational enhancing elements ...200616172842
adp-ribose-1"-monophosphatase: a conserved coronavirus enzyme that is dispensable for viral replication in tissue culture.replication of the approximately 30-kb plus-strand rna genome of coronaviruses and synthesis of an extensive set of subgenome-length rnas are mediated by the replicase-transcriptase, a membrane-bound protein complex containing several cellular proteins and up to 16 viral nonstructural proteins (nsps) with multiple enzymatic activities, including protease, polymerase, helicase, methyltransferase, and rnase activities. to get further insight into the replicase gene-encoded functions, we characteri ...200516188975
virus infection switches tlr-3-positive human neurons to become strong producers of beta study the capacity of human neurons to mount innate immunity responses to viral infections, we infected cells of a human postmitotic neuron-derivative cell line, nt2-n, with rabies virus (rabv) and herpes simplex type 1 (hsv-1). changes in neuronal gene expression were analyzed by use of affymetrix microarrays. applying a twofold cutoff, rabv increased the transcription of 228 genes, and hsv-1 increased the transcription of 263 genes. the most striking difference between the two infections co ...200516188991
a surface groove essential for viral bcl-2 function during chronic infection in vivo.antiapoptotic bcl-2 family proteins inhibit apoptosis in cultured cells by binding bh3 domains of proapoptotic bcl-2 family members via a hydrophobic bh3 binding groove on the protein surface. we investigated the physiological importance of the bh3 binding groove of an antiapoptotic bcl-2 protein in mammals in vivo by analyzing a viral bcl-2 family protein. we show that the gamma-herpesvirus 68 (gammahv68) bcl-2 family protein (gammahv68 v-bcl-2), which is known to inhibit apoptosis in cultured ...200516201011
sindbis virus induces transport processes and alters expression of innate immunity pathway genes in the midgut of the disease vector, aedes aegypti.the midgut of hematophagous insects is the initial site of infection by arthropod-borne viruses (arboviruses) and plays a crucial role in vector competence. to further understand processes that occur in the midgut in response to infection by an arbovirus, dna microarrays were used to analyze gene expression changes following infection by the alphavirus, sindbis (mre16 malaysian strain). midgut transcription profiles from mosquitoes fed blood containing 10(8)pfu/ml of virus were compared with tho ...200516203210
domain iii from class ii fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion.alphaviruses and flaviviruses infect cells through low ph-dependent membrane fusion reactions mediated by their structurally similar viral fusion proteins. during fusion, these class ii viral fusion proteins trimerize and refold to form hairpin-like structures, with the domain iii and stem regions folded back toward the target membrane-inserted fusion peptides. we demonstrate that exogenous domain iii can function as a dominant-negative inhibitor of alphavirus and flavivirus membrane fusion and ...200516216925
ceramide-enriched membrane domains.cellular activation involves the re-organization of receptor molecules and the intracellular signalosom in the cell membrane. recent studies indicate that specialized domains of the cell membrane, termed rafts, are central for the spatial organization of receptors and signaling molecules. rafts are converted into larger membrane platforms by activity of the acid sphingomyelinase, which hydrolyses raft-sphingomyelin to ceramide. ceramide molecules spontaneously associate to form ceramide-enriched ...200516226325
alpha/beta interferon protects against lethal west nile virus infection by restricting cellular tropism and enhancing neuronal survival.west nile virus (wnv) is a mosquito-borne flavivirus that is neurotropic in humans, birds, and other animals. while adaptive immunity plays an important role in preventing wnv spread to the central nervous system (cns), little is known about how alpha/beta interferon (ifn-alpha/beta) protects against peripheral and cns infection. in this study, we examine the virulence and tropism of wnv in ifn-alpha/beta receptor-deficient (ifn- alpha/betar-/-) mice and primary neuronal cultures. ifn-alpha/beta ...200516227257
cd8 t cells require gamma interferon to clear borna disease virus from the brain and prevent immune system-mediated neuronal damage.borna disease virus (bdv) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain mrl. disease does not result from the virus-induced destruction of infected neurons. rather, it is mediated by h-2(k)-restricted antiviral cd8 t cells that recognize a peptide derived from the bdv nucleoprotein n. persistent bdv infection in mice is not spontaneously cleared. we report here that n-specific vaccination can protect wild-type mrl mice but not mutant mrl ...200516227271
influenza virus hemagglutinin (h3 subtype) requires palmitoylation of its cytoplasmic tail for assembly: m1 proteins of two subtypes differ in their ability to support assembly.the influenza a virus hemagglutinin (ha) transmembrane domain boundary region and the cytoplasmic tail contain three cysteines (residues 555, 562, and 565 for the h3 ha subtype) that are highly conserved among the 16 ha subtypes and which are each modified by the covalent addition of palmitic acid. previous analysis of the role of these conserved cysteine residues led to differing data, suggesting either no role for ha palmitoylation or an important role for ha palmitoylation. to reexamine the r ...200516227287
human immunodeficiency virus type 1 vpr interacts with antiapoptotic mitochondrial protein hax-1.human immunodeficiency virus type 1 viral protein r (vpr) is required for viral pathogenesis and has been implicated in t-cell apoptosis through its activation of caspase 3 and caspase 9 and perturbation of mitochondrial membrane potential. to understand better vpr-mitochondria interaction, we report here the identification of antiapoptotic mitochondrial protein hax-1 as a novel vpr target. we show that vpr and hax-1 physically associate with each other. overexpression of vpr in cells dislocates ...200516227293
aberrant cortical neurogenesis in a pediatric neuroaids model: neurotrophic effects of growth study the effects of hiv-1 and feline immunodeficiency virus (fiv) on neural stem cell viability, together with the neurotrophic properties of growth hormone (gh) in models of pediatric neuroaids.200516227785
biology and application of alphaviruses in gene therapy.the broad host cell range and high expression levels of transgenes are features that have made alphaviruses attractive for gene expression studies and gene therapy applications. particularly, semliki forest virus vectors have been applied for large-scale production of recombinant membrane proteins for drug screening purposes and structural biology studies. the high preference of expression in neuronal cells has led to many applications of alphavirus vectors in neuroscience. studies on localizati ...200516231060
the efficient packaging of venezuelan equine encephalitis virus-specific rnas into viral particles is determined by nsp1-3 synthesis.alphaviruses are regarded as attractive systems for expression of heterologous genes and development of recombinant vaccines. venezuelan equine encephalitis virus (vee)-based vectors are particularly promising because of their specificity to lymphoid tissues and strong resistance to interferon. to improve understanding of the vee genome packaging and optimize application of this virus as a vector, we analyzed in more detail the mechanism of packaging of the vee-specific rnas. the presence of the ...200616239019
vaccination with a sindbis virus-based dna vaccine expressing antigen 85b induces protective immunity against mycobacterium improve dna vaccination against mycobacterium tuberculosis, we evaluated the effectiveness of a sindbis virus-based dna construct expressing the tuberculosis antigen 85b (sin85b). the protective efficacy of sin85b was initially assessed by aerogenically challenging immunized c57bl/6 mice with virulent mycobacterium tuberculosis. at 1 and 7 months postinfection, the lung bacterial burdens were considerably reduced and the lung pathology was improved in vaccinated mice compared to naive control ...200516239577
fluorescent labeling of rat auditory brainstem circuits for synaptic and electrophysiological studies.we visualized neurons with fluorescent agents, both retrogradely and anterogradely, to identify the input and output neuronal pathways in the rat auditory system. output neurons of dorsal cochlear nucleus (dcn) were labeled retrogradely by injecting fluorescent microspheres into the inferior colliculus. electrical recordings were made from the labeled fusiform cells of dcn with the whole-cell patch-clamp recording technique in slice preparations. dii and sindbis virus expressing membrane-targete ...200616246426
stress-activated protein kinases are involved in coxsackievirus b3 viral progeny release.stress-activated protein kinases (sapks), consisting of c-jun n-terminal kinase (jnk) and p38 mitogen-activated protein kinase (p38 mapk), are activated upon various environmental stimuli, including viral infections. cellular survival and death signaling events following coxsackievirus b3 (cvb3) infection have been studied in relationship to viral replication, but the role of sapks has not been scrutinized. in this study, we found that the phosphorylation of jnk1/2 and p38 mapk was increased dur ...200516254323
identification of interferon-stimulated gene 15 as an antiviral molecule during sindbis virus infection in vivo.the innate immune response, and in particular the alpha/beta interferon (ifn-alpha/beta) system, plays a critical role in the control of viral infections. interferons alpha and beta exert their antiviral effects through the induction of hundreds of interferon-induced (or -stimulated) genes (isgs). while several of these isgs have characterized antiviral functions, their actions alone do not explain all of the effects mediated by ifn-alpha/beta. to identify additional ifn-induced antiviral molecu ...200516254333
alpha/beta interferons regulate murine gammaherpesvirus latent gene expression and reactivation from latency.alpha/beta interferon (ifn-alpha/beta) protects the host from virus infection by inhibition of lytic virus replication in infected cells and modulation of the antiviral cell-mediated immune response. to determine whether ifn-alpha/beta also modulates the virus-host interaction during latent virus infection, we infected mice lacking the ifn-alpha/beta receptor (ifn-alpha/betar(-/-)) and wild-type (wt; 129s2/svpas) mice with murine gammaherpesvirus 68 (gammahv68), a lymphotropic gamma-2-herpesviru ...200516254350
effect of alternating passage on adaptation of sindbis virus to vertebrate and invertebrate cells.mosquito-borne alphaviruses, which replicate alternately and obligately in mosquitoes and vertebrates, appear to experience lower rates of evolution than do many rna viruses that replicate solely in vertebrates. this genetic stability is hypothesized to result from the alternating host cycle, which constrains evolution by imposing compromise fitness solutions in each host. to test this hypothesis, sindbis virus was passaged serially, either in one cell type to eliminate host alteration or altern ...200516254360
[the ecology and prevalence of arboviruses on the territory of the saratov region].the territorial spread of tahyna, batai, sindbis, west nile fever and crimean-congo hemorrhagic fever viruses throughout the saratov region in 1998 - 2000 was analyzed. the characteristics of the epizootic activity of the natural foci of these arboviruses in different landscape zones (temperate forest-steppes, steppes and semi-deserts) were calculated. the species composition of small mammals, the natural reservoirs of the causative agents of arbovirus infections, was determined.200516279530
endocytosis and a low-ph step are required for productive entry of equine infectious anemia virus.recently, it has become evident that entry of some retroviruses into host cells is dependent upon a vesicle-localized, low-ph step. the entry mechanism of equine infectious anemia virus (eiav) has yet to be examined. here, we demonstrate that wild-type strains of eiav require a low-ph step for productive entry. lysosomotropic agents that inhibit the acidification of internal vesicles inhibited productive entry of eiav. the presence of ammonium chloride (30 mm), monensin (30 microm), or bafilomyc ...200516282447
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