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immune response during acute chandipura viral infection in experimentally infected susceptible mice.age dependent susceptibility was observed in chandipura virus (chpv) infected mice through intravenous and intraperitoneal route. adult mice were susceptible only through intracerebral route of infection. immature neuron and some other biological variables including immature immune system are considered to be important factor for age related susceptibility in some diseases. as chandipura virus infects both young and adult mice brain through intracerebral route the role of immune system during pe ...200818937835
bidirectional regulation of kainate receptor surface expression in hippocampal neurons.kainate receptors (kars) are crucial for the regulation of both excitatory and inhibitory neurotransmission, but little is known regarding the mechanisms controlling kar surface expression. we used super ecliptic phluorin (sep)-tagged kar subunit glur6a to investigate real-time changes in kar surface expression in hippocampal neurons. sindbis virus-expressed sep-glur6 subunits efficiently co-assembled with native kar subunits to form heteromeric receptors. diffuse surface-expressed dendritic sep ...200818955488
a protein that replaces the entire cellular eif4f complex.the eif4f cap-binding complex mediates the initiation of cellular mrna translation. eif4f is composed of eif4e, which binds to the mrna cap, eif4g, which indirectly links the mrna cap with the 43s pre-initiation complex, and eif4a, which is a helicase necessary for initiation. viral nucleocapsid proteins (n) function in both genome replication and rna encapsidation. surprisingly, we find that hantavirus n has multiple intrinsic activities that mimic and substitute for each of the three peptides ...200818971945
genome 3'-end repair in dengue virus type 2.genomes of rna viruses encounter a continual threat from host cellular ribonucleases. therefore, viruses have evolved mechanisms to protect the integrity of their genomes. to study the mechanism of 3'-end repair in dengue virus-2 in mammalian cells, a series of 3'-end deletions in the genome were evaluated for virus replication by detection of viral antigen ns1 and by sequence analysis. limited deletions did not cause any delay in the detection of ns1 within 5 d. however, deletions of 7-10 nucle ...200818974278
size alters susceptibility of vectors to dengue virus infection and dissemination.the size of arthropod vectors may affect their ability to transmit pathogens. here we test the hypothesis that body size alters the susceptibility of aedes aegypti and aedes albopictus mosquitoes to dengue virus (denv) infection and subsequent dissemination throughout the body of the mosquito. after feeding on blood containing known quantities of virus, smaller-sized females were significantly more likely to become infected and to disseminate virus than larger individuals. the effects of size we ...200818981505
ex vivo promoter analysis of antiviral heat shock cognate 70b gene in anopheles gambiae.the anopheles gambiae heat shock cognate gene (hsc70b) encodes a constitutively expressed protein in the hsp70 family and it functions as a molecular chaperone for protein folding. however, the expression of hsc70b can be further induced by certain stimuli such as heat shock and infection. we previously demonstrated that the an. gambiae hsc70b is induced during o'nyong-nyong virus (onnv) infection and subsequently suppresses onnv replication in the mosquito. to further characterize the inducibil ...200818986525
therapeutic and prophylactic applications of alphavirus vectors.alphavirus vectors are high-level, transient expression vectors for therapeutic and prophylactic use. these positive-stranded rna vectors, derived from semliki forest virus, sindbis virus and venezuelan equine encephalitis virus, multiply and are expressed in the cytoplasm of most vertebrate cells, including human cells. part of the genome encoding the structural protein genes, which is amplified during a normal infection, is replaced by a transgene. three types of vector have been developed: vi ...200819000329
genetic determinants of sindbis virus mosquito infection are associated with a highly conserved alphavirus and flavivirus envelope sequence.wild-type sindbis virus (sinv) strain mre16 efficiently infects aedes aegypti midgut epithelial cells (mec), but laboratory-derived neurovirulent sinv strain te/5'2j infects mec poorly. sinv determinants for mec infection have been localized to the e2 glycoprotein. the e2 amino acid sequences of mre16 and te/5'2j differ at 60 residue sites. to identify the genetic determinants of mec infection of mre16, the te/5'2j virus genome was altered to contain either domain chimeras or more focused nucleo ...200818160430
cis- and trans-acting functions of brome mosaic virus protein 1a in genomic rna1 replication.rna viruses employ a combination of mechanisms to regulate their gene expression and replication. brome mosaic virus (bmv) is a tripartite positive-strand rna virus used to study the requirements for virus infection. bmv genomic rna1 encodes protein 1a, which contains a methyltransferase (mt) domain and a helicase domain that are required for replication. 1a forms a complex with the 2a rna-dependent rna polymerase for the replication and transcription of all bmv rnas. rna1 expressed with 2a from ...200818160434
alpha/beta interferon inhibits cap-dependent translation of viral but not cellular mrna by a pkr-independent mechanism.the alpha/beta interferon (ifn-alpha/beta) response is critical for host protection against disseminated replication of many viruses, primarily due to the transcriptional upregulation of genes encoding antiviral proteins. previously, we determined that infection of mice with sindbis virus (sb) could be converted from asymptomatic to rapidly fatal by elimination of this response (k. d. ryman et al., j. virol. 74:3366-3378, 2000). probing of the specific antiviral proteins important for ifn-mediat ...200818160435
synthetic heterovalent inhibitors targeting recognition e3 components of the n-end rule pathway.multivalent binding allows high selectivity and affinity in a ligand-protein interaction. the n-end rule pathway is a ubiquitin (ub)-dependent proteolytic system in which specific e3s, called n-recognins, mediate ubiquitylation through the recognition of types 1 and 2, destabilizing n-terminal residues of substrates. we recently identified a set of e3 ub ligases (named ubr1-ubr7) containing the 70-residue ubr box, and we demonstrated that ubr1, ubr2, ubr4, and ubr5 can bind to destabilizing n-te ...200818162545
envelope protein palmitoylations are crucial for murine coronavirus assembly.the coronavirus assembly process encloses a ribonucleoprotein genome into vesicles containing the lipid-embedded proteins s (spike), e (envelope), and m (membrane). this process depends on interactions with membranes that may involve palmitoylation, a common posttranslational lipidation of cysteine residues. to determine whether specific palmitoylations influence coronavirus assembly, we introduced plasmid dnas encoding mouse hepatitis coronavirus (mhv) s, e, m, and n (nucleocapsid) into 293t ce ...200818184706
experimental infection of aedes sollicitans and aedes taeniorhynchus with two chimeric sindbis/eastern equine encephalitis virus vaccine candidates.two chimeric vaccine candidates for eastern equine encephalitis virus (eeev) were developed by inserting the structural protein genes of either a north american (na) or south american (sa) eeev into a sindbis virus (sinv) backbone. to assess the effect of chimerization on mosquito infectivity, experimental infections of two potential north american bridge vectors of eeev, aedes sollicitans and ae. taeniorhynchus, were attempted. both species were susceptible to oral infection with all viruses af ...200818187790
autophagy in the pathogenesis of disease.autophagy is a lysosomal degradation pathway that is essential for survival, differentiation, development, and homeostasis. autophagy principally serves an adaptive role to protect organisms against diverse pathologies, including infections, cancer, neurodegeneration, aging, and heart disease. however, in certain experimental disease settings, the self-cannibalistic or, paradoxically, even the prosurvival functions of autophagy may be deleterious. this review summarizes recent advances in unders ...200818191218
intra-axonal translation and retrograde trafficking of creb promotes neuronal survival.during development of the nervous system, axons and growth cones contain mrnas such as beta-actin, cofilin and rhoa, which are locally translated in response to guidance cues. intra-axonal translation of these mrnas results in local morphological responses; however, other functions of intra-axonal mrna translation remain unknown. here, we show that axons of developing mammalian neurons contain mrna encoding the camp-responsive element (cre)-binding protein (creb). creb is translated within axons ...200818193038
the inflammatory cytokine, interleukin-1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitis.astrocytes remove glutamate from the synaptic cleft via specific transporters, and impaired glutamate reuptake may promote excitotoxic neuronal injury. in a model of viral encephalomyelitis caused by neuroadapted sindbis virus (nsv), mice develop acute paralysis and spinal motor neuron degeneration inhibited by the ampa receptor antagonist, nbqx. to investigate disrupted glutamate homeostasis in the spinal cord, expression of the main astroglial glutamate transporter, glt-1, was examined. glt-1 ...200818194440
yellow fever virus ns3 plays an essential role in virus assembly independent of its known enzymatic functions.in flaviviruses it has been proposed that there is a coupling between genome replication and virion assembly and that nonstructural proteins are involved in this process. it was previously reported that mutations in yellow fever virus (yfv) nonstructural protein ns2a blocked production of infectious virus and that this block could be released by a suppressor mutation in ns3. here, based on studies using a yfv replicon-based trans-packaging system as well as full-length yfv cdna, we report that m ...200818199634
targeted cell entry of lentiviral vectors.retargeting of lentiviral vector entry to cell types of interest is a key factor in improving the safety and efficacy of gene transfer. in this study we show that the retargetable envelope glycoproteins of measles virus (mv), namely, the hemagglutinin (h) responsible for receptor recognition and the fusion protein (f), can pseudotype human immunodeficiency virus 1 (hiv-1) vectors when their cytoplasmic tails are truncated. we then pseudotyped hiv-1 vectors with mv glycoproteins displaying on h e ...200818578012
activity-induced polo-like kinase 2 is required for homeostatic plasticity of hippocampal neurons during epileptiform activity.homeostatic plasticity mechanisms stabilize the activity of a neuron or neuronal circuit during prolonged periods of increased network activity and have been proposed to function in the prevention of epilepsy. how homeostatic plasticity is achieved at the molecular level during hyperactivity states in general, and during epileptiform activity in particular, is unclear. using organotypic hippocampal slice cultures as a model system, we found that the protein kinase polo-like kinase 2 (plk2) was i ...200818579731
alphavirus replicon particles acting as adjuvants promote cd8+ t cell responses to co-delivered antigen.alphavirus replicon particles induce strong antibody and cd8+ t cell responses to expressed antigens in numerous experimental systems. we have recently demonstrated that venezuelan equine encephalitis virus replicon particles (vrp) possess adjuvant activity for systemic and mucosal antibody responses. in this report, we demonstrate that vrp induced an increased and balanced serum igg subtype response to co-delivered antigen, with simultaneous induction of antigen-specific igg1 and igg2a antibodi ...200818582997
[isolation of influenza virus a (orthomyxoviridae, influenza a virus), dhori virus (orthomyxoviridae, thogotovirus), and newcastle's disease virus (paromyxoviridae, avulavirus) on the malyi zhemchuzhnyi island in the north-western area of the caspian sea].the paper presents the results of the 2003 and 2006 environmental virological monitoring surveys on the malyi zhemchuzhnyi island where a large breeding colony of sea gull (laridae) is located. in the past several years, expansion of cormorants (phalacrocorax carbo) has enhanced the intensity of populational interactions. the investigators isolated 13 strains of influenza a virus (orthomyxoviridae, influenza a virus) subtype h13n1 (from sea gulls (n = 4), cormorants (n = 9) 1 strain of dhori vir ...200818590134
targeting lentiviral vectors to antigen-specific immunoglobulins.gene transfer into b cells by lentivectors can provide an alternative approach to managing b lymphocyte malignancies and autoreactive b cell-mediated autoimmune diseases. these pathogenic b cell populations can be distinguished by their surface expression of monospecific immunoglobulin. development of a novel vector system to deliver genes to these specific b cells could improve the safety and efficacy of gene therapy. we have developed an efficient method to target lentivectors to monospecific ...200818590376
the dynamic envelope of a fusion class ii virus. e3 domain of glycoprotein e2 precursor in semliki forest virus provides a unique contact with the fusion protein e1.in alphaviruses, here represented by semliki forest virus, infection requires an acid-responsive spike configuration to facilitate membrane fusion. the creation of this relies on the chaperone function of glycoprotein e2 precursor (p62) and its maturation cleavage into the small external e3 and the membrane-anchored e2 glycoproteins. to reveal how the e3 domain of p62 exerts its control of spike functions, we determine the structure of a p62 cleavage-impaired mutant virus particle (sql) by elect ...200818596032
preferential cytolysis of peripheral memory cd4+ t cells by in vitro x4-tropic human immunodeficiency virus type 1 infection before the completion of reverse transcription.cd4+ t-cell depletion is the hallmark of aids pathogenesis. multiple mechanisms may contribute to the death of productively infected cd4+ t cells and innocent-bystander cells. in this study, we characterize a novel mechanism in which human immunodeficiency virus type 1 (hiv-1) infection preferentially depletes peripheral memory cd4+ t cells before the completion of reverse transcription. using a recombinant hiv-1 carrying the green fluorescent protein reporter gene, we demonstrate that memory cd ...200818596085
molecular defects caused by temperature-sensitive mutations in semliki forest virus nsp1.alphavirus replicase protein nsp1 has multiple functions during viral rna synthesis. it catalyzes methyltransferase and guanylyltransferase activities needed in viral mrna capping, attaches the viral replication complex to cytoplasmic membranes, and is required for minus-strand rna synthesis. two temperature-sensitive (ts) mutations in semliki forest virus (sfv) were previously identified within nsp1: ts10 (e529d) and ts14 (d119n). recombinant viruses containing these individual mutations reprod ...200818596091
survival of enveloped and non-enveloped viruses on surfaces compared with other micro-organisms and impact of suboptimal disinfectant exposure.survival of enveloped and non-enveloped viruses was compared with that of bacteria, yeasts and mycobacteria when dried on the surface of polyvinyl chloride test carriers in the presence or absence of an organic matrix. the efficacy of glutaraldehyde and accelerated hydrogen peroxide (ahp) disinfectants was evaluated. reovirus, a non-enveloped virus, persisted and had a rf of 2 after 30 days whereas enterococcus faecalis had an rf of 4 over the same time period. the other test organisms (sindbis ...200818602193
vaccinia virus e3 protein prevents the antiviral action of isg15.the ubiquitin-like modifier isg15 is one of the most predominant proteins induced by type i interferons (ifn). in this study, murine embryo fibroblast (mefs) and mice lacking the gene were used to demonstrate a novel role of isg15 as a host defense molecule against vaccinia virus (vacv) infection. in mefs, the growth of replication competent western reserve (wr) vacv strain was affected by the absence of isg15, but in addition, virus lacking e3 protein (vvdeltae3l) that is unable to grow in isg1 ...200818604270
the aedes aegypti toll pathway controls dengue virus infection.aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. to date, the features of insects' innate immune defenses against viruses have mainly been studied in the fruit fly drosophila melanogaster, which appears to utilize different immune pathways against different types of viruses, in addition to an rna interference-based defense system. we have used the recently released whole-genome s ...200818604274
nitrosylation of isg15 prevents the disulfide bond-mediated dimerization of isg15 and contributes to effective isgylation.the expression of the ubiquitin-like molecule isg15 (ucrp) and protein modification by isg15 (isgylation) are strongly activated by interferon, genotoxic stress, and pathogen infection, suggesting that isg15 plays an important role in innate immune responses. inducible nitric-oxide synthase (inos) is induced by the similar stimuli as isg15 and enhances the production of nitric oxide (no), a pleiotropic free radical with antipathogen activity. here, we report that cysteine residues (cys-76 and -1 ...200818606809
ubiquitination is required for effective replication of coxsackievirus b3.protein ubiquitination and/or degradation by the ubiquitin/proteasome system (ups) have been recognized as critical mechanisms in the regulation of numerous essential cellular functions. the importance of the ups in viral pathogenesis has become increasingly apparent. using murine cardiomyocytes, we have previously demonstrated that the ups plays a key role in the replication of coxsackievirus b3 (cvb3), an important human pathogen associated with various diseases. to further elucidate the under ...200818612413
activity of the small modified amino acid alpha-hydroxy glycineamide on in vitro and in vivo human immunodeficiency virus type 1 capsid assembly and infectivity.upon maturation of the human immunodeficiency virus type 1 (hiv-1) virion, proteolytic cleavage of the gag precursor protein by the viral protease is followed by morphological changes of the capsid protein p24, which will ultimately transform the virus core from an immature spherical to a mature conical structure. virion infectivity is critically dependent on the optimal semistability of the capsid cone structure. we have reported earlier that glycineamide (g-nh(2)), when added to the culture me ...200818644965
molecular engineering of viral gene delivery vehicles.viruses can be engineered to efficiently deliver exogenous genes, but their natural gene delivery properties often fail to meet human therapeutic needs. therefore, engineering viral vectors with new properties, including enhanced targeting abilities and resistance to immune responses, is a growing area of research. this review discusses protein engineering approaches to generate viral vectors with novel gene delivery capabilities. rational design of viral vectors has yielded successful advances ...200818647114
protein kinase a mediates activity-dependent kv4.2 channel trafficking.the a-type potassium channel subunit kv4.2 influences hippocampal function through regulation of dendritic excitability, and changes in kv4.2 surface expression alter synaptic plasticity. recent data from our laboratory demonstrate that egfp (enhanced green fluorescent protein)-tagged kv4.2 channels located in dendritic spines are internalized in an activity-dependent manner after synaptic stimulation and during chemically induced long-term potentiation. however, the molecular trigger for kv4.2 ...200818650329
effector cd4+ t-cell involvement in clearance of infectious herpes simplex virus type 1 from sensory ganglia and spinal cords.in primary infection, cd8(+) t cells are important for clearance of infectious herpes simplex virus (hsv) from sensory ganglia. in this study, evidence of cd4(+) t-cell-mediated clearance of infectious hsv type 1 (hsv-1) from neural tissues was also detected. in immunocompetent mice, hsv-specific cd4(+) t cells were present in sensory ganglia and spinal cords coincident with hsv-1 clearance from these sites and remained detectable at least 8 months postinfection. neural cd4(+) t cells isolated a ...200818667492
murine coronavirus mouse hepatitis virus is recognized by mda5 and induces type i interferon in brain macrophages/microglia.the coronavirus mouse hepatitis virus (mhv) induces a minimal type i interferon (ifn) response in several cell types in vitro despite the fact that the type i ifn response is important in protecting the mouse from infection in vivo. when infected with mhv, mice deficient in ifn-associated receptor expression (ifnar(-/-)) became moribund by 48 h postinfection. mhv also replicated to higher titers and exhibited a more broad tissue tropism in these mice, which lack a type i ifn response. interestin ...200818667505
kv4 accessory protein dppx (dpp6) is a critical regulator of membrane excitability in hippocampal ca1 pyramidal neurons.a-type k+ currents have unique kinetic and voltage-dependent properties that allow them to finely tune synaptic integration, action potential (ap) shape and firing patterns. in hippocampal ca1 pyramidal neurons, kv4 channels make up the majority of the somatodendritic a-type current. studies in heterologous expression systems have shown that kv4 channels interact with transmembrane dipeptidyl-peptidase-like proteins (dppls) to regulate the surface trafficking and biophysical properties of kv4 ch ...200818667548
ras signaling mechanisms underlying impaired glur1-dependent plasticity associated with fragile x syndrome.fragile x syndrome, caused by the loss of fmr1 gene function and loss of fragile x mental retardation protein (fmrp), is the most commonly inherited form of mental retardation. the syndrome is characterized by associative learning deficits, reduced risk of cancer, dendritic spine dysmorphogenesis, and facial dysmorphism. however, the molecular mechanism that links loss of function of fmr1 to the learning disability remains unclear. here, we report an examination of small gtpase ras signaling and ...200818667617
the capsid-coding region hairpin element (chp) is a critical determinant of dengue virus and west nile virus rna synthesis.dengue virus (denv) and west nile virus (wnv) are members of the flavivirus genus of positive-strand rna viruses. rna sequences and structures, primarily in the untranslated regions, have been shown to modulate flaviviral gene expression and genome replication. previously, we demonstrated that a structure in the denv coding region (chp) enhances translation start codon selection and is required for viral replication. here we further characterize the role of the chp in the denv life cycle. we dem ...200818676000
downregulation of protein disulfide isomerase in sepsis and its role in tumor necrosis factor-alpha release.protein disulfide isomerase (pdi) is an important factor for the protein modification step in the post-translational event. pdi plays an essential role in cell survival under various stress conditions. it has been reported that pdi can serve as a negative regulator of nuclear factor-kappa-b (nf-kappab) and that it can inhibit lipopolysaccharide (lps)-induced proinflammatory cytokine production in macrophages. thus, pdi may be an intracellular anti-inflammatory molecule. although we have previous ...200818680601
oncolytic vaccinia virus: from bedside to benchtop and back.the field of oncolytic viral therapy has undergone a major shift in focus in the last few years. less research has been directed at making incremental improvements in original vectors based mainly on strains of adenovirus and hsv; instead a variety of different viral strains have been suggested as potential backbones for future oncolytic viruses (including newcastle disease virus, reovirus, vesicular stomatitis virus, polio virus, retrovirus, sindbis virus, picornavirus, mumps and measles virus) ...200818683104
different types of nsp3-containing protein complexes in sindbis virus-infected cells.alphaviruses represent a serious public health threat and cause a wide variety of diseases, ranging from severe encephalitis, which can result in death or neurological sequelae, to mild infection, characterized by fever, skin rashes, and arthritis. in the infected cells, alphaviruses express only four nonstructural proteins, which function in the synthesis of virus-specific rnas and in modification of the intracellular environment. the results of our study suggest that sindbis virus (sinv) infec ...200818684830
the requirement of reactive oxygen intermediates for lymphocytic choriomeningitis virus binding and growth.multiple viruses induce reactive oxygen intermediate (roi) generation during infection that plays an important role in growth. we have examined the importance of roi during lymphocytic choriomeningitis virus (lcmv) infection of immortalized bhk-21 cells and murine peritoneal macrophages. within 15 min of virus addition, intracellular roi levels increased. to examine the contribution of roi to lcmv infection, cells were pretreated with antioxidant prior to virus addition. antioxidant treatment in ...200818691729
chimeric alphavirus vaccine candidates for chikungunya.chikungunya virus (chikv) is an emerging alphavirus that has caused major epidemics in india and islands off the east coast of africa since 2005. importations into europe and the americas, including one that led to epidemic transmission in italy during 2007, underscore the risk of endemic establishment elsewhere. because there is no licensed human vaccine, and an attenuated investigational new drug product developed by the u.s. army causes mild arthritis in some vaccinees, we developed chimeric ...200818692107
trafficking and intracellular atpase activity of human ecto-nucleotidase ntpdase3 and the effect of er-targeted ntpdase3 on protein folding.ecto-nucleoside triphosphate diphosphohydrolases, ntpdase1 (cd39) and ntpdase3, are integral plasma membrane proteins that hydrolyze extracellular nucleotides, thereby modulating the function of purinergic receptors. during processing in the secretory pathway, the active sites of ecto-nucleotidases are located in the lumen of vesicular compartments, thus raising the question whether the ecto-nucleotidases affect the atp-dependent processes in these compartments, including protein folding in the ...200818693757
pathogenic role of natural killer t and natural killer cells in acetaminophen-induced liver injury in mice is dependent on the presence of dimethyl sulfoxide.dimethyl sulfoxide (dmso) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. although dmso is generally thought of as being relatively inert, it can induce biological effects that are often overlooked. an example that highlights this potential problem is found in a recent report demonstrating a pathogenic role for natural killer t (nkt) and natural killer (nk) cells in acetaminophen-induced liver injury (aili) in c57bl/6 mice in which dmso was use ...200818712839
a duplex real-time reverse transcriptase polymerase chain reaction assay for the detection of st. louis encephalitis and eastern equine encephalitis viruses.a duplex taqman real-time reverse transcriptase polymerase chain reaction (pcr) assay was developed for the detection of st. louis encephalitis virus (slev) and eastern equine encephalitis virus (eeev), for use in human and vector surveillance. the respective targets selected for the assay were the conserved ns5 and e1 genes of the 2 viruses. because of the insufficient number of ns5 sequences from slev strains in the genbank database, we determined the sequence of an approximately 1-kb region f ...200818715737
regulation of postsynaptic rapgap spar by polo-like kinase 2 and the scfbeta-trcp ubiquitin ligase in hippocampal neurons.the ubiquitin-proteasome pathway (upp) regulates synaptic function, but little is known about specific upp targets and mechanisms in mammalian synapses. we report here that the scf(beta-trcp) complex, a multisubunit e3 ubiquitin ligase, targets the postsynaptic spine-associated rap gtpase activating protein (spar) for degradation in neurons. spar degradation by scf(beta-trcp) depended on the activity-inducible protein kinase polo-like kinase 2 (plk2). in the presence of plk2, spar physically ass ...200818723513
cre-dependent expression of multiple transgenes in isolated neurons of the adult forebrain.transgenic mice with mosaic, golgi-staining-like expression of enhanced green fluorescent protein (egfp) have been very useful in studying the dynamics of neuronal structure and function. in order to further investigate the molecular events regulating structural plasticity, it would be useful to express multiple proteins in the same sparse neurons, allowing co-expression of functional proteins or co-labeling of subcellular compartments with other fluorescent proteins. however, it has been diffic ...200818725976
[serological monitoring of arbovirus infections in the estuary of the kuban river (the 2006-2007 data)].solid-phase enzyme immunoassay, neutralization test, and the hemagglutination-inhibition test were used to study the sera from human beings (152 samples), agricultural animals (n = 77), hares (n = 3), and wild birds (n = 69), collected in 2006-2007 in the kuban river estuary (temryuk district, krasnodar territory). there were specific antibodies against viruses of west nile (wh), tick-borne encephalitis (tbe) (flaviviridae, flavivirus), sindbis (togaviridae, alphavirus), the antigenic complex of ...200818756814
sindbis virus vectors elicit hemagglutinin-specific humoral and cellular immune responses and offer a dose-sparing strategy for vaccination.we report here on the use of a sindbis virus-based dna-launch rna replicon vector (psin-ha) that expresses influenza hemagglutinin (ha) as an immunogen. immunization of mice with psin-ha generated anti-ha antibody and ctl responses and resulted in lower lung viral titers after influenza challenge when compared to controls. importantly, immunization with a low dose of psin-ha mediated significantly reduced lung viral titers following challenge at 43 weeks after the final immunization. in contrast ...200818761047
novel characteristics of the function and induction of murine p56 family proteins.the interferon-stimulated gene 56 (isg56) family is induced strongly in response to virus infection, interferons (ifns) and double-stranded rna (dsrna). in the mouse, this family comprises three members, isg56, isg54, and isg49, which are clustered on chromosome 19 and encode the corresponding proteins p56, p54, and p49. here, we report differential properties of these proteins and their distinct induction patterns in different cell types. all three murine proteins bound to the c-subunit of the ...200818768971
the cellular antiviral protein viperin is attenuated by proteasome-mediated protein degradation in japanese encephalitis virus-infected cells.viperin is identified as an antiviral protein induced by interferon (ifn), viral infections, and pathogen-associated molecules. in this study, we found that viperin is highly induced at the rna level by japanese encephalitis virus (jev) and sindbis virus (sin) and that viperin protein is degraded in jev-infected cells through a proteasome-dependent mechanism. promoter analysis revealed that sin induces viperin expression in an ifn-dependent manner but that jev by itself activates the viperin pro ...200818768981
eastern and venezuelan equine encephalitis viruses differ in their ability to infect dendritic cells and macrophages: impact of altered cell tropism on pathogenesis.eastern and venezuelan equine encephalitis viruses (eeev and veev, respectively) cause severe morbidity and mortality in equines and humans. like other mosquito-borne viruses, veev infects dendritic cells (dcs) and macrophages in lymphoid tissues, fueling a serum viremia and facilitating neuroinvasion. in contrast, eeev replicates poorly in lymphoid tissues, preferentially infecting osteoblasts. here, we demonstrate that infectivity of eeev for myeloid lineage cells including dcs and macrophages ...200818768986
the role of autophagy in mammalian development: cell makeover rather than cell death.autophagy is important for the degradation of bulk cytoplasm, long-lived proteins, and entire organelles. in lower eukaryotes, autophagy functions as a cell death mechanism or as a stress response during development. however, autophagy's significance in vertebrate development, and the role (if any) of vertebrate-specific factors in its regulation, remains unexplained. through careful analysis of the current autophagy gene mutant mouse models, we propose that in mammals, autophagy may be involved ...200818804433
semliki forest virus strongly reduces mosquito host defence signaling.the alphavirus genus within the togaviridae family contains several important mosquito-borne arboviruses. other than the antiviral activity of rnai, relatively little is known about alphavirus interactions with insect cell defences. here we show that semliki forest virus (sfv) infection of aedes albopictus-derived u4.4 mosquito cells reduces cellular gene expression. activation prior to sfv infection of pathways involving stat/imd, but not toll signaling reduced subsequent virus gene expression ...200818811601
isolation of human monoclonal antibodies by mammalian cell display.due to their low immunogenicity in patients, humanized or fully human mabs are becoming increasingly important for the treatment of a growing number of diseases, including cancer, infections, and immune disorders. here, we describe a technology allowing for the rapid isolation of fully human mabs. in contrast to previously described methods, b cells specific for an antigen of interest are directly isolated from peripheral blood mononuclear cells (pbmc) of human donors. recombinant, antigen-speci ...200818812621
light-induced rescue of breathing after spinal cord injury.paralysis is a major consequence of spinal cord injury (sci). after cervical sci, respiratory deficits can result through interruption of descending presynaptic inputs to respiratory motor neurons in the spinal cord. expression of channelrhodopsin-2 (chr2) and photostimulation in neurons affects neuronal excitability and produces action potentials without any kind of presynaptic inputs. we hypothesized that after transducing spinal neurons in and around the phrenic motor pool to express chr2, ph ...200819005051
a critical role of a cellular membrane traffic protein in poliovirus rna replication.replication of many rna viruses is accompanied by extensive remodeling of intracellular membranes. in poliovirus-infected cells, er and golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral rna synthesis. virus replication is inhibited by brefeldin a (bfa), implicating some components(s) of the cellular secretory pathway in virus growth. formation of characteristic vesicles induced by expression of viral proteins was not inhibited by bfa, but they were functi ...200819023417
rapid, bidirectional remodeling of synaptic nmda receptor subunit composition by a-type k+ channel activity in hippocampal ca1 pyramidal neurons.the transient, a-type k+ current (ia) controls the excitability of ca1 pyramidal neuron dendrites by regulating the back-propagation of action potentials and by shaping synaptic input. dendritic a-type k+ channels are targeted for modulation during long-term potentiation (ltp) and we have recently shown that activity-dependent internalization of the a-type channel subunit kv4.2 enhances synaptic currents. however, the effect of changes in ia on the ability to induce subsequent synaptic plasticit ...200819038222
yellow fever vaccine induces integrated multilineage and polyfunctional immune responses.correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. this impedes the development of novel vaccines to incurable diseases such as hiv and cancer. in this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (yf) vaccine 17d (yf17d) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. we show that immunization with yf17d leads to an integrated immune r ...200819047440
alphavirus-derived small rnas modulate pathogenesis in disease vector mosquitoes.mosquito-borne viruses cause significant levels of morbidity and mortality in humans and domesticated animals. maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. although the vertebrate infection is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosq ...200819047642
west nile virus-specific cd4 t cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protection.cd4 t cells have been shown to be necessary for the prevention of encephalitis during west nile virus (wnv) infection. however, the mechanisms used by ag-specific cd4 t cells to protect mice from wnv encephalitis remain incompletely understood. contrary to the belief that cd4 t cells are protective because they merely maintain the cd8 t cell response and improve ab production, in this study we provide evidence for the direct antiviral activity of cd4 t cells that functions to protect the host fr ...200819050276
independent regulation of reovirus membrane penetration and apoptosis by the mu1 phi domain.apoptosis plays an important role in the pathogenesis of reovirus encephalitis. reovirus outer-capsid protein mu1, which functions to penetrate host cell membranes during viral entry, is the primary regulator of apoptosis following reovirus infection. ectopic expression of full-length and truncated forms of mu1 indicates that the mu1 phi domain is sufficient to elicit a cell death response. to evaluate the contribution of the mu1 phi domain to the induction of apoptosis following reovirus infect ...200819112493
analysis of the survival of venezuelan equine encephalomyelitis virus and possible viral simulants in liquid suspensions.to compare the inactivation rate of venezuelan equine encephalomyelitis (vee) virus in liquids to that of sindbis virus (sv, another alphavirus) and to a bacteriophage (ms2) generally used as a viral simulant in the development of countermeasures in biodefense.200819146486
identification and analysis of putative promoter motifs in flavivirus genome.the genus flavivirus comprises medically significant pathogenic virus; causing several infections in humans worldwide. flavivirus genomes are 10-11 kb approximately and encode both structural and non structural region. the non structural region plays fundamental role in the stability, regulation and cell cycle of virus. the complete genomes of 26 flavivirus were used for identification of promoter motifs through in silico approaches. the promoter sequences were encoded in merely 16 viruses and 1 ...200819238240
the autophagy effector beclin 1: a novel bh3-only protein.bh3 domains were originally discovered in the context of apoptosis regulators and they mediate binding of proapoptotic bcl-2 family members to antiapoptotic bcl-2 family members. yet, recent studies indicate that bh3 domains do not function uniquely in apoptosis regulation; they also function in the regulation of another critical pathway involved in cellular and tissue homeostasis called autophagy. antiapoptotic bcl-2 homologs downregulate autophagy through interactions with the essential autoph ...200819641499
complement and its role in protection and pathogenesis of flavivirus infections.the complement system is a family of serum and cell surface proteins that recognize pathogen-associated molecular patterns, altered-self ligands, and immune complexes. activation of the complement cascade triggers several antiviral functions including pathogen opsonization and/or lysis, and priming of adaptive immune responses. in this review, we will examine the role of complement activation in protection and/or pathogenesis against infection by flaviviruses, with an emphasis on experiments wit ...200819388173
retrospective survey of chikungunya disease in réunion island hospital staff.réunion island (indian ocean) has been suffering from its first known chikungunya virus (chikv) epidemic since february 2005. to achieve a better understanding of the disease, a questionnaire was drawn up for hospital staff members and their household. chikv infected about one-third of the studied population, the proportion increasing with age and being higher in women. presence of a garden was associated with chikv infection. the geographical distribution of cases was concordant with insect vec ...200817433130
structural and biochemical bases for the inhibition of autophagy and apoptosis by viral bcl-2 of murine gamma-herpesvirus 68.all gammaherpesviruses express homologues of antiapoptotic b-cell lymphoma-2 (bcl-2) to counter the clearance of infected cells by host antiviral defense machineries. to gain insights into the action mechanisms of these viral bcl-2 proteins, we carried out structural and biochemical analyses on the interactions of m11, a viral bcl-2 of murine gamma-herpesvirus 68, with a fragment of proautophagic beclin1 and bcl-2 homology 3 (bh3) domain-containing peptides derived from an array of proapoptotic ...200818248095
annotation and expression profiling of apoptosis-related genes in the yellow fever mosquito, aedes aegypti.apoptosis has been extensively studied in drosophila by both biochemical and genetic approaches, but there is a lack of knowledge about the mechanisms of apoptosis regulation in other insects. in mosquitoes, apoptosis occurs during plasmodium and arbovirus infection in the midgut, suggesting that apoptosis plays a role in mosquito innate immunity. we searched the aedes aegypti genome for apoptosis-related genes using drosophila and anopheles gambiae protein sequences as queries. in this study we ...200818252247
venezuelan equine encephalitis virus capsid protein inhibits nuclear import in mammalian but not in mosquito cells.venezuelan equine encephalitis virus (veev) represents a continuous public health threat in the united states. it has the ability to cause fatal disease in humans and in horses and other domestic animals. we recently demonstrated that replicating veev interferes with cellular transcription and uses this phenomenon as a means of downregulating a cellular antiviral response. veev capsid protein was found to play a critical role in this process, and its approximately 35-amino-acid-long peptide, fus ...200818256144
sindbis virus infection in resident birds, migratory birds, and humans, finland.sindbis virus (sinv), a mosquito-borne virus that causes rash and arthritis, has been causing outbreaks in humans every seventh year in northern europe. to gain a better understanding of sinv epidemiology in finland, we searched for sinv antibodies in 621 resident grouse, whose population declines have coincided with human sinv outbreaks, and in 836 migratory birds. we used hemagglutination-inhibition and neutralization tests for the bird samples and enzyme immunoassays and hemagglutination-inhi ...200818258075
killing of macrophages by anthrax lethal toxin: involvement of the n-end rule pathway.macrophages from certain inbred mouse strains are rapidly killed (< 90 min) by anthrax lethal toxin (lt). lt cleaves cytoplasmic mek proteins at 20 min and induces caspase-1 activation in sensitive macrophages at 50-60 min, but the mechanism of lt-induced death is unknown. proteasome inhibitors block lt-mediated caspase-1 activation and can protect against cell death, indicating that the degradation of at least one cellular protein is required for lt-mediated cell death. proteins can be degraded ...200818266992
the 67 kda laminin receptor: structure, function and role in disease.the 67lr (67 kda laminin receptor) is a cell-surface receptor with high affinity for its primary ligand. its role as a laminin receptor makes it an important molecule both in cell adhesion to the basement membrane and in signalling transduction following this binding event. the protein also plays critical roles in the metastasis of tumour cells. isolation of the protein from either normal or cancerous cells results in a product with an approx. molecular mass of 67 kda. this protein is believed t ...200818269348
mutations in the nuclear localization signal of nsp2 influencing rna synthesis, protein expression and cytotoxicity of semliki forest virus.the cytotoxicity of semliki forest virus (sfv) infection is caused partly by the non-structural protein nsp2, an essential component of the sfv replicase complex. due to the presence of a nuclear localization signal (nls), nsp2 also localizes in the nucleus of infected cells. the present study analysed recombinant sfv replicons and genomes with various deletions or substitutions in the nls, or with a proline-to-glycine mutation at position 718 of nsp2 (p718g). deletion of one or two arginine res ...200818272758
translational control of the innate immune response through irf-7.transcriptional activation of cytokines, such as type-i interferons (interferon (ifn)-alpha and ifn-beta), constitutes the first line of antiviral defence. here we show that translational control is critical for induction of type-i ifn production. in mouse embryonic fibroblasts lacking the translational repressors 4e-bp1 and 4e-bp2, the threshold for eliciting type-i ifn production is lowered. consequently, replication of encephalomyocarditis virus, vesicular stomatitis virus, influenza virus an ...200818272964
increased virus replication in mammalian cells by blocking intracellular innate defense responses.the mammalian innate immune system senses viral infection by recognizing viral signatures and activates potent antiviral responses. besides the interferon (ifn) response, there is accumulating evidence that rna silencing or rna interference (rnai) serves as an antiviral mechanism in mammalian cells. mammalian viruses encode ifn antagonists to counteract the ifn response in infected cells. a number of ifn antagonists are also capable of blocking rnai in infected cells and therefore serve as rna-s ...200818273055
a mouse model for chikungunya: young age and inefficient type-i interferon signaling are risk factors for severe disease.chikungunya virus (chikv) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the indian ocean region and india. infection from chikv typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. cases of severe chikv infection involving the central nervous system (cns) have recently been described in neonates as well as in adults with underlying conditions. the pathophysiology of chikv infection and the basis for disease severi ...200818282093
isg15 inhibits nedd4 ubiquitin e3 activity and enhances the innate antiviral response.interferons regulate diverse immune functions through the transcriptional activation of hundreds of genes involved in anti-viral responses. the interferon-inducible ubiquitin-like protein isg15 is expressed in cells in response to a variety of stress conditions like viral or bacterial infection and is present in its free form or is conjugated to cellular proteins. in addition, protein ubiquitination plays a regulatory role in the immune system. many viruses modulate the ubiquitin (ub) pathway to ...200818287095
dose-dependent protection against or exacerbation of disease by a polylactide glycolide microparticle-adsorbed, alphavirus-based measles virus dna vaccine in rhesus macaques.measles remains an important cause of vaccine-preventable child mortality. development of a low-cost, heat-stable vaccine for infants under the age of 6 months could improve measles control by facilitating delivery at the time of other vaccines and by closing a window of susceptibility prior to immunization at 9 months of age. dna vaccines hold promise for development, but achieving protective levels of antibody has been difficult and there is an incomplete understanding of protective immunity. ...200818287579
a luciferase-based screening method for inhibitors of alphavirus replication applied to nucleoside analogues.several members of the widespread alphavirus group are pathogenic, but no therapy is available to treat these rna virus infections. we report here a quantitative assay to screen for inhibitors of semliki forest virus (sfv) replication, and demonstrate the effects of 29 nucleosides on sfv and sindbis virus replication. the anti-sfv assay developed is based on a sfv strain containing renilla luciferase inserted after the nsp3 coding region, yielding a marker virus in which the luciferase is cleave ...200818294708
protection from fatal viral encephalomyelitis: ampa receptor antagonists have a direct effect on the inflammatory response to infection.neuronal cell death during fatal acute viral encephalomyelitis can result from damage caused by virus replication, glutamate excitotoxicity, and the immune response. a neurovirulent strain of the alphavirus sindbis virus (nsv) causes fatal encephalomyelitis associated with motor neuron death in adult c57bl/6 mice that can be prevented by treatment with the prototypic noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (ampa) glutamate receptor antagonist gyki 52466 [nargi-ai ...200818296635
engineered lentivector targeting of dendritic cells for in vivo immunization.we report a method of inducing antigen production in dendritic cells by in vivo targeting with lentiviral vectors that specifically bind to the dendritic cell-surface protein dc-sign. to target dendritic cells, we enveloped the lentivector with a viral glycoprotein from sindbis virus engineered to be dc-sign-specific. in vitro, this lentivector specifically transduced dendritic cells and induced dendritic cell maturation. a high frequency (up to 12%) of ovalbumin (ova)-specific cd8(+) t cells an ...200818297056
inhibition of arp2/3-mediated actin polymerization by pick1 regulates neuronal morphology and ampa receptor endocytosis.the dynamic regulation of actin polymerization plays crucial roles in cell morphology and endocytosis. the mechanistic details of these processes and the proteins involved are not fully understood, especially in neurons. pick1 is a pdz-bar-domain protein involved in regulated ampa receptor (ampar) endocytosis in neurons. here, we demonstrate that pick1 binds filamentous (f)-actin and the actin-nucleating arp2/3 complex, and potently inhibits arp2/3-mediated actin polymerization. rna interference ...200818297063
proteasome inhibitor-induced apoptosis is mediated by positive feedback amplification of pkcdelta proteolytic activation and mitochondrial translocation.emerging evidence implicates impaired protein degradation by the ubiquitin proteasome system (ups) in parkinson's disease; however cellular mechanisms underlying dopaminergic degeneration during proteasomal dysfunction are yet to be characterized. in the present study, we identified that the novel pkc isoform pkcdelta plays a central role in mediating apoptotic cell death following ups dysfunction in dopaminergic neuronal cells. inhibition of proteasome function by mg-132 in dopaminergic neurona ...200818298651
rubella virus capsid protein interacts with poly(a)-binding protein and inhibits translation.during virus assembly, the capsid proteins of rna viruses bind to genomic rna to form nucleocapsids. however, it is now evident that capsid proteins have additional functions that are unrelated to nucleocapsid formation. specifically, their interactions with cellular proteins may influence signaling pathways or other events that affect virus replication. here we report that the rubella virus (rv) capsid protein binds to poly(a)-binding protein (pabp), a host cell protein that enhances translatio ...200818305028
role of sindbis virus capsid protein region ii in nucleocapsid core assembly and encapsidation of genomic rna.sindbis virus is an enveloped positive-sense rna virus in the alphavirus genus. the nucleocapsid core contains the genomic rna surrounded by 240 copies of a single capsid protein. the capsid protein is multifunctional, and its roles include acting as a protease, controlling the specificity of rna that is encapsidated into nucleocapsid cores, and interacting with viral glycoproteins to promote the budding of mature virus and the release of the genomic rna into the newly infected cell. the region ...200818305029
coronavirus infection modulates the unfolded protein response and mediates sustained translational repression.during coronavirus replication, viral proteins induce the formation of endoplasmic reticulum (er)-derived double-membrane vesicles for rna synthesis, and viral structural proteins assemble virions at the er-golgi intermediate compartment. we hypothesized that the association and intense utilization of the er during viral replication would induce the cellular unfolded protein response (upr), a signal transduction cascade that acts to modulate translation, membrane biosynthesis, and the levels of ...200818305036
formation of the arterivirus replication/transcription complex: a key role for nonstructural protein 3 in the remodeling of intracellular membranes.the replication/transcription complex of the arterivirus equine arteritis virus (eav) is associated with paired membranes and/or double-membrane vesicles (dmvs) that are thought to originate from the endoplasmic reticulum. previously, coexpression of two putative transmembrane nonstructural proteins (nsp2 and nsp3) was found to suffice to induce these remarkable membrane structures, which are typical of arterivirus infection. here, site-directed mutagenesis was used to investigate the role of ns ...200818305048
severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type i interferon, in infected cells.the severe acute respiratory syndrome coronavirus (sars-cov) nsp1 protein has unique biological functions that have not been described in the viral proteins of any rna viruses; expressed sars-cov nsp1 protein has been found to suppress host gene expression by promoting host mrna degradation and inhibiting translation. we generated an nsp1 mutant (nsp1-mt) that neither promoted host mrna degradation nor suppressed host protein synthesis in expressing cells. both a sars-cov mutant virus, encoding ...200818305050
isg15 inhibits ebola vp40 vlp budding in an l-domain-dependent manner by blocking nedd4 ligase activity.ebola virus budding is mediated by the vp40 matrix protein. vp40 can bud from mammalian cells independent of other viral proteins, and efficient release of vp40 virus-like particles (vlps) requires interactions with host proteins such as tsg101 and nedd4, an e3 ubiquitin ligase. ubiquitin itself is thought to be exploited by ebola virus to facilitate efficient virus egress. disruption of vp40 function and thus virus budding remains an attractive target for the development of novel antiviral ther ...200818305167
orthomyxo-, paramyxo- and flavivirus infections in wild waterfowl in finland.screening wild birds for viral pathogens has become increasingly important. we tested a screening approach based on blood and cloacal and tracheal swabs collected by hunters to study the prevalence of influenza a, paramyxo-, flavi-, and alphaviruses in finnish wild waterfowl, which has been previously unknown. we studied 310 blood samples and 115 mixed tracheal and cloacal swabs collected from hunted waterfowl in 2006. samples were screened by rt-pcr and serologically by hemagglutination inhibit ...200818307758
nlrx1: friend or foe? 200818311173
c3h/hen mouse model for the evaluation of antiviral agents for the treatment of venezuelan equine encephalitis virus infection.the tc-83 vaccine strain of venezuelan equine encephalitis virus (veev) causes encephalitis and death in c3h/hen mice infected by intranasal (i.n.) instillation. since tc-83 is exempt as a select agent, this mouse model was used in the evaluation of antiviral therapies. virus titers in the brains of infected mice peaked on 4 dpi and persisted at high levels until death at 9.4+/-0.5 dpi. mouse brains appeared histologically normal on 2 dpi, but developed meningoencephalitis, neuropil vacuolation, ...200818313150
the interferon-induced protein bst-2 restricts hiv-1 release and is downregulated from the cell surface by the viral vpu protein.the hiv-1 accessory protein vpu counteracts a host factor that restricts virion release from infected cells. here we show that the interferon-induced cellular protein bst-2/hm1.24/cd317 is such a factor. bst-2 is downregulated from the cell surface by vpu, and bst-2 is specifically expressed in cells that support the vpu phenotype. exogenous expression of bst-2 inhibits hiv-1 virion release, while suppression of bst-2 relieves the requirement for vpu. downregulation of bst-2 requires both the tr ...200818342597
the enhancement of arbovirus transmission and disease by mosquito saliva is associated with modulation of the host immune response.arthropod-borne (arbo-) viruses have emerged as a major human health concern. viruses transmitted by mosquitoes are the cause of the most serious and widespread arbovirus diseases worldwide and are ubiquitous in both feral and urban settings. arboviruses, including dengue and west nile virus, are injected into vertebrates within mosquito saliva during mosquito feeding. mosquito saliva contains anti-haemostatic, anti-inflammatory and immunomodulatory molecules that facilitate the acquisition of a ...200818342898
experimental reovirus-induced acute flaccid paralysis and spinal motor neuron cell death.acute flaccid paralysis (afp) describes the loss of motor function in 1 or more limbs commonly associated with viral infection and destruction of motor neurons in the anterior horns of the spinal cord. therapy is limited, and the development of effective treatments is hampered by a lack of experimental models. reovirus infection of neonatal mice provides a model for the study of cns viral infection pathogenesis. injection of the reovirus serot type 3 strains abney (t3a) or dearing (t3d) into the ...200818344914
therapeutic human papillomavirus vaccines: current clinical trials and future directions.cervical cancer is the second largest cause of cancer deaths in women worldwide. it is now evident that persistent infection with high-risk human papillomavirus (hpv) is necessary for the development and maintenance of cervical cancer. thus, effective vaccination against hpv represents an opportunity to restrain cervical cancer and other important cancers. the fda recently approved the hpv vaccine gardasil for the preventive control of hpv, using hpv virus-like particles (vlp) to generate neutra ...200818352847
structural and nonstructural protein genome regions of eastern equine encephalitis virus are determinants of interferon sensitivity and murine virulence.eastern equine encephalitis virus (eeev) causes sporadic epidemics of human and equine disease in north america, but south american strains have seldom been associated with human neurologic disease or mortality, despite serological evidence of infection. in mice, most north american and south american strains of eeev produce neurologic disease that resembles that associated with human and equine infections. we identified a south american strain that is unable to replicate efficiently in the brai ...200818353963
infectivity studies of influenza virus hemagglutinin receptor binding site mutants in mice.the replicative properties of influenza virus hemagglutinin (ha) mutants with altered receptor binding characteristics were analyzed following intranasal inoculation of mice. among the mutants examined was a virus containing a y98f substitution at a conserved position in the receptor binding site that leads to a 20-fold reduction in binding. this mutant can replicate as well as wild-type (wt) virus in mdck cells and in embryonated chicken eggs but is highly attenuated in mice, exhibiting titers ...200818353965
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