Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
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| inhibition of anti-hiv microrna expression: a mechanism for opioid-mediated enhancement of hiv infection of monocytes. | several micro rnas (mirnas) have the ability to inhibit hiv replication in target cells. thus, we investigated the impact of opioids (morphine and heroin), widely abused drugs among people infected with hiv, on the expression of cellular anti-hiv mirnas in monocytes. we found that morphine-treated monocytes expressed lower levels of cellular anti-hiv mirnas than untreated cells. in addition, morphine treatment of monocytes compromised type i interferon (ifn)-induced anti-hiv mirna expression. th ... | 2010 | 21224041 |
| interferon-stimulated gene 15 and the protein isgylation system. | interferon-stimulated gene 15 (isg15) is one of the most upregulated genes upon type i interferon treatment or pathogen infection. its 17 kda protein product, isg15, was the first ubiquitin-like modifier identified, and is similar to a ubiquitin linear dimer. as isg15 modifies proteins in a similar manner to ubiquitylation, protein conjugation by isg15 is termed isgylation. some of the primary enzymes that promote isgylation are also involved in ubiquitin conjugation. the process to remove isg1 ... | 2010 | 21190487 |
| antiviral rna interference responses induced by semliki forest virus infection of mosquito cells: characterization, origin, and frequency-dependent functions of virus-derived small interfering rnas. | rna interference (rnai) is an important mosquito defense mechanism against arbovirus infection. in this paper we study the processes underlying antiviral rnai in aedes albopictus-derived u4.4 mosquito cells infected with semliki forest virus (sfv) (togaviridae; alphavirus). the production of virus-derived small interfering rnas (virnas) from viral double-stranded rna (dsrna) is a key event in this host response. dsrna could be formed by rna replication intermediates, by secondary structures in r ... | 2010 | 21191029 |
| neurogranin phosphorylation fine-tunes long-term potentiation. | learning-related potentiation of synaptic strength at cornu ammonis subfield 1 (ca1) hippocampal excitatory synapses is dependent on neuronal activity and the activation of glutamate receptors. however, molecular mechanisms that regulate and fine-tune the expression of long-term potentiation (ltp) are not well understood. recently it has been indicated that neurogranin (ng), a neuron-specific, postsynaptic protein that is phosphorylated by protein kinase c, potentiates synaptic transmission in a ... | 2010 | 21198977 |
| analyses of selex-derived zap-binding rna aptamers suggest that the binding specificity is determined by both structure and sequence of the rna. | the zinc-finger antiviral protein (zap) is a host factor that specifically inhibits the replication of certain viruses, including murine leukemia virus, sindbis virus and ebola virus, by targeting the viral mrnas for degradation. zap directly binds to the target viral mrna and recruits the cellular rna degradation machinery to degrade the rna. no significant sequence similarity or obvious common motifs have been found in the so far identified target viral mrnas. the minimum length of the target ... | 2010 | 21203916 |
| interferon-stimulated gene isg12b2 is localized to the inner mitochondrial membrane and mediates virus-induced cell death. | interferons (ifns) are crucial for host defence against viruses. many ifn-stimulated genes (isgs) induced by viral infection exert antiviral effects. microarray analysis of gene expression induced in liver tissues of mice on dengue virus (denv) infection has led to identification of the isg gene isg12b2. isg12b2 is also dramatically induced on denv infection of hepa 1-6 cells (mouse hepatoma cell line). here, we performed biochemical and functional analyses of isg12b2. we demonstrate that isg12b ... | 2010 | 21151029 |
| virus assembly, allostery and antivirals. | assembly of virus capsids and surface proteins must be regulated to ensure that the resulting complex is an infectious virion. in this review, we examine assembly of virus capsids, focusing on hepatitis b virus and bacteriophage ms2, and formation of glycoproteins in the alphaviruses. these systems are structurally and biochemically well-characterized and are simplest-case paradigms of self-assembly. published data suggest that capsid and glycoprotein assembly is subject to allosteric regulation ... | 2010 | 21163649 |
| alphavirus transducing system: tools for visualizing infection in mosquito vectors. | alphavirus transducing systems (atss) are important tools for expressing genes of interest (goi) during infection. atss are derived from cdna clones of mosquito-borne rna viruses (genus alphavirus; family togaviridae). the alphavirus genus contains about 30 different mosquito-borne virus species. alphaviruses are enveloped viruses and contain single-stranded rna genomes (~11.7 kb). alphaviruses transcribe a subgenomic mrna that encodes the structural proteins of the virus required for encapsidat ... | 2010 | 21178952 |
| iota-carrageenan is a potent inhibitor of influenza a virus infection. | the 2009 flu pandemic and the appearance of oseltamivir-resistant h1n1 influenza strains highlight the need for treatment alternatives. one such option is the creation of a protective physical barrier in the nasal cavity. in vitro tests demonstrated that iota-carrageenan is a potent inhibitor of influenza a virus infection, most importantly also of pandemic h1n1/2009 in vitro. consequently, we tested a commercially available nasal spray containing iota-carrageenan in an influenza a mouse infecti ... | 2010 | 21179403 |
| blood feeding position increases success of recalcitrant mosquitoes. | abstract aedes aegypti and aedes albopictus are competent natural and laboratory vectors for numerous arthropod-borne viruses (arboviruses), many of which pose global public health concerns. efficiently imbibing a blood meal from an artificial membrane feeder, ae. aegypti is an easy feeder: ∼96% success. alternatively, ae. albopictus is known to be a difficult feeder imbibing poorly: ∼20% success. adult female mosquitoes were grouped in cohorts of 50, proffered a bovine blood meal, and challenge ... | 2010 | 21142951 |
| the costs of dominance: testosterone, cortisol and intestinal parasites in wild male chimpanzees. | abstract: | 2010 | 21143892 |
| formation of antiviral cytoplasmic granules during orthopoxvirus infection. | vaccinia virus (vv) mutants lacking the double-stranded rna (dsrna)-binding e3l protein (δe3l mutant vv) show restricted replication in most cell types, as dsrna produced by vv activates protein kinase r (pkr), leading to eif2α phosphorylation and impaired translation initiation. here we show that cells infected with δe3l mutant vv assemble cytoplasmic granular structures which surround the vv replication factories at an early stage of the nonproductive infection. these structures contain the st ... | 2010 | 21147913 |
| activity-dependent ubiquitination of glua1 mediates a distinct ampa receptor endocytosis and sorting pathway. | the accurate trafficking of ampa receptors (ampars) to and from the synapse is a critical component of learning and memory in the brain, whereas dysfunction of ampar trafficking is hypothesized to be an underlying mechanism of alzheimer's disease. previous work has shown that ubiquitination of integral membrane proteins is a common posttranslational modification used to mediate endocytosis and endocytic sorting of surface proteins in eukaryotic cells. here we report that mammalian ampars become ... | 2010 | 21148011 |
| proteomic analysis reveals virus-specific hsp25 modulation in cardiac myocytes. | viruses frequently infect the heart but clinical myocarditis is rare, suggesting that the cardiac antiviral response is uniquely effective. indeed, the type i interferon (ifn) response is cardiac cell-type specific and provides one integrated network of protection for the heart. here, a proteomic approach was used to identify additional proteins that may be involved in the cardiac antiviral response. reovirus-induced murine myocarditis reflects direct viral damage to cardiac cells and offers an ... | 2010 | 20196617 |
| immunotherapy for cervical cancer: research status and clinical potential. | the high-risk types of human papillomavirus (hpv) have been found to be associated with most cervical cancers and play an essential role in the pathogenesis of the disease. despite recent advances in preventive hpv vaccine development, such preventive vaccines are unlikely to reduce the prevalence of hpv infections within the next few years, due to their cost and limited availability in developing countries. furthermore, preventive hpv vaccines may not be capable of treating established hpv infe ... | 2010 | 20199126 |
| the vpu protein: new concepts in virus release and cd4 down-modulation. | human immunodeficiency virus type 1 (hiv-1) and several simian immunodeficiency viruses (siv) encode for a transmembrane protein known as vpu (viral protein u). while one of the smallest of the hiv-1 proteins, it has two important functions within virus-infected cells. the first of these functions is the down-regulation of the cd4 receptor to prevent its interaction with the hiv-1 envelope glycoprotein. vpu interacts with the cd4 receptor in the rough endoplasmic reticulum (rer), resulting in it ... | 2010 | 20201792 |
| translation control by protein kinase r restricts minute virus of mice infection: role in parvovirus oncolysis. | the relevance of translational control in the gene expression and oncotropism of the autonomous parvoviruses was investigated with mvmp, the prototype strain of minute virus of mice (mvm), infecting normal and transformed rodent and human cells of different tissue origins. mouse embryo fibroblasts (mefs) and nih 3t3 fibroblasts were resistant to mvmp infection, but 3t3 fibroblasts derived from double-stranded rna (dsrna)-dependent protein kinase r (pkr) knockout mice (pkr(o/o)) behaved in a mann ... | 2010 | 20219905 |
| the structure of sindbis virus produced from vertebrate and invertebrate hosts as determined by small-angle neutron scattering. | the complex natural cycle of vectored viruses that transition between host species, such as between insects and mammals, makes understanding the full life cycle of the virus an incredibly complex problem. sindbis virus, an arbovirus and prototypic alphavirus having an inner protein shell and an outer glycoprotein coat separated by a lipid membrane, is one example of a vectored virus that transitions between vertebrate and insect hosts. while evidence of host-specific differences in sindbis virus ... | 2010 | 20219936 |
| species-specific antagonism of host isgylation by the influenza b virus ns1 protein. | interferon-stimulated expression and conjugation of the ubiquitin-like modifier isg15 restricts replication of several viruses. here, we established complete e1-activating, e2-conjugating, and e3 ligase-dependent expression systems for assaying both human and mouse isgylation. we confirm that human herc5, but not human herc6, has isg15 e3 ligase activity and identify mouse herc6 as a bona fide isg15 e3 ligase. furthermore, we demonstrate that influenza b virus ns1 protein potently antagonizes hu ... | 2010 | 20219937 |
| antiviral activities of isg20 in positive-strand rna virus infections. | isg20 is an interferon-inducible 3'-5' exonuclease that inhibits replication of several human and animal rna viruses. however, the specificities of isg20's antiviral action remain poorly defined. here we determine the impact of ectopic expression of isg20 on replication of several positive-strand rna viruses from distinct viral families. isg20 inhibited infections by cell culture-derived hepatitis c virus (hcv) and a pestivirus, bovine viral diarrhea virus and a picornavirus, hepatitis a virus. ... | 2010 | 21036379 |
| structure-guided identification of a laminin binding site on the laminin receptor precursor. | the 37/ 67-kda human laminin receptor (lamr) is a cell surface receptor for laminin, prion protein, and a variety of viruses. because of its wide range of ligands, lamr plays a role in numerous pathologies. lamr overexpression correlates with a highly invasive cell phenotype and increased metastatic ability, mediated by interactions between lamr and laminin. in addition, the specific targeting of lamr with small interfering rnas, blocking antibodies, and sindbis viral vectors confers anti-tumor ... | 2010 | 21040730 |
| host alternation of chikungunya virus increases fitness while restricting population diversity and adaptability to novel selective pressures. | the mechanisms by which rna arboviruses, including chikungunya virus (chikv), evolve and maintain the ability to infect vertebrate and invertebrate hosts are poorly understood. to understand how host specificity shapes arbovirus populations, we studied chikv populations passaged alternately between invertebrate and vertebrate cells (invertebrate ↔ vertebrate) to simulate natural alternation and contrasted the results with those for populations that were artificially released from cycling by pass ... | 2010 | 21047966 |
| comparison of dengue virus type 2-specific small rnas from rna interference-competent and -incompetent mosquito cells. | the exogenous rna interference (rnai) pathway is an important antiviral defense against arboviruses in mosquitoes, and virus-specific small interfering (si)rnas are key components of this pathway. understanding the biogenesis of sirnas in mosquitoes could have important ramifications in using rnai to control arbovirus transmission. using deep sequencing technology, we characterized dengue virus type 2 (denv2)-specific small rnas produced during infection of aedes aegypti mosquitoes and a. aegypt ... | 2010 | 21049014 |
| c6/36 aedes albopictus cells have a dysfunctional antiviral rna interference response. | mosquitoes rely on rna interference (rnai) as their primary defense against viral infections. to this end, the combination of rnai and invertebrate cell culture systems has become an invaluable tool in studying virus-vector interactions. nevertheless, a recent study failed to detect an active rnai response to west nile virus (wnv) infection in c6/36 (aedes albopictus) cells, a mosquito cell line frequently used to study arthropod-borne viruses (arboviruses). therefore, we sought to determine if ... | 2010 | 21049065 |
| expression analysis and knockdown of two antennal odorant-binding protein genes in aedes aegypti. | the presence and expression of odorant-binding proteins (obps) in the olfactory organs suggest that they play an important role in mosquito olfaction. however, no direct evidence has been found for their involvement in the host-seeking behavior of mosquitoes. it is important to establish a method in which a loss-of-function test can be performed to determine the possible role of these genes in olfaction. in this study, a double subgenomic sindbis virus expression system was used to reduce the ex ... | 2010 | 21062207 |
| dengue virus-induced autophagy regulates lipid metabolism. | autophagy influences numerous cellular processes, including innate and adaptive immunity against intracellular pathogens. however, some viruses, including dengue virus (denv), usurp autophagy to enhance their replication. the mechanism for a positive role of autophagy in denv infection is unclear. we present data that denv induction of autophagy regulates cellular lipid metabolism. denv infection leads to an autophagy-dependent processing of lipid droplets and triglycerides to release free fatty ... | 2010 | 21075353 |
| envelope lipid-packing as a critical factor for the biological activity and stability of alphavirus particles isolated from mammalian and mosquito cells. | alphaviruses are enveloped arboviruses. the viral envelope is derived from the host cell and is positioned between two icosahedral protein shells (t = 4). because the viral envelope contains glycoproteins involved in cell recognition and entry, the integrity of the envelope is critical for the success of the early events of infection. differing levels of cholesterol in different hosts leads to the production of alphaviruses with distinct levels of this sterol loaded in the envelope. using mayaro ... | 2010 | 21075845 |
| response to dengue virus infections altered by cytokine-like substances from mosquito cell cultures. | with both shrimp and commercial insects such as honey bees, it is known that stable, persistent viral infections characterized by absence of disease can sometimes shift to overt disease states as a result of various stress triggers and that this can result in serious economic losses. the main research interest of our group is to understand the dynamics of stable viral infections in shrimp and how they can be destabilized by stress. since there are no continuous cell lines for crustaceans, we hav ... | 2010 | 21078201 |
| role of the vacuolar-atpase in sindbis virus infection. | bafilomycin a(1) is a specific inhibitor of the vacuolar-atpase (v-atpase), which is responsible for ph homeostasis of the cell and for the acidification of endosomes. bafilomycin a(1) has been commonly used as a method of inhibition of infection by viruses known or suspected to follow the path of receptor-mediated endocytosis and low-ph-mediated membrane fusion. the exact method of entry for sindbis virus, the prototype alphavirus, remains undetermined. to further investigate the role of the v- ... | 2010 | 21084471 |
| double subgenomic alphaviruses expressing multiple fluorescent proteins using a rhopalosiphum padi virus internal ribosome entry site element. | double subgenomic sindbis virus (dssinv) vectors are widely used for the expression of proteins, peptides, and rna sequences. these recombinant rna viruses permit high level expression of a heterologous sequence in a wide range of animals, tissues, and cells. however, the alphavirus genome structure and replication strategy is not readily amenable to the expression of more than one heterologous sequence. the rhopalosiphum padi virus (rhpv) genome contains two internal ribosome entry site (ires) ... | 2010 | 21085714 |
| functional dissection of the alphavirus capsid protease: sequence requirements for activity. | the alphavirus capsid is multifunctional and plays a key role in the viral life cycle. the nucleocapsid domain is released by the self-cleavage activity of the serine protease domain within the capsid. all alphaviruses analyzed to date show this autocatalytic cleavage. here we have analyzed the sequence requirements for the cleavage activity of chikungunya virus capsid protease of genus alphavirus. | 2010 | 21087473 |
| antibody-directed lentiviral gene transduction in early immature hematopoietic progenitor cells. | the specific and efficient transduction of retroviral particles remains problematic for in vivo and ex vivo gene therapy studies, where the targeting cell population is a heterogeneous bulk population. | 2010 | 21104972 |
| inhibition of enveloped virus infection of cultured cells by valproic acid. | valproic acid (vpa) is a short-chain fatty acid commonly used for treatment of neurological disorders. as vpa can interfere with cellular lipid metabolism, its effect on the infection of cultured cells by viruses of seven viral families relevant to human and animal health, including eight enveloped and four nonenveloped viruses, was analyzed. vpa drastically inhibited multiplication of all the enveloped viruses tested, including the zoonotic lymphocytic choriomeningitis virus and west nile virus ... | 2010 | 21106740 |
| acute parvovirus b19 infection causes nonspecificity frequently in borrelia and less often in salmonella and campylobacter serology, posing a problem in diagnosis of infectious arthropathy. | several infectious agents may cause arthritis or arthropathy. for example, infection with borrelia burgdorferi, the etiologic agent of lyme disease, may in the late phase manifest as arthropathy. infections with campylobacter, salmonella, or yersinia may result in a postinfectious reactive arthritis. acute infection with parvovirus b19 (b19v) may likewise initiate transient or chronic arthropathy. all these conditions may be clinically indistinguishable from rheumatoid arthritis. here, we presen ... | 2010 | 21106777 |
| patented biological approaches for the therapeutic modulation of the 37 kda/67 kda laminin receptor. | the 37/67 kda laminin receptor precursor/laminin receptor (lrp/lr) represents a multifunctional protein located on the cell surface, in the cytosol and the nucleus. the receptor acts as a mediator for cell adhesion, cell proliferation and cell differentiation. it is a key player in invasion and adhesion, major functions of several important metastatic cancer types. the receptor hampers apoptosis thereby favoring cancer progression. lrp/lr plays a major role as a cell surface receptor in prion di ... | 2010 | 21110766 |
| structural biology: an alphavirus puzzle solved. | 2010 | 21124448 | |
| structural changes of envelope proteins during alphavirus fusion. | alphaviruses are enveloped rna viruses that have a diameter of about 700 å and can be lethal human pathogens. entry of virus into host cells by endocytosis is controlled by two envelope glycoproteins, e1 and e2. the e2-e1 heterodimers form 80 trimeric spikes on the icosahedral virus surface, 60 with quasi-three-fold symmetry and 20 coincident with the icosahedral three-fold axes arranged with t = 4 quasi-symmetry. the e1 glycoprotein has a hydrophobic fusion loop at one end and is responsible fo ... | 2010 | 21124457 |
| glycoprotein organization of chikungunya virus particles revealed by x-ray crystallography. | chikungunya virus (chikv) is an emerging mosquito-borne alphavirus that has caused widespread outbreaks of debilitating human disease in the past five years. chikv invasion of susceptible cells is mediated by two viral glycoproteins, e1 and e2, which carry the main antigenic determinants and form an icosahedral shell at the virion surface. glycoprotein e2, derived from furin cleavage of the p62 precursor into e3 and e2, is responsible for receptor binding, and e1 for membrane fusion. in the cont ... | 2010 | 21124458 |
| enhancement of protein vaccine potency by in vivo electroporation mediated intramuscular injection. | protein-based vaccines have emerged as a potentially promising approach for the generation of antigen-specific immune responses. however, due to their low immunogenicity, there is a need for innovative approaches to enhance protein-based vaccine potency. one approach to enhance protein-based vaccine potency is the employment of toll-like receptor ligands, such as cpg oligonucleotides, to activate the antigen-specific t cell immune responses. another approach involves employing a method capable o ... | 2010 | 21130752 |
| mutations in nsp1 and pe2 are critical determinants of ross river virus-induced musculoskeletal inflammatory disease in a mouse model. | the viral determinants of alphavirus-induced rheumatic disease have not been elucidated. we identified an rrv strain (dc5692) which, in contrast to the t48 strain, does not induce musculoskeletal inflammation in a mouse model of rrv disease. substitution of the rrv t48 strain nonstructural protein 1 (nsp1) coding sequence with that from strain dc5692 generated a virus that was attenuated in vivo despite similar viral loads in tissues. in contrast, substitution of the t48 pe2 coding region with t ... | 2010 | 21131014 |
| homeostatic regulation of glutamatergic transmission by dopamine d4 receptors. | alterations of synaptic transmission have been considered a core feature of mental disorders; thus, we examined the role of dopamine d(4) receptors, which is highly implicated in attention-deficit hyperactivity disorder and schizophrenia, in regulating synaptic functions of prefrontal cortex, a brain region critical for cognitive and emotional processes. we found that d(4) stimulation caused a profound depression or potentiation of ampa receptor-mediated excitatory synaptic transmission in prefr ... | 2010 | 21135234 |
| rigid amphipathic fusion inhibitors, small molecule antiviral compounds against enveloped viruses. | antiviral drugs targeting viral proteins often result in prompt selection for resistance. moreover, the number of viral targets is limited. novel antiviral targets are therefore needed. the unique characteristics of fusion between virion envelopes and cell membranes may provide such targets. like all fusing bilayers, viral envelopes locally adopt hourglass-shaped stalks during the initial stages of fusion, a process that requires local negative membrane curvature. unlike cellular vesicles, howev ... | 2010 | 20823220 |
| functional sindbis virus replicative complexes are formed at the plasma membrane. | formation of virus-specific replicative complexes (rcs) in infected cells is one of the most intriguing and important processes that determine virus replication and ultimately their pathogenesis on the molecular and cellular levels. alphavirus replication was known to lead to formation of so-called type 1 cytopathic vacuoles (cpv1s), whose distinguishing feature is the presence of numerous membrane invaginations (spherules) and accumulation of viral nonstructural proteins (nsps) at the cytoplasm ... | 2010 | 20826696 |
| human traf3 adaptor molecule deficiency leads to impaired toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. | tumor necrosis factor (tnf) receptor-associated factor 3 (traf3) functions downstream of multiple tnf receptors and receptors that induce interferon-α (ifn-α), ifn-β, and ifn-λ production, including toll-like receptor 3 (tlr3), which is deficient in some patients with herpes simplex virus-1 encephalitis (hse). mice lacking traf3 die in the neonatal period, preventing direct investigation of the role of traf3 in immune responses and host defenses in vivo. here, we report autosomal dominant, human ... | 2010 | 20832341 |
| amino acid substitutions in the e2 glycoprotein of sindbis-like virus xj-160 confer the ability to undergo heparan sulfate-dependent infection of mouse embryonic fibroblasts. | we have recently demonstrated an essential role of the domain of 145-150 amino acid in the e2 glycoprotein of sindbis virus in the interaction with cellular heparan sulfate (hs) and in the infection of mouse embryonic fibroblasts (mef) cells. in this study, we constructed and characterized the mutants of sindbis-like virus xj-160 in which tyr-146 and/or asn-149 in the e2 glycoprotein had been substituted with his and arg, respectively. unlike parental virus xj-160, mutants with either or both su ... | 2010 | 20836893 |
| differential roles of grip1a and grip1b in ampa receptor trafficking. | regulated trafficking controls ampa receptor (ampar) number at the postsynaptic membrane to modify the efficiency of synaptic transmission. the pdz proteins grip1 and the related abp-l/grip2 bind ampar subunit glua2, and have been proposed to play a role in ampar trafficking associated with long term depression (ltd) of synaptic transmission. both grip1 and abp-l/grip2 exist in different splice isoforms, including alternative 18 amino acid domains at the extreme n-terminus, which determine wheth ... | 2010 | 20837103 |
| noncanonical cytoplasmic processing of viral micrornas. | cellular utilization of rna interference (rnai) as a mechanism to combat virus infection is thought to be restricted to plants and invertebrates. in vertebrates, antiviral defenses are largely dependent on interferons (ifns), with the use of small rnas restricted to microrna (mirna)-mediated targeting of host transcripts. here we demonstrate that incorporation of a primary mirna into a cytoplasmic virus results in the formation of a dicer-dependent, dgcr8-independent, mature mirna capable of con ... | 2010 | 20841420 |
| respiratory syncytial virus induces host rna stress granules to facilitate viral replication. | mammalian cell cytoplasmic rna stress granules are induced during various conditions of stress and are strongly associated with regulation of host mrna translation. several viruses induce stress granules during the course of infection, but the exact function of these structures during virus replication is not well understood. in this study, we showed that respiratory syncytial virus (rsv) induced host stress granules in epithelial cells during the course of infection. we also showed that stress ... | 2010 | 20844027 |
| development of infectious cdna clones of salmonid alphavirus subtype 3. | abstract: | 2010 | 20858233 |
| type b coxsackieviruses and their interactions with the innate and adaptive immune systems. | coxsackieviruses are important human pathogens, and their interactions with the innate and adaptive immune systems are of particular interest. many viruses evade some aspects of the innate response, but coxsackieviruses go a step further by actively inducing, and then exploiting, some features of the host cell response. furthermore, while most viruses encode proteins that hinder the effector functions of adaptive immunity, coxsackieviruses and their cousins demonstrate a unique capacity to almos ... | 2010 | 20860480 |
| coxsackievirus infection induces autophagy-like vesicles and megaphagosomes in pancreatic acinar cells in vivo. | autophagy can play an important part in protecting host cells during virus infection, and several viruses have developed strategies by which to evade or even exploit this homeostatic pathway. tissue culture studies have shown that poliovirus, an enterovirus, modulates autophagy. herein, we report on in vivo studies that evaluate the effects on autophagy of coxsackievirus b3 (cvb3). we show that in pancreatic acinar cells, cvb3 induces the formation of abundant small autophagy-like vesicles and p ... | 2010 | 20861268 |
| development of a new tacaribe arenavirus infection model and its use to explore antiviral activity of a novel aristeromycin analog. | a growing number of arenaviruses can cause a devastating viral hemorrhagic fever (vhf) syndrome. they pose a public health threat as emerging viruses and because of their potential use as bioterror agents. all of the highly pathogenic new world arenaviruses (nwa) phylogenetically segregate into clade b and require maximum biosafety containment facilities for their study. tacaribe virus (tcrv) is a nonpathogenic member of clade b that is closely related to the vhf arenaviruses at the amino acid l ... | 2010 | 20862280 |
| when autophagy meets viruses: a double-edged sword with functions in defense and offense. | autophagy is a ubiquitous catabolic process that ensures organism's well-being by sequestering a wide array of undesired intracellular constituents into double-membrane vesicles termed autophagosomes for lysosomal degradation. interest in autophagy research has recently gained momentum as it is increasingly being recognized to play fundamental roles in diverse aspects of human pathophysiology including virus infection and its subsequent complications. this review discusses recent advances in aut ... | 2010 | 20865416 |
| dendritic cells transfected with her2 antigen-encoding rna replicons cross-prime cd8 t cells and protect mice against tumor challenge. | antigen-specific t cells can be induced by direct priming and cross-priming. to investigate cross-priming as a vaccination approach dendritic cells were transfected with cytopathogenic viral rna-replicons that expressed domains of the tumor-associated her2-antigen and injected into mhc-discordant mice that did not allow direct priming. upon tumor challenge 75% of the vaccinated, but none of the mock-vaccinated mice remained tumor-free. the anti-tumor effect required t cells and correlated with t ... | 2010 | 20887827 |
| kv4.2 block of long-term potentiation is partially dependent on synaptic nmda receptor remodeling. | proper expression of synaptic nmda receptors (nmdars) is necessary to regulate synaptic ca²(+) influx and the induction the long-term potentiation (ltp) in the mammalian hippocampus. previously we reported that expressing the a-type k(+) channel subunit kv4.2 in ca1 neurons of organotypic slice cultures reduced synaptic nr2b-containing nmdar expression and completely blocked ltp induced by a pairing protocol. as pretreatment with an nmdar antagonist (apv) overnight blocked the reduction of nr2b- ... | 2010 | 20920553 |
| autophagy in cigarette smoke-induced chronic obstructive pulmonary disease. | the molecular and cellular mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (copd) remain incompletely understood. we have investigated the potential role of macro-autophagy, a cellular homeostatic mechanism, in copd and cigarette smoke-induced lung-cell injury. autophagy is a dynamic process for the turnover of organelles and proteins, which regenerates metabolic precursors through the lysosomal-dependent catabolism of cellular macromolecules. it is typically asso ... | 2010 | 20923337 |
| antibody to the e3 glycoprotein protects mice against lethal venezuelan equine encephalitis virus infection. | six monoclonal antibodies were isolated that exhibited specificity for a furin cleavage site deletion mutant (v3526) of venezuelan equine encephalitis virus (veev). these antibodies comprise a single competition group and bound the e3 glycoprotein of veev subtype i viruses but failed to bind the e3 glycoprotein of other alphaviruses. these antibodies neutralized v3526 virus infectivity but did not neutralize the parental strain of trinidad donkey (trd) veev. however, the e3-specific antibodies d ... | 2010 | 20926570 |
| morphine- and camkii-dependent enhancement of girk channel signaling in hippocampal neurons. | g-protein-gated inwardly rectifying potassium (girk) channels, which help control neuronal excitability, are important for the response to drugs of abuse. here, we describe a novel pathway for morphine-dependent enhancement of girk channel signaling in hippocampal neurons. morphine treatment for ∼20 h increased the colocalization of girk2 with psd95, a dendritic spine marker. western blot analysis and quantitative immunoelectron microscopy revealed an increase in girk2 protein and targeting to d ... | 2010 | 20926668 |
| pathogenomics of culex quinquefasciatus and meta-analysis of infection responses to diverse pathogens. | the mosquito culex quinquefasciatus poses a substantial threat to human and veterinary health as a primary vector of west nile virus (wnv), the filarial worm wuchereria bancrofti, and an avian malaria parasite. comparative phylogenomics revealed an expanded canonical c. quinquefasciatus immune gene repertoire compared with those of aedes aegypti and anopheles gambiae. transcriptomic analysis of c. quinquefasciatus genes responsive to wnv, w. bancrofti, and non-native bacteria facilitated an unpr ... | 2010 | 20929811 |
| infections of people with complement deficiencies and patients who have undergone splenectomy. | the complement system comprises several fluid-phase and membrane-associated proteins. under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as "nonself" in an attempt to minimize damage to bystander host cells. membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes "tagged" with complement fra ... | 2010 | 20930072 |
| the lymphoid chemokine, cxcl13, is dispensable for the initial recruitment of b cells to the acutely inflamed central nervous system. | cases of progressive multifocal leukoencephalopathy can occur in patients treated with the b cell depleting anti-cd20 antibody, rituximab, highlighting the importance of b cell surveillance of the central nervous system (cns). the lymphoid chemokine, cxcl13, is critical for b cell recruitment and functional organization of peripheral lymphoid tissues, and cxcl13 levels are often elevated in the inflamed cns. to more directly investigate the role of cxcl13 in cns b cell migration, its role in ani ... | 2010 | 20933590 |
| emerging role of isg15 in antiviral immunity. | cells express a plethora of interferon-stimulated genes (isgs) in response to viral infection. among these is isg15, a ubiquitin-like protein (ubl) that can be covalently attached to both host and viral proteins. here we review recent advances toward understanding the role and mechanism of isg15 modification in antiviral defense. | 2010 | 20946978 |
| evaluation of the influenza a replicon for transient expression of recombinant proteins in mammalian cells. | recombinant protein expression in mammalian cells has become a very important technique over the last twenty years. it is mainly used for production of complex proteins for biopharmaceutical applications. transient recombinant protein expression is a possible strategy to produce high quality material for preclinical trials within days. viral replicon based expression systems have been established over the years and are ideal for transient protein expression. in this study we describe the evaluat ... | 2010 | 20949004 |
| dengue virus ensures its fusion in late endosomes using compartment-specific lipids. | many enveloped viruses invade cells via endocytosis and use different environmental factors as triggers for virus-endosome fusion that delivers viral genome into cytosol. intriguingly, dengue virus (den), the most prevalent mosquito-borne virus that infects up to 100 million people each year, fuses only in late endosomes, while activation of den protein fusogen glycoprotein e is triggered already at ph characteristic for early endosomes. are there any cofactors that time den fusion to virion ent ... | 2010 | 20949067 |
| the isg56/ifit1 gene family. | the isg56/ifit1 family of genes is clustered on human chromosome 10 and is comprised of 4 members, isg56/ifit1, isg54/ifit2, isg60/ifit3, and isg58/ifit5, whose homologs are evolutionarily conserved from mammals to amphibians. while these genes are normally silent in most cell types, their transcription is strongly induced by interferons, virus infection, and molecular patterns such as double-stranded rna or lipopolysaccharides. the encoded p56 family proteins are characterized by multiple repea ... | 2010 | 20950130 |
| differential protein modulation in midguts of aedes aegypti infected with chikungunya and dengue 2 viruses. | arthropod borne virus infections cause several emerging and resurgent infectious diseases. among the diseases caused by arboviruses, dengue and chikungunya are responsible for a high rate of severe human diseases worldwide. the midgut of mosquitoes is the first barrier for pathogen transmission and is a target organ where arboviruses must replicate prior to infecting other organs. a proteomic approach was undertaken to characterize the key virus/vector interactions and host protein modifications ... | 2010 | 20957153 |
| chikungunya virus induces ips-1-dependent innate immune activation and protein kinase r-independent translational shutoff. | chikungunya virus (chikv) is an arthritogenic mosquito-transmitted alphavirus that is undergoing reemergence in areas around the indian ocean. despite the current and potential danger posed by this virus, we know surprisingly little about the induction and evasion of chikv-associated antiviral immune responses. with this in mind we investigated innate immune reactions to chikv in human fibroblasts, a demonstrable in vivo target of virus replication and spread. we show that chikv infection leads ... | 2010 | 20962078 |
| in vitro and in vivo studies identify important features of dengue virus pr-e protein interactions. | flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prm protein to pr and m. the peripheral pr peptide remains bound to virus at low ph and inhibits virus-membrane interaction. upon exocytosis, the release of pr at neutral ph completes virus maturation to an infectious particle. together this evidence suggests that pr may shield the flavivirus fusi ... | 2010 | 20975939 |
| regulation of stim1 and soce by the ubiquitin-proteasome system (ups). | the ubiquitin proteasome system (ups) mediates the majority of protein degradation in eukaryotic cells. the ups has recently emerged as a key degradation pathway involved in synapse development and function. in order to better understand the function of the ups at synapses we utilized a genetic and proteomic approach to isolate and identify novel candidate ups substrates from biochemically purified synaptic membrane preparations. using these methods, we have identified stromal interacting molecu ... | 2010 | 20976103 |
| high-resolution functional mapping of the venezuelan equine encephalitis virus genome by insertional mutagenesis and massively parallel sequencing. | we have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the venezuelan equine encephalitis virus (veev) genome. we initially used a capillary electrophoresis method to gain insight into the role of the veev nonstructural protein 3 (nsp3) in viral replication. we identified several regions in nsp3 that are intolerant t ... | 2010 | 20976195 |
| rnai-mediated immunity provides strong protection against the negative-strand rna vesicular stomatitis virus in drosophila. | activation of innate antiviral responses in multicellular organisms relies on the recognition of structural differences between viral and cellular rnas. double-stranded (ds)rna, produced during viral replication, is a well-known activator of antiviral defenses and triggers interferon production in vertebrates and rnai in invertebrates and plants. previous work in mammalian cells indicates that negative-strand rna viruses do not appear to generate dsrna, and that activation of innate immunity is ... | 2010 | 20978209 |
| r5 hiv env and vesicular stomatitis virus g protein cooperate to mediate fusion to naive cd4+ t cells. | naïve cd4(4) t cells are resistant to both hiv r5 env and vesicular stomatitis virus g protein (vsv-g)-mediated fusion. however, viral particles carrying both hiv r5 env and vsv-g infect naïve cells by an unexplained mechanism. we show that vsv-g-pseudotyped virus cannot fuse to unstimulated cells because the viral particles cannot be endocytosed. however, virions carrying both hiv r5 env and vsv-g can fuse because cd4 binding allows viral uptake. our findings reveal a unique mechanism by which ... | 2010 | 20980513 |
| intracellular calcium and calmodulin link brain-derived neurotrophic factor to p70s6 kinase phosphorylation and dendritic protein synthesis. | the mammalian target of rapamycin (mtor)/p70s6 kinase (s6k) pathway plays an important role in brain-derived neurotrophic factor (bdnf)-mediated protein synthesis and neuroplasticity. although many aspects of neuronal function are regulated by intracellular calcium ([ca(2+)](i)) and calmodulin (cam), their functions in bdnf-induced phosphorylation of p70s6k and protein synthesis are largely unknown. here, we report that bdnf, via trkb-dependent activation of mtor, induces sustained phosphorylati ... | 2010 | 20029971 |
| gltscr2/pict-1, a putative tumor suppressor gene product, induces the nucleolar targeting of the kaposi's sarcoma-associated herpesvirus ks-bcl-2 protein. | ks-bcl-2, encoded by kaposi's sarcoma-associated herpesvirus (kshv), is a structural and functional homologue of the bcl-2 family of apoptosis regulators. like several other bcl-2 family members, ks-bcl-2 protects cells from apoptosis and autophagy. using a yeast two-hybrid screen and coimmunoprecipitation assays, we identified a novel ks-bcl-2-interacting protein, referred to as protein interacting with carboxyl terminus 1 (pict-1), encoded by a candidate tumor suppressor gene, gltscr2. confoca ... | 2010 | 20042497 |
| dissemination of spotted fever rickettsia agents in europe by migrating birds. | migratory birds are known to play a role as long-distance vectors for many microorganisms. to investigate whether this is true of rickettsial agents as well, we characterized tick infestation and gathered ticks from 13,260 migratory passerine birds in sweden. a total of 1127 ixodes spp. ticks were removed from these birds and the extracted dna from 957 of them was available for analyses. the dna was assayed for detection of rickettsia spp. using real-time pcr, followed by dna sequencing for spec ... | 2010 | 20052286 |
| involvement of ceramide in the propagation of japanese encephalitis virus. | japanese encephalitis virus (jev) is a mosquito-borne rna virus and one of the most important flaviviruses in the medical and veterinary fields. although cholesterol has been shown to participate in both the entry and replication steps of jev, the mechanisms of infection, including the cellular receptors of jev, remain largely unknown. to clarify the infection mechanisms of jev, we generated pseudotype (jevpv) and recombinant (jevrv) vesicular stomatitis viruses bearing the jev envelope protein. ... | 2010 | 20053738 |
| in vitro synthesis of sindbis virus genomic and subgenomic rnas: influence of nsp4 mutations and nucleoside triphosphate concentrations. | two positive-strand mrnas are made in sindbis virus-infected cells, the genomic (g) rna and the subgenomic (sg) rna. in mosquito cells infected with wild-type (wt) sindbis virus, the latter is made in excess over the former; however, in cells infected with svpzf or svcpc more g rna is made than sg rna. use was made of in vitro systems to investigate the effects of the svpzf and svcpc mutations on the synthesis of sg and g rnas. our findings indicate that under standard reaction conditions, the s ... | 2010 | 20053747 |
| gene therapy for acute myeloid leukemia using sindbis vectors expressing a fusogenic membrane glycoprotein. | aml has a dismal prognosis. it was previously shown that the expression of gene coding for the hyperfusogenic gibbon ape leukemia virus envelope glycoprotein (galv.fus) can efficiently kill leukemic cells. however, target killing effect of galv.fus on leukemia cells may be limited. viral vectors, such as retroviruses and adenoviruses, have been developed to deliver heterologous genes into tumors in vivo, but these vectors have some limitations for gene therapy of leukemia. another virus that has ... | 2010 | 20061812 |
| genetic analysis of chikungunya viruses imported to mainland china in 2008. | chikungunya virus (chikv) has caused large outbreaks worldwide in recent years, especially on the islands of the indian ocean and india. the virus is transmitted by mosquitoes (aedes aegypti), which are widespread in china, with an especially high population density in southern china. analyses of full-length viral sequences revealed the acquisition of a single adaptive mutation providing a selective advantage for the transmission of chikv by this species. no outbreaks due to the local transmissi ... | 2010 | 20078896 |
| the toll immune signaling pathway control conserved anti-dengue defenses across diverse ae. aegypti strains and against multiple dengue virus serotypes. | dengue virus has become one of the most important arboviral pathogens affecting the world today. the virus is transmitted among humans by the mosquitoes aedes aegypti and ae. albopictus. like other vector-borne pathogens, this virus encounters innate immune defenses within the mosquito vector that limit infection. we have previously demonstrated the involvement of the toll pathway in the anti-dengue defense at 7 days after infection. in the present study, we have investigated the activity of thi ... | 2010 | 20079370 |
| virus discovery by deep sequencing and assembly of virus-derived small silencing rnas. | in response to infection, invertebrates process replicating viral rna genomes into sirnas of discrete sizes to guide virus clearance by rna interference. here, we show that viral sirnas sequenced from fruit fly, mosquito, and nematode cells were all overlapping in sequence, suggesting a possibility of using sirnas for viral genome assembly and virus discovery. to test this idea, we examined contigs assembled from published small rna libraries and discovered five previously undescribed viruses fr ... | 2010 | 20080648 |
| regulation of synaptic structure and function by palmitoylated ampa receptor binding protein. | ampa receptor binding protein (abp) is a multi-pdz domain scaffold that binds and stabilizes ampa receptor (ampar) glur2/3 subunits at synapses. a palmitoylated n-terminal splice variant (pabp-l) concentrates in spine heads, whereas a non-palmitoylated form (abp-l) is intracellular. we show that postsynaptic sindbis viral expression of pabp-l increased ampar mediated mepsc amplitude and frequency and elevated surface levels of glur1 and glur2, suggesting an increase in ampa receptors at individu ... | 2010 | 20083202 |
| lentiviral vectors for immune cells targeting. | lentiviral vectors (lvs) are efficient gene delivery vehicles suitable for delivering long-term transgene expression in various cell types. engineering lvs to have the capacity to transduce specific cell types is of great interest to advance the translation of lvs toward the clinic. here we provide an overview of innovative approaches to target lvs to cells of the immune system. in this overview we distinguish between two types of lv targeting strategies: (i) targeting of the vectors to specific ... | 2010 | 20085508 |
| epidemiological analysis of mosquito-borne pogosta disease in finland, 2009. | pogosta disease is a viral disease caused by a mosquito-borne alphavirus, sindbis virus (sinv), and large human outbreaks of sinv infection have emerged in finland every seven years. after a major outbreak in 2002 an epidemic was expected to take place in 2009. data from the national infectious disease registry showed a small outbreak in humans in 2009 with a total of 105 reported cases but the seven-year cycle did not recur as anticipated. | 2010 | 20085692 |
| recent advances in lentiviral vector development and applications. | lentiviral vectors (lvs) have emerged as potent and versatile vectors for ex vivo or in vivo gene transfer into dividing and nondividing cells. robust phenotypic correction of diseases in mouse models has been achieved paving the way toward the first clinical trials. lvs can deliver genes ex vivo into bona fide stem cells, particularly hematopoietic stem cells, allowing for stable transgene expression upon hematopoietic reconstitution. they are also useful to generate induced pluripotent stem ce ... | 2010 | 20087315 |
| enhancing the therapeutic effect against ovarian cancer through a combination of viral oncolysis and antigen-specific immunotherapy. | cancer therapy using oncolytic viruses represents a promising new approach for controlling ovarian cancer. in this study, we have circumvented the limitation of repeated vaccination by employing different virus vectors, semliki forest virus (sfv) and vaccinia virus (vv) for boosting the immune response. we found that infection of tumor-bearing mice with vv followed by infection with sfv or vice versa leads to enhanced antitumor effects against murine ovarian surface epithelial carcinoma (mosec) ... | 2010 | 20087318 |
| recovery from viral encephalomyelitis: immune-mediated noncytolytic virus clearance from neurons. | viral encephalomyelitis is caused by virus infections of neurons in the brain and spinal cord. recovery is dependent on immune-mediated control and clearance of virus from these terminally differentiated essential cells. preservation of neuronal function is essential for prevention of neurologic sequelae such as paralysis, seizures and cognitive deficits. using the model system of sindbis virus-induced encephalomyelitis in mice, we have shown that immune-mediated clearance of infectious virus fr ... | 2010 | 20087684 |
| rna interference-based therapeutics for human immunodeficiency virus hiv-1 treatment: synthetic sirna or vector-based shrna? | despite the clinical benefits of highly active antiretroviral therapy (haart), the prospect of life-long antiretroviral treatment poses significant problems, which has spurred interest in developing new drugs and strategies to treat hiv infection and eliminate persistent viral reservoirs. rnai has emerged as a therapeutic possibility for hiv. | 2010 | 20088715 |
| the beclin 1 interactome. | the mammalian ortholog of yeast atg6/vps30, beclin 1, is an essential autophagy protein that has been linked to diverse biological processes, including immunity, development, tumor suppression, lifespan extension, and protection against certain cardiac and neurodegenerative diseases. in recent years, major advances have been made in identifying components of functionally distinct beclin 1/class iii phosphatidylinositol 3-kinase complexes, in characterizing the molecular regulation of interaction ... | 2010 | 20097051 |
| modulation of type i ifn induction by a virulence determinant within the alphavirus nsp1 protein. | alphaviruses are mosquito-borne viruses that cause serious human and animal diseases. previous studies demonstrated that a determinant within the nsp1/nsp2 cleavage domain of the virulent sindbis ar86 virus played a key role in regulating adult mouse virulence without adversely affecting viral replication. additional characterization of this determinant demonstrated that a virus with the attenuating mutation induced more type i ifn production both in vivo and in vitro. interestingly, this phenot ... | 2010 | 20097400 |
| cell-specific targeting of lentiviral vectors mediated by fusion proteins derived from sindbis virus, vesicular stomatitis virus, or avian sarcoma/leukosis virus. | the ability to efficiently and selectively target gene delivery vectors to specific cell types in vitro and in vivo remains one of the formidable challenges in gene therapy. we pursued two different strategies to target lentiviral vector delivery to specific cell types. in one of the strategies, vector particles bearing a membrane-bound stem cell factor sequence plus a separate fusion protein based either on sindbis virus strain tr339 glycoproteins or the vesicular stomatitis virus g glycoprotei ... | 2010 | 20100344 |
| incongruent fitness landscapes, not tradeoffs, dominate the adaptation of vesicular stomatitis virus to novel host types. | host radiation refers to the ability of parasites to adapt to new environments and expand or change their niches. adaptation to one specific environment may involve a loss in adaptation to a second environment. thus, fitness costs may impose limits to niche expansion and constitute the cost of specialization. several reports have addressed the cost of host radiation in vesicular stomatitis virus (vsv), but in some cases the experimental setup may have resulted in the overestimation of fitness co ... | 2010 | 20107014 |
| a chimeric alphavirus replicon particle vaccine expressing the hemagglutinin and fusion proteins protects juvenile and infant rhesus macaques from measles. | measles remains a major cause of child mortality, in part due to an inability to vaccinate young infants with the current live attenuated virus vaccine (lav). to explore new approaches to infant vaccination, chimeric venezuelan equine encephalitis/sindbis virus (vee/sin) replicon particles were used to express the hemagglutinin (h) and fusion (f) proteins of measles virus (mv). juvenile rhesus macaques vaccinated intradermally with a single dose of vee/sin expressing h or h and f proteins (vee/s ... | 2010 | 20130066 |
| sindbis virus: propagation, quantification, and storage. | the prototype of the alphaviruses, sindbis virus, has a broad host range. in nature, sindbis virus shuttles from an insect vector to a vertebrate host and back to the insect vector in a complex transmission cycle. sindbis virus must, therefore, be able to replicate in two biochemically and genetically divergent hosts, invertebrates and vertebrates. in the laboratory, sindbis grows to high titers in a large variety of cultured cells of both vertebrate and invertebrate origin. sindbis virus is eas ... | 2010 | 20131223 |
| isg15 conjugation system targets the viral ns1 protein in influenza a virus-infected cells. | isg15 is an ifn-alpha/beta-induced, ubiquitin-like protein that is conjugated to a wide array of cellular proteins through the sequential action of three conjugation enzymes that are also induced by ifn-alpha/beta. recent studies showed that isg15 and/or its conjugates play an important role in protecting cells from infection by several viruses, including influenza a virus. however, the mechanism by which isg15 modification exerts antiviral activity has not been established. here we extend the r ... | 2010 | 20133869 |
| transmission potential of two chimeric western equine encephalitis vaccine candidates in culex tarsalis. | western equine encephalitis virus (weev) is a zoonotic alphavirus that circulates in western north america between passerine birds and mosquitoes, primarily culex tarsalis. since it was isolated in 1930, weev has caused tens of thousands of equine deaths in addition to thousands of human cases. in addition because weev is a virus of agricultural importance in addition to a public health threat, we developed two live-attenuated chimeric vaccine candidates that have been shown to be immunogenic an ... | 2010 | 20134017 |
| efficient, trans-complementing packaging systems for chimeric, pseudoinfectious dengue 2/yellow fever viruses. | in our previous studies, we have stated to build a new strategy for developing defective, pseudoinfectious flaviviruses (pivs) and applying them as a new type of vaccine candidates. pivs combined the efficiency of live vaccines with the safety of inactivated or subunit vaccines. the results of the present work demonstrate further development of chimeric pivs encoding dengue virus 2 (den2v) glycoproteins and yellow fever virus (yfv)-derived replicative machinery as potential vaccine candidates. t ... | 2010 | 20137799 |
| visualization of feline calicivirus replication in real-time with recombinant viruses engineered to express fluorescent reporter proteins. | caliciviruses are non-enveloped, icosahedral viruses with a single-stranded, positive sense rna genome. transposon-mediated insertional mutagenesis was used to insert a transprimer sequence into random sites of an infectious full-length cdna clone of the feline calicivirus (fcv) genome. a site in the lc gene (encoding the capsid leader protein) of the fcv genome was identified that could tolerate foreign insertions, and two viable recombinant fcv variants expressing lc fused either to acgfp, or ... | 2010 | 20137802 |
| disrupted-in-schizophrenia 1 (disc1) regulates spines of the glutamate synapse via rac1. | synaptic spines are dynamic structures that regulate neuronal responsiveness and plasticity. we examined the role of the schizophrenia risk factor disc1 in the maintenance of spine morphology and function. we found that disc1 anchored kalirin-7 (kal-7), regulating access of kal-7 to rac1 and controlling the duration and intensity of rac1 activation in response to nmda receptor activation in both cortical cultures and rat brain in vivo. these results explain why rac1 and its activator (kal-7) ser ... | 2010 | 20139976 |
| lentiviral vectors in gene therapy: their current status and future potential. | the concept of gene therapy originated in the mid twentieth century and was perceived as a revolutionary technology with the promise to cure almost any disease of which the molecular basis was understood. since then, several gene vectors have been developed and the feasibility of gene therapy has been shown in many animal models of human disease. however, clinical efficacy could not be demonstrated until the beginning of the new century in a small-scale clinical trial curing an otherwise fatal i ... | 2010 | 20143172 |