Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
|---|
| acute in vivo genetic rescue demonstrates that phosphorylation of rim1alpha serine 413 is not required for mossy fiber long-term potentiation. | while presynaptic, protein kinase a (pka)-dependent, long-term plasticity has been described in numerous brain regions, the target(s) of pka and the molecular mechanisms leading to sustained changes in neurotransmitter release remain elusive. here, we acutely reconstitute mossy fiber long-term potentiation (mfltp) de novo in the mature brains of mutant mice that normally lack this form of plasticity. these results demonstrate that rim1alpha, a presynaptic scaffold protein and a potential pka tar ... | 2010 | 20164339 |
| a short n-terminal peptide motif on flavivirus nonstructural protein ns1 modulates cellular targeting and immune recognition. | flavivirus ns1 is a versatile nonstructural glycoprotein, with intracellular ns1 functioning as an essential cofactor for viral replication and cell surface and secreted ns1 antagonizing complement activation. even though ns1 has multiple functions that contribute to virulence, the genetic determinants that regulate the spatial distribution of ns1 in cells among different flaviviruses remain uncharacterized. here, by creating a panel of west nile virus-dengue virus (wnv-denv) ns1 chimeras and si ... | 2010 | 20592095 |
| antibody-mediated targeted gene transfer to nmda nr1-containing neurons in rat neocortex by helper virus-free hsv-1 vector particles containing a chimeric hsv-1 glycoprotein c-staphylococcus a protein. | because of the heterogeneous cellular composition of the brain, and especially the forebrain, cell type-specific expression will benefit many potential applications of direct gene transfer. the two prevalent approaches for achieving cell type-specific expression are using a cell type-specific promoter or targeting gene transfer to a specific cell type. targeted gene transfer with herpes simplex virus (hsv-1) vectors modifies glycoprotein c (gc) to replace the heparin binding domain, which binds ... | 2010 | 20599821 |
| advances in rift valley fever research: insights for disease prevention. | the purpose was to review recent research on rift valley fever virus (rvfv) infection, encompassing four main areas: epidemiology and outbreak prediction, viral pathogenesis, human diagnostics and therapeutics, and vaccine and therapeutic candidates. | 2010 | 20613512 |
| t cells facilitate recovery from venezuelan equine encephalitis virus-induced encephalomyelitis in the absence of antibody. | venezuelan equine encephalitis virus (veev) is a mosquito-borne rna virus of the genus alphavirus that is responsible for a significant disease burden in central and south america through sporadic outbreaks into human and equid populations. for humans, 2 to 4% of cases are associated with encephalitis, and there is an overall case mortality rate of approximately 1%. in mice, replication of the virus within neurons of the central nervous system (cns) leads to paralyzing, invariably lethal encepha ... | 2010 | 20181704 |
| mucosal priming of newborn mice with s. typhi ty21a expressing anthrax protective antigen (pa) followed by parenteral pa-boost induces b and t cell-mediated immunity that protects against infection bypassing maternal antibodies. | the currently licensed anthrax vaccine has several limitations and its efficacy has been proven only in adults. effective immunization of newborns and infants requires adequate stimulation of their immune system, which is competent but not fully activated. we explored the use of the licensed live attenuated s. typhi vaccine strain ty21a expressing bacillus anthracis protective antigen [ty21a(pa)] followed pa-alum as a strategy for immunizing the pediatric population. newborn mice primed with a s ... | 2010 | 20619377 |
| structure of the recombinant alphavirus western equine encephalitis virus revealed by cryoelectron microscopy. | western equine encephalitis virus (weev; togaviridae, alphavirus) is an enveloped rna virus that is typically transmitted to vertebrate hosts by infected mosquitoes. weev is an important cause of viral encephalitis in humans and horses in the americas, and infection results in a range of disease, from mild flu-like illnesses to encephalitis, coma, and death. in addition to spreading via mosquito vectors, human weev infections can potentially occur directly via aerosol transmission. due to its ae ... | 2010 | 20631130 |
| identification of a dominant negative inhibitor of human zinc finger antiviral protein reveals a functional endogenous pool and critical homotypic interactions. | the zinc finger antiviral protein (zap) is a host factor with potent antiviral activity when overexpressed in cells. zap blocks replication of the prototype alphavirus sindbis virus (sinv) at a step at or before translation of the incoming viral genome. the mechanism of zap anti-sinv activity and the determinants of its antiviral function, however, have not been defined. here, we have identified a dominant negative inhibitor of human zap. rat zap with a cysteine-to-arginine mutation at position ... | 2010 | 20181706 |
| translation driven by picornavirus ires is hampered from sindbis virus replicons: rescue by poliovirus 2a protease. | alphavirus replicons are very useful for analyzing different aspects of viral molecular biology. they are also useful tools in the development of new vaccines and highly efficient expression of heterologous genes. we have investigated the translatability of sindbis virus (sv) subgenomic mrna bearing different 5'-untranslated regions, including several viral internal ribosome entry sites (iress) from picornaviruses, hepatitis c virus, and cricket paralysis virus. our findings indicate that all th ... | 2010 | 20643140 |
| the length of and nonhydrophobic residues in the transmembrane domain of dengue virus envelope protein are critical for its retention and assembly in the endoplasmic reticulum. | the morphogenesis of many enveloped viruses, in which viral nucleocapsid complex interacts with envelope (e) protein, is known to take place at various sites along the secretory pathway. how viral e protein retains in a particular intracellular organelle for assembly remains incompletely understood. in this study, we investigated determinants in the e protein of dengue virus (denv) for its retention and assembly in the endoplasmic reticulum (er). a chimeric experiment between cd4 and denv precur ... | 2010 | 20181718 |
| identification of a dendrimeric heparan sulfate-binding peptide that inhibits infectivity of genital types of human papillomaviruses. | peptide dendrimers consist of a peptidyl branching core and/or covalently attached surface functional units. they show a variety of biological properties, including antiviral activity. in this study, a minilibrary of linear, dimeric, and dendrimeric peptides containing clusters of basic amino acids was evaluated for in vitro activity against human papillomaviruses (hpvs). the peptide dendrimer sb105-a10 was found to be a potent inhibitor of genital hpv types (i.e., types 16, 18, and 6) in pseudo ... | 2010 | 20643894 |
| the first human epitope map of the alphaviral e1 and e2 proteins reveals a new e2 epitope with significant virus neutralizing activity. | venezuelan equine encephalitis virus (veev) is responsible for vee epidemics that occur in south and central america and the u.s. the veev envelope contains two glycoproteins e1 (mediates cell membrane fusion) and e2 (binds receptor and elicits virus neutralizing antibodies). previously we constructed e1 and e2 epitope maps using murine monoclonal antibodies (mmabs). six e2 epitopes (e2(c,d,e,f,g,h)) bound veev-neutralizing antibody and mapped to amino acids (aa) 182-207. nothing is known about ... | 2010 | 20644615 |
| arboviral encephalitides: transmission, emergence, and pathogenesis. | arthropod-borne viruses (arboviruses) are of paramount concern as a group of pathogens at the forefront of emerging and re-emerging diseases. although some arboviral infections are asymptomatic or present with a mild influenza-like illness, many are important human and veterinary pathogens causing serious illness ranging from rash and arthritis to encephalitis and hemorrhagic fever. here, we discuss arboviruses from diverse families (flaviviruses, alphaviruses, and the bunyaviridae) that are cau ... | 2010 | 20652430 |
| imaging multiple intermediates of single-virus membrane fusion mediated by distinct fusion proteins. | membrane fusion plays an essential role in the entry of enveloped viruses into target cells. the merging of viral and target cell membranes is catalyzed by viral fusion proteins, which involves multiple sequential steps in the fusion process. however, the fusion mechanisms mediated by different fusion proteins involve multiple transient intermediates that have not been well characterized. here, we report a synthetic virus platform that allows us to better understand the different fusion mechanis ... | 2010 | 20232362 |
| aedes aegypti saliva alters leukocyte recruitment and cytokine signaling by antigen-presenting cells during west nile virus infection. | west nile virus (wnv) is transmitted during mosquito bloodfeeding. consequently, the first vertebrate cells to contact wnv are cells in the skin, followed by those in the draining lymph node. macrophages and dendritic cells are critical early responders in host defense against wnv infection, not just because of their role in orchestrating the immune response, but also because of their importance as sites of early peripheral viral replication. antigen-presenting cell (apc) signals have a profound ... | 2010 | 20661470 |
| hnrnp a1 interacts with the genomic and subgenomic rna promoters of sindbis virus and is required for the synthesis of g and sg rna. | sindbis virus (sv) is the prototype of alphaviruses which are a group of widely distributed human and animal pathogens. heterogeneous nuclear ribonucleoprotein (hnrnp) a1 is an rna-binding protein that shuttles between the nucleus and the cytoplasm. our recent studies found that hnrnp a1 relocates from nucleus to cytoplasm in sindbis virus (sv)-infected cells. hnrnp a1 binds to the 5' utr of sv rna and facilitates the viral rna replication and translation. | 2010 | 20663119 |
| antagonism of the complement component c4 by flavivirus nonstructural protein ns1. | the complement system plays an essential protective role in the initial defense against many microorganisms. flavivirus ns1 is a secreted nonstructural glycoprotein that accumulates in blood, is displayed on the surface of infected cells, and has been hypothesized to have immune evasion functions. herein, we demonstrate that dengue virus (denv), west nile virus (wnv), and yellow fever virus (yfv) ns1 attenuate classical and lectin pathway activation by directly interacting with c4. binding of ns ... | 2010 | 20308361 |
| introduction of green fluorescent protein (gfp) into hippocampal neurons through viral infection. | expression of green fluorescent protein (gfp), its more fluorescent mutant forms (e.g., egfp [enhanced gfp]), or their fusion protein derivatives, affords a number of informative possibilities in cellular neuroscience. egfp is a soluble protein and appears to be homogeneously distributed within the cytosol of neurons when expressed. thus, it reveals the structure of the neuron, including the cell body, and axonal and dendritic arbors. it is also sufficiently bright to reveal detailed structures ... | 2010 | 20360360 |
| trimethylguanosine capping selectively promotes expression of rev-dependent hiv-1 rnas. | 5'-mrna capping is an early modification that affects pre-mrna synthesis/splicing, rna cytoplasmic transport, and mrna translation and turnover. in eukaryotes, a 7-methylguanosine (m7g) cap is added to newly transcribed rna polymerase ii (rnap ii) transcripts. a subset of rnap ii-transcribed cellular rnas, including small nuclear rna (snrna), small nucleolar rna (snorna), and telomerase rna, is further hypermethylated at the exocyclic n2 of the guanosine to create a trimethylguanosine (tmg)-capp ... | 2010 | 20679221 |
| chikungunya virus nonstructural protein 2 inhibits type i/ii interferon-stimulated jak-stat signaling. | chikungunya virus (chikv) is an emerging human pathogen transmitted by mosquitoes. like that of other alphaviruses, chikv replication causes general host shutoff, leading to severe cytopathicity in mammalian cells, and inhibits the ability of infected cells to respond to interferon (ifn). recent research, however, suggests that alphaviruses may have additional mechanisms to circumvent the host's antiviral ifn response. here we show that chikv replication is resistant to inhibition by interferon ... | 2010 | 20686047 |
| host factors associated with the sindbis virus rna-dependent rna polymerase: role for g3bp1 and g3bp2 in virus replication. | sindbis virus (sinv) is the prototype member of the alphavirus genus, whose members cause severe human diseases for which there is no specific treatment. to ascertain host factors important in the replication of the sinv rna genome, we generated a sinv expressing nsp4, the viral rna-dependent rna polymerase, with an in-frame 3xflag epitope tag. proteomic analysis of nsp4-containing complexes isolated from cells infected with the tagged virus revealed 29 associated host proteins. of these, 10 pro ... | 2010 | 20392851 |
| a recombinant aedna containing the insect-specific toxin, bmk it1, displayed an increasing pathogenicity on aedes albopictus. | the aedes aegypti densovirus (aednv) has previously shown potential in mosquito control. to improve its efficacy as a biopesticide, the gene for an excitatory insect-specific toxin from buthus martensii karsch (bmk it1) was inserted into the aednv genome and cloned into puca plasmid. the coding sequence for green fluorescent protein was ligated to the c-terminus of the bmk it1 gene as a screening marker. recombinant and helper plasmids were cotransfected into c6/36 cells; wild-type viruses were ... | 2010 | 20810829 |
| plk2 attachment to nsf induces homeostatic removal of glua2 during chronic overexcitation. | trafficking of ampa receptors (ampars) is important for many forms of synaptic plasticity. however, the link between activity and resulting synaptic alterations is not fully understood. we identified a direct interaction between n-ethylmaleimide-sensitive fusion protein (nsf), an atpase involved in membrane fusion events and stabilization of surface ampars, and polo-like kinase- 2 (plk2), an activity-inducible kinase that homeostatically decreases excitatory synapse number and strength. plk2 dis ... | 2010 | 20802490 |
| viperin is highly induced in neutrophils and macrophages during acute and chronic lymphocytic choriomeningitis virus infection. | although most cells are thought to respond to ifns, there is limited information regarding specific cells that respond in vivo. viperin is an ifn-induced antiviral protein and, therefore, is an excellent marker for ifn-responsive cells. in this study, we analyzed viperin expression in vivo during acute lymphocytic choriomeningitis virus armstrong infection, which induces high levels of type i ifns, and in persistently infected lymphocytic choriomeningitis virus carrier mice, which contain low le ... | 2010 | 20410488 |
| phylogeographic structure and evolutionary history of sindbis virus. | sindbis (sin) virus, alphavirus, is a mosquito-borne and bird-associated virus with large geographic distribution in the old world. we investigated the genetic diversity of 59 sin strains after limited sequencing of their e2 glycoprotein genes. the sin strains showed maximal diversity of 22.2% at the amino acid (aa) level, and formed five tentative genotypes. the sin-i genotype included strains from europe and africa. strains from australia and east asia formed sin-ii and sin-iii with about 12% ... | 2010 | 20420530 |
| comparison of the immune responses induced by chimeric alphavirus-vectored and formalin-inactivated alum-precipitated measles vaccines in mice. | a variety of vaccine platforms are under study for development of new vaccines for measles. problems with past measles vaccines are incompletely understood and underscore the need to understand the types of immune responses induced by different types of vaccines. detailed immune response evaluation is most easily performed in mice. although mice are not susceptible to infection with wild type or vaccine strains of measles virus, they can be used for comparative evaluation of the immune responses ... | 2010 | 20421972 |
| 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 |
| rna 5'-triphosphatase activity of the hepatitis e virus helicase domain. | hepatitis e virus (hev) has a positive-sense rna genome with a 5'-m7g cap. hev open reading frame 1 (orf1) encodes a polyprotein with multiple enzyme domains required for replication. hev helicase is a nucleoside triphosphatase (ntpase) with the ability to unwind rna duplexes in the 5'-to-3' direction. when incubated with 5'-[gamma-(32)p]rna and 5'-[alpha-(32)p]rna, hev helicase released (32)p only from 5'-[gamma-(32)p]rna, showing specificity for the gamma-beta-triphosphate bond. removal of gam ... | 2010 | 20592074 |
| 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 |
| bid regulates the pathogenesis of neurotropic reovirus. | reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (cns). nf-kappab-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to nf-kappab signaling followi ... | 2010 | 20617182 |
| limited interference at the early stage of infection between two recombinant novirhabdoviruses: viral hemorrhagic septicemia virus and infectious hematopoietic necrosis virus. | the genome sequence of a hypervirulent novirhabdovirus, viral hemorrhagic septicemia virus (vhsv) french strain 23-75, was determined. compared to the genome of the prototype fil3 strain, a number of substitutions, deletions, and insertions were observed. following the establishment of a plasmid-based minigenome replication assay, recombinant vhsv (rvhsv) was successfully recovered. rvhsv exhibits wild-type-like growth properties in vitro as well as in vivo in rainbow trout. the dispensable role ... | 2010 | 20631140 |
| substitution of 5-ht1a receptor signaling by a light-activated g protein-coupled receptor. | understanding serotonergic (5-ht) signaling is critical for understanding human physiology, behavior, and neuropsychiatric disease. 5-ht mediates its actions via ionotropic and metabotropic 5-ht receptors. the 5-ht(1a) receptor is a metabotropic g protein-coupled receptor linked to the g(i/o) signaling pathway and has been specifically implicated in the pathogenesis of depression and anxiety. to understand and precisely control 5-ht(1a) signaling, we created a light-activated g protein-coupled r ... | 2010 | 20643652 |
| 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 |
| virus-infection or 5'ppp-rna activates antiviral signal through redistribution of ips-1 mediated by mfn1. | in virus-infected cells, rig-i-like receptor (rlr) recognizes cytoplasmic viral rna and triggers innate immune responses including production of type i and iii interferon (ifn) and the subsequent expression of ifn-inducible genes. interferon-beta promoter stimulator 1 (ips-1, also known as mavs, visa and cardif) is a downstream molecule of rlr and is expressed on the outer membrane of mitochondria. while it is known that the location of ips-1 is essential to its function, its underlying mechanis ... | 2010 | 20661427 |
| growth and maintenance of baby hamster kidney (bhk) cells. | the bhk21 cell line was established in 1961 from the kidneys of 5 syrian hamsters from litter number 21. since this time, this cell line has been a laboratory standard for the growth of countless viruses and the study of many biological processes. the specific use for the growth of sindbis virus is described, although it may apply to many types of viruses. | 2010 | 20440683 |
| 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 |
| [effects of the site-directed mutagenesis at nsp2-726pro on replicon vector derived from xj-160 virus]. | to investigate the effects of site-directed mutagenesis at nsp2-726pro on the characteristics of replicon vector derived from xj-160 virus, a sindbis virus (sinv) isolated in china. the mutant vector pbrep-726l, pbrep-726s, pbrep-726v or pbrep-726a was constructed by introducing nsp2-726pro --> leu, nsp2-726pro --> ser, nsp2-726pro --> val or nsp2-726pro --> ala into xj-160 viral replicon vector pbrepxj respectively. to quantitatively and qualitatively determine the site-directed mutagenesis on ... | 2010 | 20480641 |
| 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 |
| semliki forest virus-induced endoplasmic reticulum stress accelerates apoptotic death of mammalian cells. | the alphavirus semliki forest virus (sfv) and its derived vectors induce apoptosis in mammalian cells. here, we show that apoptosis is associated with the loss of mitochondrial membrane potential followed by the activation of caspase-3, caspase-8, and caspase-9. cell death can be partially suppressed by treatment with the pan-caspase inhibitor zvad-fmk. to determine the role of sfv structural proteins in cell death, the temporal course of cell death was compared in cells infected with sfv and ce ... | 2010 | 20427528 |
| 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 |
| redirecting lentiviral vectors pseudotyped with sindbis virus-derived envelope proteins to dc-sign by modification of n-linked glycans of envelope proteins. | redirecting the tropism of viral vectors enables specific transduction of selected cells by direct administration of vectors. we previously developed targeting lentiviral vectors by pseudotyping with modified sindbis virus envelope proteins. these modified sindbis virus envelope proteins have mutations in their original receptor-binding regions to eliminate their natural tropisms, and they are conjugated with targeting proteins, including antibodies and peptides, to confer their tropisms on targ ... | 2010 | 20484510 |
| 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 |
| in vitro and in vivo characterization of microrna-targeted alphavirus replicon and helper rnas. | alphavirus-based replicon vector systems (family togaviridae) have been developed as expression vectors with demonstrated potential in vaccine development against both infectious diseases and cancer. the single-cycle nature of virus-like replicon particles (vrp), generated by supplying the structural proteins from separate replicable helper rnas, is an attractive safety component of these systems. micrornas (mirnas) have emerged as important cellular rna regulation elements. recently, mirnas hav ... | 2010 | 20504925 |
| 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 |
| membrane uncoating of intact enveloped viruses. | experiments in the 1960s showed that sendai virus, a paramyxovirus, fused its membrane with the host plasma membrane. after membrane fusion, the virus spontaneously "uncoated" with diffusion of the viral membrane proteins into the host plasma membrane and a merging of the host and viral membranes. this led to deposit of the viral ribonucleoprotein (rnp) and interior proteins in the cell cytoplasm. later work showed that the common procedure then used to grow sendai virus produced damaged, pleomo ... | 2010 | 20668081 |
| plasma membrane insertion of the ampa receptor glua2 subunit is regulated by nsf binding and q/r editing of the ion pore. | the delivery of ampa receptors to the plasma membrane is a critical step both for the synaptic delivery of these receptors and for the regulation of synaptic transmission. to directly visualize fusion events of transport vesicles containing the ampa receptor glua2 subunit with the plasma membrane we used phluorin-tagged glua2 subunits and total internal reflection fluorescence microscopy. we demonstrate that the plasma membrane insertion of glua2 requires the nsf binding site within its intracel ... | 2010 | 20534470 |
| infection, dissemination, and transmission of a west nile virus green fluorescent protein infectious clone by culex pipiens quinquefasciatus mosquitoes. | we report the construction and comparative characterization of a full-length west nile virus (wnv) cdna infectious clone (ic) that contains a green fluorescent protein (gfp) expression cassette fused within the viral open reading frame. virus derived from wnv-gfp ic stably infected culex pipiens quinquefasciatus mosquitoes at comparable rates to virus derived from the parental (non-gfp) ic. however, insertion of this gfp cassette resulted in a temporal delay in in vivo replication kinetics and s ... | 2010 | 19619041 |
| multiple functions of the 37/67-kd laminin receptor make it a suitable target for novel cancer gene therapy. | the 37/67-kd laminin receptor, lamr, is a multifunctional protein that associates with the 40s ribosomal subunit and also localizes to the cell membrane to interact with the extracellular matrix. lamr is overexpressed in many types of cancer, playing important roles in tumor-cell migration and invasion. here, we show that lamr is also vital for tumor-cell proliferation, survival, and protein translation. small-interfering rna (sirna)-mediated reduction in expression of lamr leads to g1 phase cel ... | 2010 | 19724263 |
| larval environmental temperature and the susceptibility of aedes albopictus skuse (diptera: culicidae) to chikungunya virus. | a key feature in the recent widespread epidemic of the mosquito-borne alphavirus chikungunya virus (chikv) was the important role of aedes albopictus, formerly regarded as a secondary vector, compared to the presumed primary vector aedes aegypti. ae. albopictus, a container-inhabiting mosquito, is an invasive species that occurs over a wide geographic range spanning tropical and temperate latitudes. in this study we examine the effects of a broad range of larval rearing temperatures on chikv inf ... | 2010 | 19725768 |
| transgenesis and paratransgenesis to control insect-borne diseases: current status and future challenges. | insect-borne diseases cause significant human morbidity and mortality. current control and preventive methods against vector-borne diseases rely mainly on insecticides. the emergence of insecticide resistance in many disease vectors highlights the necessity to develop new strategies to control these insects. vector transgenesis and paratransgenesis are novel strategies that aim at reducing insect vectorial capacity, or seek to eliminate transmission of pathogens such as plasmodium sp., trypanoso ... | 2010 | 19819346 |
| a trans-complementing recombination trap demonstrates a low propensity of flaviviruses for intermolecular recombination. | intermolecular recombination between the genomes of closely related rna viruses can result in the emergence of novel strains with altered pathogenic potential and antigenicity. although recombination between flavivirus genomes has never been demonstrated experimentally, the potential risk of generating undesirable recombinants has nevertheless been a matter of concern and controversy with respect to the development of live flavivirus vaccines. as an experimental system for investigating the abil ... | 2010 | 19864381 |
| viral mutagenesis as a means for generating novel proteins. | we demonstrate that a mutation-prone virus engineered to express a foreign gene is an expedient means for generating novel mutant nonviral proteins in mammalian cells. using vesicular stomatitis virus to express a gene coding for a fluorescent dsred protein, a number of green mutant variants including a new variant not previously described were rapidly isolated from infected cells, sequenced, and cloned. similar methods may be useful in the development of physiologically sensitive fluorescent re ... | 2010 | 19906913 |
| identification of gbf1 as a cellular factor required for hepatitis c virus rna replication. | in infected cells, hepatitis c virus (hcv) induces the formation of membrane alterations referred to as membranous webs, which are sites of rna replication. in addition, hcv rna replication also occurs in smaller membrane structures that are associated with the endoplasmic reticulum. however, cellular mechanisms involved in the formation of hcv replication complexes remain largely unknown. here, we used brefeldin a (bfa) to investigate cellular mechanisms involved in hcv infection. bfa acts on c ... | 2010 | 19906930 |
| mhv68 complement regulatory protein facilitates mhv68 replication in primary macrophages in a complement independent manner. | murine gammaherpesvirus-68 (mhv68) is genetically related to human epstein-barr virus and kaposi's sarcoma-associated herpesvirus and provides a tractable model to study gammaherpesvirus-host interactions in vivo and in vitro. the mhv68-encoded v-rca product inhibits murine complement activation and shares sequence homology with other virus and host regulators of complement activation. here we show that v-rca is required for efficient mhv68 replication in primary murine macrophages, but not in m ... | 2010 | 19910013 |
| host and viral translational mechanisms during cricket paralysis virus infection. | the dicistrovirus is a positive-strand single-stranded rna virus that possesses two internal ribosome entry sites (ires) that direct translation of distinct open reading frames encoding the viral structural and nonstructural proteins. through an unusual mechanism, the intergenic region (igr) ires responsible for viral structural protein expression mimics a trna to directly recruit the ribosome and set the ribosome into translational elongation. in this study, we explored the mechanism of host tr ... | 2010 | 19889774 |
| skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. | sarcopenia, loss of muscle mass and function, is a common feature of aging. oxidative damage and apoptosis are likely underlying factors. autophagy, a process for the degradation of cellular constituents, may be a mechanism to combat cell damage and death. we investigated the effect of age on autophagy and apoptosis in plantaris muscle of male fischer 344 rats that were either fed ad libitum, or mild, life-long calorie restricted (cr) alone or combined with life-long voluntary exercise. upstream ... | 2010 | 19903516 |
| identification of western equine encephalitis virus structural proteins that confer protection after dna vaccination. | dna vaccines encoding different portions of the structural proteins of western equine encephalitis virus were tested for the efficacy of their protection in a 100% lethal mouse model of the virus. the 6k-e1 structural protein encoded by the dna vaccine conferred complete protection against challenge with the homologous strain and limited protection against challenge with a heterologous strain. | 2010 | 19923571 |
| coronavirus nucleocapsid protein facilitates template switching and is required for efficient transcription. | purified nucleocapsid protein (n protein) from transmissible gastroenteritis virus (tgev) enhanced hammerhead ribozyme self-cleavage and favored nucleic acid annealing, properties that define rna chaperones, as previously reported. several tgev n-protein deletion mutants were expressed in escherichia coli and purified, and their rna binding ability and rna chaperone activity were evaluated. the smallest n-protein domain analyzed with rna chaperone activity, facilitating dna and rna annealing, co ... | 2010 | 19955314 |
| diagnosis of chikungunya fever in an indian population by an indirect enzyme-linked immunosorbent assay protocol based on an antigen detection assay: a prospective cohort study. | a chikungunya virus (chikv) outbreak continues in india. monitoring of the clinical features of chikv infection is an important component of assessing the disease process. diagnosis is usually made by an immunoglobulin m (igm)/igg enzyme-linked immunosorbent assay (elisa). however, these assays have extremely low sensitivities for the detection of infection in the majority of chikv patients during the acute stage of infection (during the 1 to 4 days after infection). in our laboratory, a sensiti ... | 2010 | 20007365 |
| novel functions of the alphavirus nonstructural protein nsp3 c-terminal region. | the functions of the alphavirus-encoded nonstructural protein nsp3 during infection are poorly understood. in contrast, nsp1, nsp2, and nsp4 have known enzymatic activities and functions. a functional analysis of the c-terminal region of nsp3 of semliki forest virus revealed the presence of a degradation signal that overlaps with a sequence element located between nsp3 and nsp4 that is required for proteolytic processing. this element was responsible for the short half-life (1 h) of individually ... | 2010 | 20015978 |
| acyclic nucleoside phosphonates with 5-azacytosine base moiety substituted in c-6 position. | two methods for preparation of 6-substituted derivatives of anti dna-viral agent 1-(s)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (hpmp-5-azac) were developed: (1) ammonia mediated ring-opening reaction of diisopropyl esters of hpmp-5-azac (4) to carbamoylguanidine derivatives followed by ring-closure reaction with orthoesters and (2) condensation reaction of 6-substituted 5-azacytosines with diisopropyl (1s)-[2-hydroxy-1-tosyloxymethyl)ethoxy]methylphosphonate (15). deprotection of di ... | 2010 | 19914075 |
| 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 |
| 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 |
| 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 |
| 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 |
| encephalitic alphaviruses. | this review will cover zoonotic, encephalitic alphaviruses in the family togaviridae. encephalitic alphaviruses, i.e. western- (weev), eastern- (eeev), venezuelan equine encephalitis virus (veev) and, more rarely, ross river virus, chikungunya virus and highlands j virus (hjv), are neuroinvasive and may cause neurological symptoms ranging from mild (e.g., febrile illness) to severe (e.g., encephalitis) in humans and equines. among the naturally occurring alphaviruses, weev, eeev and veev have wi ... | 2010 | 19775836 |
| 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 |
| 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 |
| enhanced specific delivery and targeting of oncolytic sindbis viral vectors by modulating vascular leakiness in tumor. | genetic instability of cancer cells generates resistance after initial responses to chemotherapeutic agents. several oncolytic viruses have been designed to exploit specific signatures of cancer cells, such as important surface markers or pivotal signaling pathways for selective replication. it is less likely for cancer cells to develop resistance given that mutations in these cancer signatures would negatively impact tumor growth and survival. however, as oncolytic viral vectors are large parti ... | 2010 | 19798121 |
| a virus-like particle vaccine for epidemic chikungunya virus protects nonhuman primates against infection. | chikungunya virus (chikv) has infected millions of people in africa, europe and asia since this alphavirus reemerged from kenya in 2004. the severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. here, we describe a new vaccine that protects against chikv infection of nonhuman primates. we show that selective expression of viral structural proteins gives rise to virus-like particles (vlps) in vitro t ... | 2010 | 20111039 |
| perspectives for preventive and therapeutic hpv vaccines. | human papillomavirus (hpv) has been associated with several human cancers, including cervical cancer, vulvar cancer, vaginal and anal cancer, and a subset of head and neck cancers. thus effective vaccination against hpv provides an opportunity to reduce the morbidity and mortality associated with hpv. the food and drug administration of the united states has approved two preventive vaccines to limit the spread of hpv. however, these are unlikely to impact upon hpv prevalence and cervical cancer ... | 2010 | 20123582 |
| type i ifn controls chikungunya virus via its action on nonhematopoietic cells. | chikungunya virus (chikv) is the causative agent of an outbreak that began in la réunion in 2005 and remains a major public health concern in india, southeast asia, and southern europe. chikv is transmitted to humans by mosquitoes and the associated disease is characterized by fever, myalgia, arthralgia, and rash. as viral load in infected patients declines before the appearance of neutralizing antibodies, we studied the role of type i interferon (ifn) in chikv pathogenesis. based on human studi ... | 2010 | 20123960 |
| egg-independent vaccine strategies for highly pathogenic h5n1 influenza viruses. | the emergence of a highly pathogenic h5n1 influenza virus in hong kong in 1997 and the subsequent appearance of other h5n1 strains and their spread to several countries in southeast asia, africa, the middle east and europe has evoked fear of a global influenza pandemic. vaccines offer the best hope to combat the threat of an influenza pandemic. however, the global demand for a pandemic vaccine cannot be fulfilled by the current egg-based vaccine manufacturing strategies, thus creating a need to ... | 2010 | 19875936 |
| 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 |
| pro-inflammatory response resulting from sindbis virus infection of human macrophages: implications for the pathogenesis of viral arthritis. | several viruses cause acute and chronic joint inflammation in humans, and among them, the alphaviruses are of special interest due to the increasing number of outbreaks in which they are the etiological factor. sindbis virus (sinv), a member of the alphavirus genus, is the most widely distributed of all known arboviruses. although sinv causes arthritis in humans, the molecular and cellular factors that contribute to the pathogenesis of this disease are almost completely unknown. despite the cruc ... | 2010 | 19950249 |
| 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 |
| targeting lentiviral vector to specific cell types through surface displayed single chain antibody and fusogenic molecule. | viral delivery remains one of the most commonly used techniques today in the field of gene therapy. however, one of the remaining hurdles is the off-targeting effect of viral delivery. to overcome this obstacle, we recently developed a method to incorporate an antibody and a fusogenic molecule (fm) as two distinct molecules into the lentiviral surface. in this report, we expand this strategy to utilize a single chain antibody (scab) for targeted transduction. | 2010 | 20149250 |
| sindbis viral vector induced apoptosis requires translational inhibition and signaling through mcl-1 and bak. | sindbis viral vectors are able to efficiently target and kill tumor cells in vivo, as shown using pancreatic and ovarian cancer models. infection results in apoptosis both in vitro and in vivo. sindbis vector uptake is mediated by the lamr, which is upregulated on a number of different tumor types, thus conferring specificity of the vector to a wide range of cancers. in this study we elucidate the mechanism of apoptosis in two tumor cell lines, mosec, derived from the ovarian epithelium and pan0 ... | 2010 | 20152035 |
| gene expression in the brain during reovirus encephalitis. | viral encephalitis remains a significant cause of morbidity and mortality throughout the world. we performed microarray analysis to identify genes and pathways that are differentially regulated during reovirus encephalitis and that may provide novel therapeutic targets for virus-induced diseases of the central nervous system (cns). an increase in the expression of 130 cellular genes was found in the brains of reovirus-infected mice at early times post infection, compared to mock-infected control ... | 2010 | 20158406 |
| infection with strains of citrus tristeza virus does not exclude superinfection by other strains of the virus. | superinfection exclusion or homologous interference, a phenomenon in which a primary viral infection prevents a secondary infection with the same or closely related virus, has been observed commonly for viruses in various systems, including viruses of bacteria, plants, and animals. with plant viruses, homologous interference initially was used as a test of virus relatedness to define whether two virus isolates were "strains" of the same virus or represented different viruses, and subsequently pu ... | 2010 | 19923189 |
| autophagy protects against sindbis virus infection of the central nervous system. | autophagy functions in antiviral immunity. however, the ability of endogenous autophagy genes to protect against viral disease in vertebrates remains to be causally established. here, we report that the autophagy gene atg5 function is critical for protection against lethal sindbis virus (sin) infection of the mouse central nervous system. inactivating atg5 in sin-infected neurons results in delayed clearance of viral proteins, increased accumulation of the cellular p62 adaptor protein, and incre ... | 2010 | 20159618 |
| autophagy evasion in herpesviral latency. | autophagy constitutes a major catabolic process for the quality control of internal proteins and organelles of eukaryotic cells, and is emerging as an essential part of the host antiviral defense. many studies have shed light on the importance of autophagy in homeostasis, but it is not well understood how viruses co-opt the cellular autophagic pathway to establish virulence in vivo. our recent study presents direct in vivo evidence for the key role of the anti-autophagic aspect of the virally en ... | 2010 | 19923915 |
| pip3 controls synaptic function by maintaining ampa receptor clustering at the postsynaptic membrane. | despite their low abundance, phosphoinositides are critical regulators of intracellular signaling and membrane compartmentalization. however, little is known of phosphoinositide function at the postsynaptic membrane. here we show that continuous synthesis and availability of phosphatidylinositol-(3,4,5)-trisphosphate (pip(3)) at the postsynaptic terminal is necessary for sustaining synaptic function in rat hippocampal neurons. this requirement was specific for synaptic, but not extrasynaptic, am ... | 2010 | 20010819 |
| neurons preferentially respond to self-mhc class i allele products regardless of peptide presented. | studies of mice lacking mhc class i (mhc i)-associated proteins have demonstrated a role for mhc i in neurodevelopment. a central question arising from these observations is whether neuronal recognition of mhc i has specificity for the mhc i allele product and the peptide presented. using a well-established embryonic retina explant system, we observed that picomolar levels of a recombinant self-mhc i molecule inhibited neurite outgrowth. we then assessed the neurobiological activity of a panel o ... | 2010 | 20018625 |
| viral pathogenesis in mice is similar for west nile virus derived from mosquito and mammalian cells. | west nile virus (wnv) is a mosquito-borne pathogen. during replication, wnv acquires different carbohydrates and lipid membranes, depending on its mosquito or vertebrate hosts. consequently, wnv derived from mosquito and vertebrate cell lines differ in their infectivity for dendritic cells (dcs) and induction of type i interferon (ifn-alpha/beta) in vitro. we evaluated the pathogenesis of wnv derived from mosquito (wnv(c6/36)) and vertebrate (wnv(bhk)) cell lines in mice. the tissue tropism, inf ... | 2010 | 20167345 |
| initiation of duck hepatitis b virus infection requires cleavage by a furin-like protease. | the entry mechanism of hepatitis b virus (hbv) has not been defined, and this impedes development of antiviral therapies aimed at an early step in the viral life cycle. hbv infection has both host and tissue specificities. for the related duck hepatitis b virus (dhbv), duck carboxypeptidase d (dcpd) has been proposed as the species-specific docking receptor, while glycine decarboxylase (dgd) may serve as a tissue-specific cofactor or secondary receptor. dgd binds to several truncated versions of ... | 2010 | 20181690 |