| viral strategies for studying the brain, including a replication-restricted self-amplifying delta-g vesicular stomatis virus that rapidly expresses transgenes in brain and can generate a multicolor golgi-like expression. | viruses have substantial value as vehicles for transporting transgenes into neurons. each virus has its own set of attributes for addressing neuroscience-related questions. here we review some of the advantages and limitations of herpes, pseudorabies, rabies, adeno-associated, lentivirus, and others to study the brain. we then explore a novel recombinant vesicular stomatitis virus (dg-vsv) with the g-gene deleted and transgenes engineered into the first position of the rna genome, which replicat ... | 2009 | 19672982 |
| multiple functions of precursor bdnf to cns neurons: negative regulation of neurite growth, spine formation and cell survival. | proneurotrophins and mature neurotrophins elicit opposite effects via the p75 neurotrophin receptor (p75(ntr)) and trk tyrosine kinase receptors, respectively; however the molecular roles of proneurotrophins in the cns are not fully understood. | 2009 | 19674479 |
| [construction and identification of replicon vector derived from an infectious full-length cdna clone of a sindbis virus]. | to construct vector system of xj-160 virus, a sindbis virus isolated in china, recombinant vector pbrepxj together with its helper plasmid pbr-h were derived from xj-160 viral infectious clone pbr-xj160 by overlap-pcr. to quantitatively and qualitatively verify the function of the replicon system, recombinant plasmids psinrep-egfp, pbrepxj-egfp, psinrep-r and pbrepxj-r were constructed by cloning report genes of enhanced green fluorescent protein (egfp) or renilla luciferase (r. luc) into pbrepx ... | 2009 | 19678570 |
| antiviral activity of innate immune protein isg15. | the host innate immune response, including the production of type-i ifn, represents the primary line of defense against invading viral pathogens. of the hundreds of ifn-stimulated genes (isgs) discovered to date, isg15 was one of the first identified and shown to encode a ubiquitin-like protein that functions, in part, as a modifier of protein function. evidence implicating isg15 as an innate immune protein with broad-spectrum antiviral activity continues to accumulate rapidly. this review will ... | 2009 | 19680460 |
| reverse genetics technology for rift valley fever virus: current and future applications for the development of therapeutics and vaccines. | the advent of reverse genetics technology has revolutionized the study of rna viruses, making it possible to manipulate their genomes and evaluate the effects of these changes on their biology and pathogenesis. the fundamental insights gleaned from reverse genetics-based studies over the last several years provide a new momentum for the development of designed therapies for the control and prevention of these viral pathogens. this review summarizes the successes and stumbling blocks in the devel ... | 2009 | 19682499 |
| characterization of chikungunya pseudotyped viruses: identification of refractory cell lines and demonstration of cellular tropism differences mediated by mutations in e1 glycoprotein. | chikungunya virus (chikv) is an alphavirus responsible for a number of large outbreaks. here we describe the efficient incorporation of chikv envelope glycoproteins into lentiviral and rhabdoviral particles. vectors pseudotyped with chikv envelope proteins efficiently transduced many cell types from different species. however, hematopoietic cell types were either partially or completely refractory. a mutation in e1 (a226v) has been linked with expansion of tropism for mosquito species, although ... | 2009 | 19692105 |
| e1 mutants identify a critical region in the trimer interface of the semliki forest virus fusion protein. | the alphavirus semliki forest virus (sfv) uses a membrane fusion reaction to infect host cells. fusion of the virus and cell membranes is triggered by low ph in the endosome and is mediated by the viral membrane protein e1. during fusion, e1 inserts into the target membrane, trimerizes, and refolds into a hairpin conformation. formation of the e1 homotrimer is critical to membrane fusion, but the mechanism of trimerization is not understood. the crystal structure of the postfusion e1 trimer show ... | 2009 | 19692469 |
| reverse genetic characterization of the natural genomic deletion in sars-coronavirus strain frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo. | during the outbreak of sars in 2002/3, a prototype virus was isolated from a patient in frankfurt/germany (strain frankfurt-1). as opposed to all other sars-coronavirus strains, frankfurt-1 has a 45-nucleotide deletion in the transmembrane domain of its orf 7b protein. when over-expressed in hek 293 cells, the full-length protein but not the variant with the deletion caused interferon beta induction and cleavage of procaspase 3. to study the role of orf 7b in the context of virus replication, we ... | 2009 | 19698190 |
| silencing viral microrna as a novel antiviral therapy? | viruses are intracellular parasites that ensure their existence by converting host cells into viral particle producing entities or into hiding places rendering the virus invisible to the host immune system. some viruses may also survive by transforming the infected cell into an immortal tumour cell. micrornas are small non-coding transcripts that function as posttranscriptional regulators of gene expression. viruses encode mirnas that regulate expression of both cellular and viral genes, and con ... | 2009 | 19704916 |
| [epidemic of pogosta disease--once again?]. | pogosta disease, manifesting itself as joint pain and rash, is an infection caused by sindbis virus. this virus circulates in nature and is occasionally transmitted to humans via mosquitoes. the incidence of antibodies to sindbis virus in the finnish population is approx. 5%, whereas in endemic regions of eastern finland it is several times higher in some places. globally, the prevalence of clinical infection is highest in finland, and the disease has emerged into an epidemic every seventh year. ... | 2009 | 19711594 |
| regulation of host translational machinery by african swine fever virus. | african swine fever virus (asfv), like other complex dna viruses, deploys a variety of strategies to evade the host's defence systems, such as inflammatory and immune responses and cell death. here, we analyse the modifications in the translational machinery induced by asfv. during asfv infection, eif4g and eif4e are phosphorylated (ser1108 and ser209, respectively), whereas 4e-bp1 is hyperphosphorylated at early times post infection and hypophosphorylated after 18 h. indeed, a potent increase i ... | 2009 | 19714237 |
| epistatic roles of e2 glycoprotein mutations in adaption of chikungunya virus to aedes albopictus and ae. aegypti mosquitoes. | between 2005 and 2007 chikungunya virus (chikv) caused its largest outbreak/epidemic in documented history. an unusual feature of this epidemic is the involvement of ae. albopictus as a principal vector. previously we have demonstrated that a single mutation e1-a226v significantly changed the ability of the virus to infect and be transmitted by this vector when expressed in the background of well characterized chikv strains lr2006 opy1 and 37997. however, in the current study we demonstrate that ... | 2009 | 19718263 |
| the phthalocyanine prototype derivative alcian blue is the first synthetic agent with selective anti-human immunodeficiency virus activity due to its gp120 glycan-binding potential. | alcian blue (ab), a phthalocyanine derivative, is able to prevent infection by a wide spectrum of human immunodeficiency virus type 1 (hiv-1), hiv-2, and simian immunodeficiency virus strains in various cell types [t cells, (co)receptor-transfected cells, and peripheral blood mononuclear cells]. with the exception of herpes simplex virus, ab is inactive against a broad variety of other (dna and rna) viruses. time-of-addition studies show that ab prevents hiv-1 infection at the virus entry stage, ... | 2009 | 19721061 |
| a structural and functional perspective of alphavirus replication and assembly. | alphaviruses are small, spherical, enveloped, positive-sense ssrna viruses responsible for a considerable number of human and animal diseases. alphavirus members include chikungunya virus, sindbis virus, semliki forest virus, the western, eastern and venezuelan equine encephalitis viruses, and the ross river virus. alphaviruses can cause arthritic diseases and encephalitis in humans and animals and continue to be a worldwide threat. the viruses are transmitted by blood-sucking arthropods, and re ... | 2009 | 19722838 |
| 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 |
| exclusion of west nile virus superinfection through rna replication. | superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. using west nile virus (wnv) as a model, we show that replicating replicons in bhk-21 cells suppress subsequent wnv infection. the wnv replicon also suppresses superinfections of other flaviviruses but not nonflaviviruses. mode-of-action analysis indicates that the exclusion of wnv superinfection occurs at the step of rna synthesis. the continuous culturing of wnv in the replicon- ... | 2009 | 19726510 |
| a novel function of heparan sulfate in the regulation of cell-cell fusion. | despite the important contribution of cell-cell fusion in the development and physiology of eukaryotes, little is known about the mechanisms that regulate this process. our study shows that glycosaminoglycans and more specifically heparan sulfate (hs) expressed on the cell surface and extracellular matrix may act as negative regulator of cell-cell fusion. using herpes simplex virus type-1 as a tool to enhance cell-cell fusion, we demonstrate that the absence of hs expression on the cell surface ... | 2009 | 19726670 |
| replication cycle of chikungunya: a re-emerging arbovirus. | arboviruses (or arthropod-borne viruses), represent a threat for the new century. the 2005-2006 year unprecedented epidemics of chikungunya virus (chikv) in the french reunion island in the indian ocean, followed by several outbreaks in other parts of the world such as india, have attracted the attention of clinicians, scientists, and state authorities about the risks linked to this re-emerging mosquito-borne virus. chikv, which belongs to the alphaviruses genus, was not previously regarded as a ... | 2009 | 19732931 |
| complement modulates pathogenesis and antibody-dependent neutralization of west nile virus infection through a c5-independent mechanism. | although the interactions of complement and viruses have been widely studied, the function of c5 and the membrane attack complex in the context of viral infection or antibody-mediated neutralization remains controversial. using c5-depleted or -deficient human or mouse sera, we show that c5 does not contribute to the antibody-dependent or -independent neutralization of west nile virus (wnv) in cell culture. consistent with this, c5 neither contributed to protection against wnv pathogenesis nor au ... | 2009 | 19744691 |
| homing endonucleases catalyze double-stranded dna breaks and somatic transgene excision in aedes aegypti. | aedes aegypti is a major vector of arthropod-borne viruses such as yellow fever virus and dengue viruses. efforts to discern the function of genes involved in important behaviours, such as vector competence and host seeking through reverse genetics, would greatly benefit from the ability to generate targeted gene disruptions. homing endonucleases are selfish elements which catalyze double-stranded dna (dsdna) breaks in a sequence-specific manner. in this report we demonstrate that the homing end ... | 2009 | 19754740 |
| recombinant sindbis virus vectors designed to express protective antigen of bacillus anthracis protect animals from anthrax and display synergy with ciprofloxacin. | recombinant sindbis viruses were engineered to express alternative forms of the protective antigen (pa) of bacillus anthracis. the recombinant viruses induced pa-specific immunoglobulin g and neutralizing antibodies in swiss webster mice. vaccination with the recombinant viruses induced immunity that offered some protection from a lethal ames strain spore challenge and synergized the protective effects of ciprofloxacin. | 2009 | 19759250 |
| a novel system for the launch of alphavirus rna synthesis reveals a role for the imd pathway in arthropod antiviral response. | alphaviruses are rna viruses transmitted between vertebrate hosts by arthropod vectors, primarily mosquitoes. how arthropods counteract alphaviruses or viruses per se is not very well understood. drosophila melanogaster is a powerful model system for studying innate immunity against bacterial and fungal infections. in this study we report the use of a novel system to analyze replication of sindbis virus (type species of the alphavirus genus) rna following expression of a sindbis virus replicon r ... | 2009 | 19763182 |
| [using real-time pcr to evaluate the effect of viral inactivation by methylene blue with visible light]. | to investigate the feasibility of using real-time pcr to evaluate the effectiveness of sindbis virus inactivation by methylene blue with visible light. sindbis virus was treated by methylene blue with different intensity of visible light and the transcribed cdna was quantified by real-time pcr. residual infectivity of treated virus was tested by cell infection method as parallel control at the same time. the residual infectivity of virus decreased from 6.50 lgtcid50/ml to under the limit of dete ... | 2009 | 19769162 |
| 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 |
| glycoprotein-dependent acidification of vesicular stomatitis virus enhances release of matrix protein. | to study vesicular stomatitis virus (vsv) entry and uncoating, we generated a recombinant vsv encoding a matrix (m) protein containing a c-terminal tetracysteine lumio tag (rvsv-ml) that could be fluorescently labeled using biarsenical compounds. quantitative confocal microscopy showed that there is a transient loss of fluorescence at early times after the initiation of endocytosis of rvsv-ml-green (rvsv-mlg) virions, which did not occur when cells were treated with bafilomycin a1. the reduction ... | 2009 | 19776119 |
| cis-acting rna elements in human and animal plus-strand rna viruses. | the rna genomes of plus-strand rna viruses have the ability to form secondary and higher-order structures that contribute to their stability and to their participation in inter- and intramolecular interactions. those structures that are functionally important are called cis-acting rna elements because their functions cannot be complemented in trans. they can be involved not only in rna/rna interactions but also in binding of viral and cellular proteins during the complex processes of translation ... | 2009 | 19781674 |
| gene gun administration of therapeutic hpv dna vaccination restores the efficacy of prolonged defrosted viral based vaccine. | freshly defrosted vaccines generate promising antitumor immunity by raising both robust cd8 and cd4 responses with a tc1/th1-dominant cytokine profile. however, prolonged (overnight) defrosted sindbis virus-e7/hsp70 priming and vaccinia-e7/hsp70 booster in mouse model only elicited 20% long-term tumor-free survival in comparison with the fresh vaccines. the present study is to search the possible cause of its potency loss, and to evaluate the ability of pcdna-e7/hsp70 dna vaccination via gene gu ... | 2009 | 19781679 |
| characteristics of alpha/beta interferon induction after infection of murine fibroblasts with wild-type and mutant alphaviruses. | we examined the characteristics of interferon alpha/beta (ifn-alpha/beta) induction after alphavirus or control sendai virus (sev) infection of murine fibroblasts (mefs). as expected, sev infection of wild-type (wt) mefs resulted in strong dimerization of irf3 and the production of high levels of ifn-alpha/beta. in contrast, infection of mefs with multiple alphaviruses failed to elicit detectable ifn-alpha/beta. in more detailed studies, sindbis virus (sinv) infection caused dimerization and nuc ... | 2009 | 19782381 |
| novel vaccines to human rabies. | rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in southeast asia and africa. safe and efficacious vaccines are available to prevent rabies. however, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times fo ... | 2009 | 19787033 |
| targeted transduction via cd4 by a lentiviral vector uses a clathrin-mediated entry pathway. | we recently developed a novel targeting sindbis virus envelope pseudotyped lentiviral vector, 2.2zz, which acquires specific transduction capacity by antibody conjugation and binding with specific antigens on the surface of targeted cells. here we characterize the virological properties of this vector by examining its targeting to cd4 antigen. our results show that entry is dependent on cd4 cell surface density and occurs via the clathrin-mediated endocytic pathway. these findings provide insigh ... | 2009 | 19793825 |
| heavily isotype-dependent protective activities of human antibodies against vaccinia virus extracellular virion antigen b5. | antibodies against the extracellular virion (ev or eev) form of vaccinia virus are an important component of protective immunity in animal models and likely contribute to the protection of immunized humans against poxviruses. using fully human monoclonal antibodies (mabs), we now have shown that the protective attributes of the human anti-b5 antibody response to the smallpox vaccine (vaccinia virus) are heavily dependent on effector functions. by switching fc domains of a single mab, we have def ... | 2009 | 19793826 |
| 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 |
| effect of xiap overexpression on sodium butyrate-induced apoptosis in recombinant chinese hamster ovary cells producing erythropoietin. | previously, overexpression of x-linked inhibitor of apoptosis (xiap), which is known to inhibit activities of caspase-3, -7, and -9 in cho-k1 cells offered protection against sindbis virus-induced apoptosis. in this study, the potential role of xiap overexpression in recombinant cho (rcho) cells treated with sodium butyrate (nabu), which can increase the specific productivity, was investigated by establishing erythropoietin (epo)-producing rcho cells with regulated xiap overexpression (epo-off-x ... | 2009 | 19799944 |
| autophagy in immunity against mycobacterium tuberculosis: a model system to dissect immunological roles of autophagy. | the recognition of autophagy as an immune mechanism has been affirmed in recent years. one of the model systems that has helped in the development of our current understanding of how autophagy and more traditional immunity systems cooperate in defense against intracellular pathogens is macrophage infection with mycobacterium tuberculosis. m. tuberculosis is a highly significant human pathogen that latently infects billions of people and causes active disease in millions of patients worldwide. th ... | 2009 | 19802565 |
| autophagy in mammalian antiviral immunity. | autophagy plays diverse roles in cellular adaptation to stress and promotes vital housekeeping functions by recycling unused or damaged organelles and proteins. as an innate immune defense pathway, autophagy also protects against infection with diverse pathogens, including viruses. autophagy combats infections with both rna and dna viruses, and may function by degrading viral components, by promoting the survival of virally infected cells, and/or by activating innate and adaptive immunity. virus ... | 2009 | 19802570 |
| heparan sulfate proteoglycans are required for cellular binding of the hepatitis e virus orf2 capsid protein and for viral infection. | the hepatitis e virus (hev), a nonenveloped rna virus, is the causative agent of hepatitis e. the mode by which hev attaches to and enters into target cells for productive infection remains unidentified. open reading frame 2 (orf2) of hev encodes its major capsid protein, porf2, which is likely to have the determinants for virus attachment and entry. using an approximately 56-kda recombinant porf2 that can self-assemble as virus-like particles, we demonstrated that cell surface heparan sulfate p ... | 2009 | 19812150 |
| viral bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68. | gamma-herpesviruses (gammahvs) have developed an interaction with their hosts wherein they establish a life-long persistent infection and are associated with the onset of various malignancies. one critical virulence factor involved in the persistency of murine gamma-herpesvirus 68 (gammahv68) is the viral homolog of the bcl-2 protein (vbcl-2), which has been implicated to counteract both host apoptotic responses and autophagy pathway. however, the relative significance of the two activities of v ... | 2009 | 19816569 |
| 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 |
| oncolytic virotherapy for oral squamous cell carcinoma using replication-competent viruses. | oncolytic virotherapy utilizes viruses that can selectively destroy cancer cells without harming normal tissues. clinical trials of oncolytic viruses show that most oncolytic agents are well tolerated and safe. the virotherapeutic agents currently in use have limited potency when administered alone; however, combination therapy using virotherapeutic agents and conventional anticancer agents, such as chemotherapeutics, radiation, and gene therapy, exhibits encouraging levels of efficacy. advances ... | 2009 | 19833547 |
| induction of membrane ceramides: a novel strategy to interfere with t lymphocyte cytoskeletal reorganisation in viral immunosuppression. | silencing of t cell activation and function is a highly efficient strategy of immunosuppression induced by pathogens. by promoting formation of membrane microdomains essential for clustering of receptors and signalling platforms in the plasma membrane, ceramides accumulating as a result of membrane sphingomyelin breakdown are not only essential for assembly of signalling complexes and pathogen entry, but also act as signalling modulators, e. g. by regulating relay of phosphatidyl-inositol-3-kina ... | 2009 | 19834551 |
| rift valley fever vaccines. | rift valley fever virus (rvfv), which belongs to the genus phlebovirus, family bunyaviridae, is a negative-stranded rna virus carrying a tripartite rna genome. rvfv is transmitted by mosquitoes and causes large outbreaks among ruminants and humans in africa and the arabian peninsula. human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis or ocular diseases, whereas ruminants experience abortions during outbreak. effective vaccination of both humans a ... | 2009 | 19837291 |
| vaccines for venezuelan equine encephalitis. | arboviruses are capable of causing encephalitis in animals and human population when transmitted by the vector or potentially via infectious aerosol. recent re-emergence of venezuelan equine encephalitis virus (veev) in south america emphasizes the importance of this pathogen to public health and veterinary medicine. despite its importance no antivirals or vaccines against veev are currently available in the usa. here we review some of the older and newer approaches aimed at generating a safe an ... | 2009 | 19837294 |
| matrix protein 2 of influenza a virus blocks autophagosome fusion with lysosomes. | influenza a virus is an important human pathogen causing significant morbidity and mortality every year and threatening the human population with epidemics and pandemics. therefore, it is important to understand the biology of this virus to develop strategies to control its pathogenicity. here, we demonstrate that influenza a virus inhibits macroautophagy, a cellular process known to be manipulated by diverse pathogens. influenza a virus infection causes accumulation of autophagosomes by blockin ... | 2009 | 19837376 |
| betulin-derived compounds as inhibitors of alphavirus replication. | this paper describes inhibition of semliki forest virus (sfv) replication by synthetic derivatives of naturally occurring triterpenoid betulin (1). chemical modifications were made to oh groups at c-3 and c-28 and to the c-20-c-29 double bond. a set of heterocyclic betulin derivatives was also assayed. a free or acetylated oh group at c-3 was identified as an important structural contributor for anti-sfv activity, 3,28-di-o-acetylbetulin (4) being the most potent derivative (ic50 value 9.1 micro ... | 2009 | 19839605 |
| pathogenesis of aerosolized eastern equine encephalitis virus infection in guinea pigs. | mice and guinea pigs were experimentally exposed to aerosols containing regionally-distinct strains (nj1959 or argm) of eastern equine encephalitis virus (eeev) at two exclusive particle size distributions. mice were more susceptible to either strain of aerosolized eeev than were guinea pigs; however, clinical signs indicating encephalitis were more readily observed in the guinea pigs. lower lethality was observed in both species when eeev was presented at the larger aerosol distribution (> 6 mu ... | 2009 | 19852817 |
| characterization of untranslated regions of the salmonid alphavirus 3 (sav3) genome and construction of a sav3 based replicon. | salmonid alphavirus (sav) causes disease in farmed salmonid fish and is divided into different genetic subtypes (sav1-6). here we report the cloning and characterization of the 5'- and 3'- untranslated regions (utr) of a sav3 isolated from atlantic salmon in norway. the sequences of the utrs are very similar to those of sav1 and sav2, but single nucleotide polymorphisms are present, also in the 3' - conserved sequence element (3'-cse). prediction of the rna secondary structure suggested putative ... | 2009 | 19860871 |
| 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 |
| beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of parkinson's and lewy body diseases. | accumulation of the synaptic protein alpha-synuclein (alpha-syn) is a hallmark of parkinson's disease (pd) and lewy body disease (lbd), a heterogeneous group of disorders with dementia and parkinsonism, where alzheimer's disease and pd interact. accumulation of alpha-syn in these patients might be associated with alterations in the autophagy pathway. therefore, we postulate that delivery of beclin 1, a regulator of the autophagy pathway, might constitute a strategy toward developing a therapy fo ... | 2009 | 19864570 |
| 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 |
| 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 |
| transgenic expression of glud1 (glutamate dehydrogenase 1) in neurons: in vivo model of enhanced glutamate release, altered synaptic plasticity, and selective neuronal vulnerability. | the effects of lifelong, moderate excess release of glutamate (glu) in the cns have not been previously characterized. we created a transgenic (tg) mouse model of lifelong excess synaptic glu release in the cns by introducing the gene for glutamate dehydrogenase 1 (glud1) under the control of the neuron-specific enolase promoter. glud1 is, potentially, an important enzyme in the pathway of glu synthesis in nerve terminals. increased levels of glud protein and activity in cns neurons of hemizygou ... | 2009 | 19890003 |
| 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 |
| 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 |
| 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 |
| therapeutic vaccines against human papillomavirus and cervical cancer. | cervical cancer and its precursor intra-epithelial lesions are linked to infection by a subset of so-called "highrisk" human papillomavirus types, which are estimated to infect nearly four hundred million women worldwide. two prophylactic vaccines have been commercialized recently targeting hpv16 and 18, the most prevalent viral types found in cervical cancer, which operate through induction of capsid-specific neutralizing antibodies. however, in patients with persistent infection these vaccines ... | 2009 | 19915722 |
| hiv-1 gag-specific immunity induced by a lentivector-based vaccine directed to dendritic cells. | lentivectors (lvs) have attracted considerable interest for their potential as a vaccine delivery vehicle. in this study, we evaluate in mice a dendritic cell (dc)-directed lv system encoding the gag protein of human immunodeficiency virus (hiv) (lv-gag) as a potential vaccine for inducing an anti-hiv immune response. the dc-directed specificity is achieved through pseudotyping the vector with an engineered sindbis virus glycoprotein capable of selectively binding to the dc-sign protein. a singl ... | 2009 | 19918062 |
| disrupted glutamate transporter expression in the spinal cord with acute flaccid paralysis caused by west nile virus infection. | neuroinvasive west nile virus (wnv) infections may cause acute flaccid paralysis (afp); in fatal cases, anterior horn cell loss is presumed to be caused by direct viral infection. in related animal models, however, glutamate excitotoxicity mediates bystander injury of uninfected anterior horn cells, suggesting additional pathogenic mechanisms. we examined expression of the principal excitatory amino acid transporter (eaat) of astrocytes (i.e. eaat-2 in humans, glutamate transporter 1 in hamsters ... | 2009 | 19918118 |
| 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 |
| 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 |
| 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 |
| experimental passage of st. louis encephalitis virus in vivo in mosquitoes and chickens reveals evolutionarily significant virus characteristics. | st. louis encephalitis virus (slev; flaviviridae, flavivirus) was the major cause of epidemic flaviviral encephalitis in the u.s. prior to the introduction of west nile virus (wnv) in 1999. however, outbreaks of slev have been significantly more limited then wnv in terms of levels of activity and geographic dispersal. one possible explanation for these variable levels of activity is that differences in the potential for each virus to adapt to its host cycle exist. the need for arboviruses to rep ... | 2009 | 19924238 |
| 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 |
| rack1 is involved in beta-amyloid impairment of muscarinic regulation of gabaergic transmission. | rack1 (receptor for activated c-kinase 1), an anchoring protein that shuttles activated pkc to cellular membranes, plays an important role in pkc-mediated signal transduction pathways. a significant loss of rack1 has been found in the brain of aging animals and alzheimer's disease (ad) patients, which implicates the potential involvement of rack1 in altered pkc activation associated with dementia. our previous studies have demonstrated that gabaergic inhibition in prefrontal cortex, which is imp ... | 2009 | 19954860 |
| 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 |
| hepatitis c virus blocks interferon effector function by inducing protein kinase r phosphorylation. | hepatitis c virus (hcv) is a single-stranded rna virus encoding a single polyprotein whose translation is driven by an internal ribosome entry site (ires). hcv infection strongly induces antiviral interferon-stimulated gene (isg) expression in the liver, yet it persists, suggesting that hcv can block isg effector function. we now show that hcv infection triggers phosphorylation and activation of the rna-dependent protein kinase pkr, which inhibits eukaryotic translation initiation factor eif2 al ... | 2009 | 20006840 |
| 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 |
| 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 |
| 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 |
| 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 |
| reducing oyster-associated bacteria levels using supercritical fluid co2 as an agent of warm pasteurization. | an innovative approach to post-harvest processing (php) of oysters is introduced focusing on the effects of supercritical carbon dioxide (scco(2)) on bacterial contaminants trapped in the digestive system of oysters. oysters were exposed to scco(2) under two conditions: (1) 100 bar and 37 degrees c for 30 min and (2) 172 bar and 60 degrees c for 60 min. using fda standard guidelines for food analysis, variations in the aerobic plate count (apc) were assessed. it was established that exposing oys ... | 2010 | 20022650 |
| a targeted spatial-temporal proteomics approach implicates multiple cellular trafficking pathways in human cytomegalovirus virion maturation. | the assembly of infectious virus particles is a complex event. for human cytomegalovirus (hcmv) this process requires the coordinated expression and localization of at least 60 viral proteins that comprise the infectious virion. to gain insight into the mechanisms controlling this process, we identified protein binding partners for two viral proteins, pul99 (also termed pp28) and pul32 (pp150), which are essential for hcmv virion assembly. we utilized hcmv strains expressing pul99 or pul32 carbo ... | 2010 | 20023299 |
| prophylactic and therapeutic activity of fully human monoclonal antibodies directed against influenza a m2 protein. | influenza virus infection is a prevalent disease in humans. antibodies against hemagglutinin have been shown to prevent infection and hence hemagglutinin is the major constituent of current vaccines. antibodies directed against the highly conserved extracellular domain of m2 have also been shown to mediate protection against influenza a infection in various animal models. active vaccination is generally considered the best approach to combat viral diseases. however, passive immunization is an at ... | 2009 | 20025741 |
| 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 |
| the role of nitric oxide in mycobacterial infections. | although tuberculosis poses a significant health threat to the global population, it is a challenge to develop new and effective therapeutic strategies. nitric oxide (no) and inducible no synthase (inos) are important in innate immune responses to various intracellular bacterial infections, including mycobacterial infections. it is generally recognized that reactive nitrogen intermediates play an effective role in host defense mechanisms against tuberculosis. in a murine model of tuberculosis, n ... | 2009 | 20107543 |
| 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 |
| optogenetic dissection of neuronal circuits in zebrafish using viral gene transfer and the tet system. | the conditional expression of transgenes at high levels in sparse and specific populations of neurons is important for high-resolution optogenetic analyses of neuronal circuits. we explored two complementary methods, viral gene delivery and the itet-off system, to express transgenes in the brain of zebrafish. high-level gene expression in neurons was achieved by sindbis and rabies viruses. the tet system produced strong and specific gene expression that could be modulated conveniently by doxycyc ... | 2009 | 20126518 |