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immunotherapy for cervical cancer: research status and clinical potential.the high-risk types of human papillomavirus (hpv) have been found to be associated with most cervical cancers and play an essential role in the pathogenesis of the disease. despite recent advances in preventive hpv vaccine development, such preventive vaccines are unlikely to reduce the prevalence of hpv infections within the next few years, due to their cost and limited availability in developing countries. furthermore, preventive hpv vaccines may not be capable of treating established hpv infe ...201020199126
the vpu protein: new concepts in virus release and cd4 down-modulation.human immunodeficiency virus type 1 (hiv-1) and several simian immunodeficiency viruses (siv) encode for a transmembrane protein known as vpu (viral protein u). while one of the smallest of the hiv-1 proteins, it has two important functions within virus-infected cells. the first of these functions is the down-regulation of the cd4 receptor to prevent its interaction with the hiv-1 envelope glycoprotein. vpu interacts with the cd4 receptor in the rough endoplasmic reticulum (rer), resulting in it ...201020201792
translation control by protein kinase r restricts minute virus of mice infection: role in parvovirus oncolysis.the relevance of translational control in the gene expression and oncotropism of the autonomous parvoviruses was investigated with mvmp, the prototype strain of minute virus of mice (mvm), infecting normal and transformed rodent and human cells of different tissue origins. mouse embryo fibroblasts (mefs) and nih 3t3 fibroblasts were resistant to mvmp infection, but 3t3 fibroblasts derived from double-stranded rna (dsrna)-dependent protein kinase r (pkr) knockout mice (pkr(o/o)) behaved in a mann ...201020219905
the structure of sindbis virus produced from vertebrate and invertebrate hosts as determined by small-angle neutron scattering.the complex natural cycle of vectored viruses that transition between host species, such as between insects and mammals, makes understanding the full life cycle of the virus an incredibly complex problem. sindbis virus, an arbovirus and prototypic alphavirus having an inner protein shell and an outer glycoprotein coat separated by a lipid membrane, is one example of a vectored virus that transitions between vertebrate and insect hosts. while evidence of host-specific differences in sindbis virus ...201020219936
synthesis, antiviral activity and cytotoxicity evaluation of schiff bases of some 2-phenyl quinazoline-4(3)h-ones.a new series of 3-(benzylideneamino)-2-phenylquinazoline-4(3h)-ones were prepared through schiff base formation of 3-amino-2-phenyl quinazoline-4(3)h-one with various substituted carbonyl compounds. their chemical structures were elucidated by spectral studies. cytotoxicity and antiviral activity were evaluated against herpes simplex virus-1 (kos), herpes simplex virus-2 (g), vaccinia virus, vesicular stomatitis virus, herpes simplex virus-1 tk- kos acvr, para influenza-3 virus, reovirus-1, sind ...201020724039
regression of human prostate tumors and metastases in nude mice following treatment with the recombinant oncolytic vaccinia virus glv-1h68.virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. in the current study, we analyzed the therapeutic efficacy of the oncolytic vaccinia virus glv-1h68 against two human prostate cancer cell lines du-145 and pc-3 in cell culture and in tumor xenograft models. by viral proliferation assays and cell survival tests, we demonstrated that glv-1h68 was able to infect, replicate in, and lyse these prostate cancer cells in culture. in du-145 ...201020379368
cotton rats and house sparrows as hosts for north and south american strains of eastern equine encephalitis virus.eastern equine encephalitis virus (eeev; family togaviridae, genus alphavirus) is an arbovirus that causes severe disease in humans in north america and in equids throughout the americas. the enzootic transmission cycle of eeev in north america involves passerine birds and the ornithophilic mosquito vector, culiseta melanura, in freshwater swamp habitats. however, the ecology of eeev in south america is not well understood. culex (melanoconion) spp. mosquitoes are considered the principal vector ...201020735920
advances in the field of lentivector-based transduction of t and b lymphocytes for gene therapy.efficient gene transfer into quiescent t and b lymphocytes for gene therapy or immunotherapy purposes may allow the treatment of several genetic dysfunctions of the hematopoietic system, such as immunodeficiencies, and the development of novel therapeutic strategies for cancers and acquired diseases. lentiviral vectors (lvs) can transduce many types of nonproliferating cells, with the exception of some particular quiescent cell types such as resting t and b cells. in t cells, completion of rever ...201020736930
a determinant of sindbis virus neurovirulence enables efficient disruption of jak/stat signaling.previous studies with venezuelan equine encephalitis virus and sindbis virus (sinv) indicate that alphaviruses are capable of suppressing the cellular response to type i and type ii interferons (ifns) by disrupting jak/stat signaling; however, the relevance of this signaling inhibition toward pathogenesis has not been investigated. the relative abilities of neurovirulent and nonneurovirulent sinv strains to downregulate jak/stat signaling were compared to determine whether the ability to inhibit ...201020739538
an rna pseudoknot is required for production of yellow fever virus subgenomic rna by the host nuclease xrn1.cells and mice infected with arthropod-borne flaviviruses produce a small subgenomic rna that is colinear with the distal part of the viral 3'-untranslated region (utr). this small subgenomic flavivirus rna (sfrna) results from the incomplete degradation of the viral genome by the host 5'-3' exonuclease xrn1. production of the sfrna is important for the pathogenicity of the virus. this study not only presents a detailed description of the yellow fever virus (yfv) sfrna but, more importantly, des ...201020739539
lc3a-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.autophagy is a self-degradation mechanism by which cells recycle their own cytoplasmic constituents and dispose of excess or defective organelles after starvation and oxygen deprivation. an antibody to the microtubule-associated protein 1 light chain 3 (lc3a), recognizing both the soluble (lc3a-i) and the membrane-bound form (lc3a-ii) of the protein, was used to detect autophagic activity in 102 breast carcinomas. three distinct patterns were recognized: (1) diffuse cytoplasmic, (2) cytoplasmic/ ...201020382705
calciomics: prediction and analysis of ef-hand calcium binding proteins by protein engineering.ca(2+) plays a pivotal role in the physiology and biochemistry of prokaryotic and mammalian organisms. viruses also utilize the universal ca(2+) signal to create a specific cellular environment to achieve coexistence with the host, and to propagate. in this paper we first describe our development of a grafting approach to understand site-specific ca(2+) binding properties of ef-hand proteins with a helix-loop-helix ca(2+) binding motif, then summarize our prediction and identification of ef-hand ...201020802784
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 ...201020810829
species-specific antagonism of host isgylation by the influenza b virus ns1 protein.interferon-stimulated expression and conjugation of the ubiquitin-like modifier isg15 restricts replication of several viruses. here, we established complete e1-activating, e2-conjugating, and e3 ligase-dependent expression systems for assaying both human and mouse isgylation. we confirm that human herc5, but not human herc6, has isg15 e3 ligase activity and identify mouse herc6 as a bona fide isg15 e3 ligase. furthermore, we demonstrate that influenza b virus ns1 protein potently antagonizes hu ...201020219937
functional sindbis virus replicative complexes are formed at the plasma membrane.formation of virus-specific replicative complexes (rcs) in infected cells is one of the most intriguing and important processes that determine virus replication and ultimately their pathogenesis on the molecular and cellular levels. alphavirus replication was known to lead to formation of so-called type 1 cytopathic vacuoles (cpv1s), whose distinguishing feature is the presence of numerous membrane invaginations (spherules) and accumulation of viral nonstructural proteins (nsps) at the cytoplasm ...201020826696
human traf3 adaptor molecule deficiency leads to impaired toll-like receptor 3 response and susceptibility to herpes simplex encephalitis.tumor necrosis factor (tnf) receptor-associated factor 3 (traf3) functions downstream of multiple tnf receptors and receptors that induce interferon-α (ifn-α), ifn-β, and ifn-λ production, including toll-like receptor 3 (tlr3), which is deficient in some patients with herpes simplex virus-1 encephalitis (hse). mice lacking traf3 die in the neonatal period, preventing direct investigation of the role of traf3 in immune responses and host defenses in vivo. here, we report autosomal dominant, human ...201020832341
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 ...201020836893
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 ...201020232362
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% ...201020420530
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 ...201020844027
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 ...201020360360
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 ...201020860480
coxsackievirus infection induces autophagy-like vesicles and megaphagosomes in pancreatic acinar cells in vivo.autophagy can play an important part in protecting host cells during virus infection, and several viruses have developed strategies by which to evade or even exploit this homeostatic pathway. tissue culture studies have shown that poliovirus, an enterovirus, modulates autophagy. herein, we report on in vivo studies that evaluate the effects on autophagy of coxsackievirus b3 (cvb3). we show that in pancreatic acinar cells, cvb3 induces the formation of abundant small autophagy-like vesicles and p ...201020861268
development of a new tacaribe arenavirus infection model and its use to explore antiviral activity of a novel aristeromycin analog.a growing number of arenaviruses can cause a devastating viral hemorrhagic fever (vhf) syndrome. they pose a public health threat as emerging viruses and because of their potential use as bioterror agents. all of the highly pathogenic new world arenaviruses (nwa) phylogenetically segregate into clade b and require maximum biosafety containment facilities for their study. tacaribe virus (tcrv) is a nonpathogenic member of clade b that is closely related to the vhf arenaviruses at the amino acid l ...201020862280
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 ...201020085508
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 ...201020887827
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.201020085692
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 ...201020619377
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 ...201020926570
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 ...201020643652
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 ...201020929811
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 ...201020930072
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 ...201020933590
emerging role of isg15 in antiviral immunity.cells express a plethora of interferon-stimulated genes (isgs) in response to viral infection. among these is isg15, a ubiquitin-like protein (ubl) that can be covalently attached to both host and viral proteins. here we review recent advances toward understanding the role and mechanism of isg15 modification in antiviral defense.201020946978
interferon-lambda: a new addition to an old family.the discovery and initial description of the interferon-lambda (ifn-lambda) family in early 2003 opened an exciting new chapter in the field of ifn research. there are 3 ifn-lambda genes that encode 3 distinct but highly related proteins denoted ifn-lambda1, -lambda2, and -lambda3. these proteins are also known as interleukin-29 (il-29), il-28a, and il-28b, respectively. collectively, these 3 cytokines comprise the type iii subset of ifns. they are distinct from both type i and type ii ifns for ...201020712453
dengue virus ensures its fusion in late endosomes using compartment-specific lipids.many enveloped viruses invade cells via endocytosis and use different environmental factors as triggers for virus-endosome fusion that delivers viral genome into cytosol. intriguingly, dengue virus (den), the most prevalent mosquito-borne virus that infects up to 100 million people each year, fuses only in late endosomes, while activation of den protein fusogen glycoprotein e is triggered already at ph characteristic for early endosomes. are there any cofactors that time den fusion to virion ent ...201020949067
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 ...201020950130
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 ...201020957153
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 ...201020962078
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 ...201020975939
activities of ligatin and mct-1/denr in eukaryotic translation initiation and ribosomal recycling.eukaryotic translation initiation begins with ribosomal recruitment of aminoacylated initiator trna (met-trna(met)(i)) by eukaryotic initiation factor eif2. in cooperation with eif3, eif1, and eif1a, met-trna(met)(i)/eif2/gtp binds to 40s subunits yielding 43s preinitiation complexes that attach to the 5'-terminal region of mrnas and then scan to the initiation codon to form 48s initiation complexes with established codon-anticodon base-pairing. stress-activated phosphorylation of eif2alpha redu ...201020713520
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 ...201020976195
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 ...201020802490
r5 hiv env and vesicular stomatitis virus g protein cooperate to mediate fusion to naive cd4+ t cells.naïve cd4(4) t cells are resistant to both hiv r5 env and vesicular stomatitis virus g protein (vsv-g)-mediated fusion. however, viral particles carrying both hiv r5 env and vsv-g infect naïve cells by an unexplained mechanism. we show that vsv-g-pseudotyped virus cannot fuse to unstimulated cells because the viral particles cannot be endocytosed. however, virions carrying both hiv r5 env and vsv-g can fuse because cd4 binding allows viral uptake. our findings reveal a unique mechanism by which ...201020980513
antimicrobial and cytotoxic activities of turbinariaconoides (j.agardh) kuetz.brown alga, turbinariaconoideswas successively extracted with n-hexane, cyclohexane, methanol and ethanol:water (1:1). the extracts were evaluated for antibacterial and antifungal activities by disc diffusion method. minimal inhibitory concentration was determined for active extracts by broth dilution method. the antiviral activity and cytotoxicity of the extracts were tested in human embryonic lung (hel) cells (herpes simplex virus-1, herpes simplex virus-2, vaccinia virus, vesicular stomatitis ...201024381606
central roles of nlrs and inflammasomes in viral infection.the immune response to viral infections is determined by a complex interplay between the pathogen and the host. innate immune cells express a set of cytosolic sensors to detect viral infection. recognition by these sensors induces the production of type i interferons and the assembly of inflammasome complexes that activate caspase-1, leading to production of interleukin-1β (il-1β) and il-18. here, i discuss recent progress in our understanding of the central roles of nod-like receptors (nlrs) an ...201020847744
cobalt complexes as antiviral and antibacterial agents.metal ion complexes are playing an increasing role in the development of antimicrobials. we review here the antimicrobial properties of cobalt coordination complexes in oxidation state 3+. in addition to reviewing the cobalt complexes containing polydentate donor ligands, we also focus on the antimicrobial activity of the homoleptic [co(nh₃)₆](3+) ion.201027713325
autophagy and innate immunity: triggering, targeting and tuning.autophagy is a conserved catabolic stress response pathway that is increasingly recognized as an important component of both innate and acquired immunity to pathogens. the activation of autophagy during infection not only provides cell-autonomous protection through lysosomal degradation of invading pathogens (xenophagy), but also regulates signaling by other innate immune pathways. this review will focus on recent advances in our understanding of three major areas of the interrelationship betwee ...201020403453
ecdysone and the cell cycle: investigations in a mosquito cell line.cell lines provide a tool for investigating basic biological processes that underlie the complex interactions among the tissues and organs of an intact organism. we compare the evolution of insect and mammalian populations as they progress from diploid cell strains to continuous cell lines, and review the history of the well-characterized aedes albopictus mosquito cell line, c7-10. like kc and s3 cells from drosophila melanogaster, c7-10 cells are sensitive to the insect steroid hormone, 20-hydr ...201020303973
bis(monoacylglycero)phosphate and ganglioside gm1 spontaneously form small homogeneous vesicles at specific concentrations.the morphology and size of hydrated lipid dispersions of bis(monoacylglycero)phosphate (bmp) mixed with varying mole percentages of the ganglioside gm1 were investigated by dynamic light scattering (dls) and transmission electron microscopy (tem). electron paramagnetic resonance (epr) spectroscopy of these same mixtures, doped at 0.5 mol% with doxyl labeled lipids, was used to investigate acyl-chain packing. results show that for 20-30% gm1, hydrated bmp:gm1 mixtures spontaneously form small sph ...201020206128
cell-penetrating peptides for antiviral drug development.viral diseases affect hundreds of millions of people worldwide, and the few available drugs to treat these diseases often come with limitations. the key obstacle to the development of new antiviral agents is their delivery into infected cells in vivo. cell-penetrating peptides (cpps) are short peptides that can cross the cellular lipid bilayer with the remarkable capability to shuttle conjugated cargoes into cells. cpps have been successfully utilized to enhance the cellular uptake and intracell ...201027713263
ecological approaches to informing public health policy and risk assessments on emerging vector-borne zoonoses.pathogens associated with vector-borne zoonoses occur in enzootic cycles within nature. they are driven by a combination of vertebrate host and invertebrate vector population dynamics, which in turn respond to changes in environmental stimuli. human involvement in these cycles, and hence the occurrence of human disease, is often to act as incidental host. from a public health perspective our ability to better predict human outbreaks of these diseases and prepare intervention and mitigation strat ...201022460391
expression profiling and comparative analyses of seven midgut serine proteases from the yellow fever mosquito, aedes aegypti.aedes aegypti utilizes blood for energy production, egg maturation and replenishment of maternal reserves. the principle midgut enzymes responsible for bloodmeal digestion are endoproteolytic serine-type proteases within the s1.a subfamily. while there are hundreds of serine protease-like genes in the a. aegypti genome, only five are known to be expressed in the midgut. we describe the cloning, sequencing and expression profiling of seven additional serine proteases and provide a genomic and phy ...201020100490
the role of the pupal determinant broad during embryonic development of a direct-developing insect.metamorphosis is one of the most common, yet dramatic of life history strategies. in insects, complete metamorphosis with morphologically distinct larval stages arose from hemimetabolous ancestors that were more direct developing. over the past century, several ideas have emerged that suggest the holometabolous pupa is developmentally homologous to the embryonic stages of the hemimetabolous ancestor. other theories consider the pupal stage to be a modification of a hemimetabolous nymph. to addre ...201020127251
genome packaging in viruses.genome packaging is a fundamental process in a viral life cycle. many viruses assemble preformed capsids into which the genomic material is subsequently packaged. these viruses use a packaging motor protein that is driven by the hydrolysis of atp to condense the nucleic acids into a confined space. how these motor proteins package viral genomes had been poorly understood until recently, when a few x-ray crystal structures and cryo-electron microscopy (cryo-em) structures became available. here w ...201020060706
signaling pathways in mitochondrial dysfunction and aging.mitochondria are central players in the determination of cell life and death. they are essential for energy production, since most cellular atp is produced in their matrix by the oxidative phosphorylation pathway. at the same time, mitochondria are the main regulators of apoptotic cell death, mediating both extrinsic (cell-surface receptor mediated) and intrinsic apoptotic pathways. reactive oxygen species (ros) accumulate as side products of the electron transport chain, causing mitochondrial d ...201020655326
lack of evidence for the presence of mosquito-borne arboviruses in the upper rhine valley, germany, in 1999 to 2000. 201020592140
autophagy of intracellular microbes and mitochondria: two sides of the same coin?autophagy has become a biological paradigm of how eukaryotic cells, especially those that are long lived, maintain their vitality, control the quality of cytoplasmic organelles, and stay alive or die when growth factors are withdrawn and there is an energy or nutrient crisis. the role of autophagy has been extended to innate and adaptive immunity functions, which surpassed all initial expectations in terms of how immunity and autophagy are interconnected. of particular interest at the moment is ...201020948788
viral hijacking of the host ubiquitin system to evade interferon responses.the post-translational attachment of ubiquitin or ubiquitin-like modifiers (ulms) to proteins regulates many cellular processes including the generation of innate and adaptive immune responses to pathogens. vice versa, pathogens counteract immune defense by inhibiting or redirecting the ubiquitination machinery of the host. a common immune evasion strategy is for viruses to target host immunoproteins for proteasomal or lysosomal degradation by employing viral or host ubiquitin ligases. by degrad ...201020699190
mammalian cell transfection: the present and the future.transfection is a powerful analytical tool enabling study of the function of genes and gene products in cells. the transfection methods are broadly classified into three groups; biological, chemical, and physical. these methods have advanced to make it possible to deliver nucleic acids to specific subcellular regions of cells by use of a precisely controlled laser-microscope system. the combination of point-directed transfection and mrna transfection is a new way of studying the function of gene ...201020549496
intrinsic cellular defenses against virus infection by antiviral type i interferon.intrinsic cellular defenses are non-specific antiviral activities by recognizing pathogen-associated molecular patterns (pamps). toll-like receptors (tlrs), one of the pathogen recognize receptor (prr), sense various microbial ligands. especially, tlr2, tlr3, tlr4, tlr7, tlr8 and tlr9 recognize viral ligands such as glycoprotein, single- or double-stranded rna and cpg nucleotides. the binding of viral ligands to tlrs transmits its signal to toll/interleukin-1 receptor (tir) to activate transcrip ...200920046508
distance-dependent homeostatic synaptic scaling mediated by a-type potassium channels.many lines of evidence suggest that the efficacy of synapses on ca1 pyramidal neuron dendrites increases as a function of distance from the cell body. the strength of an individual synapse is also dynamically modulated by activity-dependent synaptic plasticity, which raises the question as to how a neuron can reconcile individual synaptic changes with the maintenance of the proximal-to-distal gradient of synaptic strength along the dendrites. as the density of a-type potassium channels exhibits ...200920076774
calreticulin: non-endoplasmic reticulum functions in physiology and disease.calreticulin (crt), when localized to the endoplasmic reticulum (er), has important functions in directing proper conformation of proteins and glycoproteins, as well as in homeostatic control of cytosolic and er calcium levels. there is also steadily accumulating evidence for diverse roles for crt localized outside the er, including data suggesting important roles for crt localized to the outer cell surface of a variety of cell types, in the cytosol, and in the extracellular matrix (ecm). furthe ...200919940256
susceptibility of colorectal cancer cells to sindbis virus infection.sindbis virus (sin), a member of the togaviridae family, infects a broad range of cells and has been shown to be an effective anti-tumor agent. the infection efficiency of the virus, however, varies greatly among target cells. in this report, we compared the ability of sin to infect colorectal cancer cells and cells of other cancer origin. while tumor cells from breast, leukemia, and prostate cancers were largely resistant to sin infection, nine of the ten colorectal cancer cell lines tested wer ...200920192123
dynamics of biologically active subpopulations of influenza virus: plaque-forming, noninfectious cell-killing, and defective interfering particles.the dynamic changes in the temporal appearance and quantity of a new class of influenza virus, noninfectious cell-killing particles (nickp), were compared to defective interfering particles (dip). after a single high-multiplicity passage in mdck cells of an egg-derived stock that lacked detectable nickp or dip, both classes of particles appeared in large numbers (>5 x 10(8)/ml), and the plaque-forming particle (pfp) titer dropped approximately 60-fold. after two additional serial high-multiplici ...200919494019
murine coronavirus cell type dependent interaction with the type i interferon response.coronaviruses infect many species of animal including humans, causing acute and chronic diseases of many organ systems. murine coronavirus, mouse hepatitis virus (mhv) infection of the mouse, provides animal models for the study of central nervous system disease, including encephalitis and demyelinating diseases such as multiple sclerosis and for hepatitis. while there are many studies of the adaptive immune response to mhv, there has until recently been scant information on the type i interfero ...200920221421
nv-128, a novel isoflavone derivative, induces caspase-independent cell death through the akt/mammalian target of rapamycin pathway.resistance to apoptosis is 1 of the key events that confer chemoresistance and is mediated by the overexpression of antiapoptotic proteins, which inhibit caspase activation. the objective of this study was to evaluate whether the activation of an alternative, caspase-independent cell death pathway could promote death in chemoresistant ovarian cancer cells. the authors report the characterization of nv-128 as an inducer of cell death through a caspase-independent pathway.200919472400
focus on flaviviruses: current and future drug targets.infection by mosquito-borne flaviviruses (family flaviviridae) is increasing in prevalence worldwide. the vast global, social and economic impact due to the morbidity and mortality associated with the diseases caused by these viruses necessitates therapeutic intervention. there is currently no effective clinical treatment for any flaviviral infection. therefore, there is a great need for the identification of novel inhibitors to target the virus life cycle.200920165556
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 ...200919954860
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 ...200919864570
modulation of cellular tropism and innate antiviral response by viral glycans.arthropod-borne viruses (arboviruses) are a significant cause of human and animal disease worldwide. multiple interactions between virus and the host innate immune system ultimately determine the pathogenesis and clinical outcome of the infection. evidence is rapidly emerging that suggests viral glycans play a key role in viral pathogenesis by regulating host cell tropism and interactions with the host innate immune response. glycan-mediated interactions are especially important for arboviruses ...200920375598
engineering fusogenic molecules to achieve targeted transduction of enveloped lentiviral vectors.lentiviral vectors with broad tropism are one of the most promising gene delivery systems capable of efficiently delivering genes of interest into both dividing and non-dividing cells while maintaining long-term transgene expression. however, there are needs for developing lentiviral vectors with the capability to deliver genes to specific cell types, thus reducing the "off-target" effect of gene therapy. in the present study, we investigated the possibility of engineering the fusion-active doma ...200919490632
chimeric alphavirus vaccine candidates protect mice from intranasal challenge with western equine encephalitis virus.we developed two types of chimeric sindbis virus (sinv)/western equine encephalitis virus (weev) alphaviruses to investigate their potential use as live virus vaccines against wee. the first-generation vaccine candidate, sin/co92, was derived from structural protein genes of weev strain co92-1356, and two second-generation candidates were derived from weev strain mcmillan. for both first- and second-generation vaccine candidates, the nonstructural protein genes were derived from sinv strain ar33 ...200919446595
effects of the nsp2-726 pro mutation on infectivity and pathogenesis of sindbis virus derived from a full-length infectious cdna clone.the point mutations at residue 726 pro in the nonstructural gene 2 (nsp2-726p) could make sindbis virus (sinv) replicons lacking the structural protein-coding region less cytopathic and capable of persisting in some vertebrate cell lines. however, the effects of nsp2-726p mutations on characteristics of sinv in the context of genomic-rna are poorly understood. to investigate the effects of point mutations at nsp2-726p on the infectivity and the pathogenesis of sinv, based on the infectious clone ...200919428754
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 ...200919839605
amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with bindarit, an inhibitor of monocyte chemotactic proteins.alphaviruses such as chikungunya virus, sindbis virus, o'nyong-nyong virus, mayaro virus, and ross river virus (rrv), are commonly associated with arthralgias and overt arthritides worldwide. understanding the processes by which arthritogenic viruses cause disease is a prerequisite in the quest for better treatments. in this regard, we have recently established that monocyte/macrophages are mediators of alphavirus-induced arthritis in mice. we hypothesized that chemokines associated with monocyt ...200919644852
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 ...200920107543
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 ...200919793826
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 ...200919793825
interferon-induced isg15 conjugation inhibits influenza a virus gene expression and replication in human cells.the ubiquitin-like isg15 protein, as well as its conjugating enzymes, is induced by type i interferons (ifns). experiments using isg15 knockout (isg15(-/-)) mice established that isg15 and/or its conjugation inhibits the replication of influenza a virus. however, in contrast to the virus inhibition results for mice, the rates of virus replication in isg15(+/+) and isg15(-/-) mouse embryo fibroblasts in tissue culture were similar. here we focus on human tissue culture cells and on the effect of ...200919357168
autophagy is an essential component of drosophila immunity against vesicular stomatitis virus.intrinsic innate immune mechanisms are the first line of defense against pathogens and exist to control infection autonomously in infected cells. here, we showed that autophagy, an intrinsic mechanism that can degrade cytoplasmic components, played a direct antiviral role against the mammalian viral pathogen vesicular stomatitis virus (vsv) in the model organism drosophila. we found that the surface glycoprotein, vsv-g, was likely the pathogen-associated molecular pattern (pamp) that initiated t ...200919362021
rapid, long-term labeling of cells in the developing and adult rodent visual cortex using double-stranded adeno-associated viral vectors.chronic in vivo imaging studies of the brain require a labeling method that is fast, long-lasting, efficient, nontoxic, and cell-type specific. over the last decade, adeno-associated virus (aav) has been used to stably express fluorescent proteins in neurons in vivo. however, aav's main limitation for many studies (such as those of neuronal development) is the necessity of second-strand dna synthesis, which delays peak transgene expression. the development of double-stranded aav (dsaav) vectors ...200919551873
pick1-mediated glutamate receptor subunit 2 (glur2) trafficking contributes to cell death in oxygen/glucose-deprived hippocampal neurons.oxygen and glucose deprivation (ogd) induces delayed cell death in hippocampal ca1 neurons via ca(2+)/zn(2+)-permeable, glur2-lacking ampa receptors (ampars). following ogd, synaptic ampar currents in hippocampal neurons show marked inward rectification and increased sensitivity to channel blockers selective for glur2-lacking ampars. this occurs via two mechanisms: a delayed down-regulation of glur2 mrna expression and a rapid internalization of glur2-containing ampars during the ogd insult, whi ...200919321442
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 ...200920025741
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 ...200919860871
regulation of synaptic structure by ubiquitin c-terminal hydrolase l1.ubiquitin c-terminal hydrolase l1 (uch-l1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. here, we show that uch-l1 functions in maintaining normal synaptic structure in hippocampal neurons. we found that uch-l1 activity is rapidly upregulated by nmda receptor activation, which leads to an increase in the levels of free monomeric ubiquitin. conversely, pharmacological inhibition of uch-l1 signific ...200919535597
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 ...200920006840
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 ...200919924238
signal transduction pathways in liver and the influence of hepatitis c virus infection on their activities.in liver, the most intensively studied transmembrane and intracellular signal transduction pathways are the janus kinase signal transduction pathway, the mitogen-activated protein kinases signal transduction pathway, the transforming growth factor beta signal transduction pathway, the tumor necrosis factor alpha signal transduction pathway and the recently discovered sphingolipid signal transduction pathway. all of them are activated by many different cytokines and growth factors. they regulate ...200919437557
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 ...200919802565
a versatile targeting system with lentiviral vectors bearing the biotin-adaptor peptide.targeted gene transduction in vivo is the ultimate preferred method for gene delivery. we previously developed targeting lentiviral vectors that specifically recognize cell surface molecules with conjugated antibodies and mediate targeted gene transduction both in vitro and in vivo. although effective in some experimental settings, the conjugation of virus with antibodies is mediated by the interaction between protein a and the fc region of antibodies, which is not as stable as covalent conjugat ...200919455593
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 ...200919915722
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 ...200919918062
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 ...200919918118
activity level-dependent synapse-specific ampa receptor trafficking regulates transmission kinetics.central glutamatergic synapses may express ampa-sensitive glutamate receptors (ampa-rs) with distinct gating properties and exhibit different transmission dynamics, which are important for computing various synaptic inputs received at different populations of synapses. however, how glutamatergic synapses acquire ampa-rs with distinct kinetics to influence synaptic integration remains poorly understood. here i report synapse-specific trafficking of distinct ampa-rs in rat cortical layer 4 stellat ...200919439609
apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection.many viruses, including picornaviruses, have the potential to infect the central nervous system (cns) and stimulate a neuroinflammatory immune response, especially in infants and young children. cognitive deficits associated with cns picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a ...200919608874
tumor necrosis factor-alpha modulates glutamate transport in the cns and is a critical determinant of outcome from viral encephalomyelitis.neuroadapted sindbis virus (nsv) is a neuronotropic virus that causes a fulminant encephalomyelitis in susceptible mice due to death of motor neurons in the brain and spinal cord. we and others have found that uninfected motor neurons die in response to nsv infection, at least in part due to disrupted astrocytic glutamate transport, resulting in excitotoxic motor neuron death. here, we examined the mechanisms of astrocyte dysregulation associated with nsv infection. treatment of organotypic slic ...200919368827
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 ...200919890003
comparison of monkeypox viruses pathogenesis in mice by in vivo imaging.monkeypox viruses (mpxv) cause human monkeypox, a zoonotic smallpox-like disease endemic to africa, and are of worldwide public health and biodefense concern. using viruses from the congo (mpxv-2003-congo-358) and west african (mpxv-2003-usa-044) clades, we constructed recombinant viruses that express the luciferase gene (mpxv-congo/luc+and mpxv-usa-luc+) and compared their viral infection in mice by biophotonic imaging. balb/c mice became infected by both mpxv clades, but they recovered and cle ...200919668372
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 ...200919833547
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