Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
|---|
| role of n-linked glycosylation for sindbis virus infection and replication in vertebrate and invertebrate systems. | each sindbis virus (sinv) surface glycoprotein has two sites for n-linked glycosylation (e1 positions 139 and 245 [e1-139 and e1-245] and e2 positions 196 and 318 [e2-196 and e2-318]). studies of sinv strain te12 mutants with each site eliminated identified the locations of carbohydrates by cryo-electron microscopy (s. v. pletnev et al., cell 105:127-136, 2001). in the current study, the effects of altered glycosylation on virion infectivity, growth in cells of vertebrates and invertebrates, hep ... | 2009 | 19297464 |
| death and survival of heterozygous lurcher purkinje cells in vitro. | the differentiation and survival of heterozygous lurcher (+/lc) purkinje cells in vitro was examined as a model system for studying how chronic ionic stress affects neuronal differentiation and survival. the lurcher mutation in the delta2 glutamate receptor (glurdelta2) converts an orphan receptor into a membrane channel that constitutively passes an inward cation current. in the glurdelta2(+/lc) mutant, purkinje cell dendritic differentiation is disrupted and the cells degenerate following the ... | 0 | 19294643 |
| how b cells shape the immune response against mycobacterium tuberculosis. | extensive work illustrating the importance of cellular immune mechanisms for protection against mycobacterium tuberculosis has largely relegated b-cell biology to an afterthought within the tuberculosis (tb) field. however, recent studies have illustrated that b lymphocytes, through a variety of interactions with the cellular immune response, play previously underappreciated roles in shaping host defense against non-viral intracellular pathogens, including m. tuberculosis. work in our laboratory ... | 2009 | 19283721 |
| hepatitis c virus ns2 is a protease stimulated by cofactor domains in ns3. | chronic infection with hepatitis c virus (hcv) affects 130 million people worldwide and is a major cause of liver cirrhosis and liver cancer. after translation of the hcv rna genome into a polyprotein, 2 viral proteases process its non-structural protein (ns) region. while the essential chymotrypsin-like serine protease ns3-4a mediates all cleavages downstream of ns3, the ns2-3 cysteine protease catalyzes a vital cleavage at the ns2/3 site. protease activity of ns2-3 has been described to requir ... | 2009 | 19282477 |
| reovirus activates transforming growth factor beta and bone morphogenetic protein signaling pathways in the central nervous system that contribute to neuronal survival following infection. | viral infections of the central nervous system (cns) are important causes of worldwide morbidity and mortality, and understanding how viruses perturb host cell signaling pathways will facilitate identification of novel antiviral therapies. we now show that reovirus infection activates transforming growth factor beta (tgf-beta) and bone morphogenetic protein (bmp) signaling in a murine model of encephalitis in vivo. tgf-beta receptor i (tgf-beta ri) expression is increased and its downstream sign ... | 2009 | 19279118 |
| the 5'utr-specific mutation in veev tc-83 genome has a strong effect on rna replication and subgenomic rna synthesis, but not on translation of the encoded proteins. | venezuelan equine encephalitis virus (veev) is one of the most pathogenic members of the alphavirus genus in the togaviridae family. viruses in the veev serocomplex continuously circulate in the central and south america. the only currently available attenuated strain veev tc-83 is being used only for vaccination of at-risk laboratory workers and military personnel. its attenuated phenotype was shown to rely only on two point mutations, one of which, g3a, was found in the 5' untranslated region ... | 2009 | 19278709 |
| adoptive transfer of human papillomavirus e7-specific ctl enhances tumor chemoresponse through the perforin/granzyme-mediated pathway. | adoptive cytotoxic t lymphocyte (ctl) therapy has an important implication in treating cancer patients. here, we investigate whether adoptive transfer of human papillomavirus (hpv) e7-specific ctl can enhance tumor chemoresponse using an established cervical cancer animal model. cisplatin-based chemotherapy plus ctl therapy showed an improved therapeutic effectiveness, along with antitumor protective responses to a parental tumor cell rechallenge. cisplatin treatment dose-dependently increased t ... | 2009 | 19277009 |
| dual mechanism for the translation of subgenomic mrna from sindbis virus in infected and uninfected cells. | infection of bhk cells by sindbis virus (sv) gives rise to a profound inhibition of cellular protein synthesis, whereas translation of viral subgenomic mrna that encodes viral structural proteins, continues for hours. to gain further knowledge on the mechanism by which this subgenomic mrna is translated, the requirements for some initiation factors (eifs) and for the presence of the initiator aug were examined both in infected and in uninfected cells. to this end, bhk cells were transfected with ... | 2009 | 19274090 |
| post-epidemic chikungunya disease on reunion island: course of rheumatic manifestations and associated factors over a 15-month period. | although the acute manifestations of chikungunya virus (chikv) illness are well-documented, few data exist about the long-term rheumatic outcomes of chikv-infected patients. we undertook between june and september 2006 a retrospective cohort study aimed at assessing the course of late rheumatic manifestations and investigating potential risk factors associated with the persistence of these rheumatic manifestations over 15 months. 147 participants (>16 yrs) with laboratory-confirmed chikv disease ... | 2009 | 19274071 |
| distinct regulation of autophagic activity by atg14l and rubicon associated with beclin 1-phosphatidylinositol-3-kinase complex. | beclin 1, a mammalian autophagy protein that has been implicated in development, tumour suppression, neurodegeneration and cell death, exists in a complex with vps34, the class iii phosphatidylinositol-3-kinase (pi(3)k) that mediates multiple vesicle-trafficking processes including endocytosis and autophagy. however, the precise role of the beclin 1-vps34 complex in autophagy regulation remains to be elucidated. combining mouse genetics and biochemistry, we have identified a large in vivo beclin ... | 2009 | 19270693 |
| dynamin-dependent membrane drift recruits ampa receptors to dendritic spines. | the surface expression and localization of ampa receptors (ampars) at dendritic spines are tightly controlled to regulate synaptic transmission. here we show that de novo exocytosis of the glur2 ampar subunit occurs at the dendritic shaft and that new ampars diffuse into spines by lateral diffusion in the membrane. however, membrane topology restricts this lateral diffusion. we therefore investigated which mechanisms recruit ampars to spines from the shaft and demonstrated that inhibition of dyn ... | 2009 | 19269965 |
| suppression of rna interference increases alphavirus replication and virus-associated mortality in aedes aegypti mosquitoes. | arthropod-borne viruses (arboviruses) can persistently infect and cause limited damage to mosquito vectors. rna interference (rnai) is a mosquito antiviral response important in restricting rna virus replication and has been shown to be active against some arboviruses. the goal of this study was to use a recombinant sindbis virus (sinv; family togaviridae; genus alphavirus) that expresses b2 protein of flock house virus (fhv; family nodaviridae; genus alphanodavirus), a protein that inhibits rna ... | 2009 | 19265532 |
| autophagy and its role in mhc-mediated antigen presentation. | intracellular degradation by autophagy plays a role in the maintenance of cellular homeostasis under normal conditions and during periods of cellular stress. autophagy has also been implicated in several other cellular processes including immune recognition and responsiveness. more specifically, autophagy has been identified as a route by which cytoplasmic and nuclear ag are delivered to mhc class ii molecules for presentation to cd4(+) t cells. autophagy has also recently been implicated in mhc ... | 0 | 19265109 |
| suppression of host gene expression by nsp1 proteins of group 2 bat coronaviruses. | nsp1 protein of severe acute respiratory syndrome coronavirus (sars-cov), a group 2b cov, suppresses host gene expression by promoting host mrna degradation and translation inhibition. the present study analyzed the activities of nsp1 proteins from the group 2 bat cov strains rm1, 133, and hku9-1, belonging to groups 2b, 2c, and 2d, respectively. the host mrna degradation and translational suppression activities of nsp1 of sars-cov and rm1 nsp1 were similar and stronger than the activities of th ... | 2009 | 19264783 |
| pkr acts early in infection to suppress semliki forest virus production and strongly enhances the type i interferon response. | the double-stranded rna-activated protein kinase (pkr) is a key regulator of protein translation, interferon (ifn) expression and cell survival. upon infection of vertebrate cells in continuous culture, the alphavirus semliki forest virus (sfv) initiates apoptosis and ifn synthesis. to determine the effect of pkr on sfv infection, we studied the course of infection in wild-type (wt) mice, mice with a genetic deletion of pkr (pkr-/-) and mouse embryo fibroblasts (mefs) derived from these mice. in ... | 2009 | 19264662 |
| autophagy, antiviral immunity, and viral countermeasures. | the autophagy pathway likely evolved not only to maintain cellular and tissue homeostasis but also to protect cells against microbial attack. this conserved mechanism by which cytoplasmic cargo is delivered to the endolysosomal system is now recognized as a central player in coordinating the host response to diverse intracellular pathogens, including viruses. as an endolysosomal delivery system, autophagy functions in the transfer of viruses from the cytoplasm to the lysosome where they are degr ... | 2009 | 19264100 |
| cell type-specific targeting with surface-engineered lentiviral vectors co-displaying okt3 antibody and fusogenic molecule. | the purpose of this study was to investigate the potential of a t-cell-related targeting method using a lentiviral vector-based gene delivery system. | 2009 | 19259792 |
| anti-apoptotic effects of protein kinase c-delta and c-fos in cisplatin-treated thyroid cells. | we showed previously that cisplatin inititates a signalling pathway mediated by pkc-delta/extracellular signal-regulated kinase (erk), important for maintaining viability in pc cl3 thyroid cells. the studies described herein examined whether c-fos was associated with cisplatin resistance and the signalling link between c-fos and pkc-delta/erk. | 2009 | 19254279 |
| development of hepatitis c virus vaccines: challenges and progress. | development of an effective vaccine against the hepatitis c virus (hcv) has long been defined as a difficult challenge due to the considerable variability of this rna virus and the observation that convalescent humans and chimpanzees could be re-infected after re-exposure. on the other hand, progress in the understanding of antiviral immune responses in patients with viral clearance has elucidated key mechanisms playing a role in the control of viral infection. studies investigating prophylactic ... | 2009 | 19249975 |
| identification of thieno[3,2-b]pyrrole derivatives as novel small molecule inhibitors of neurotropic alphaviruses. | neurotropic alphaviruses such as western, eastern, and venezuelan equine encephalitis viruses cause serious and potentially fatal central nervous system infections in humans and are high-priority potential bioterrorism agents. there are currently no widely available vaccines or licensed therapies for these virulent pathogens. to identify potential novel antiviral drugs, we developed a cell-based assay with a western equine encephalitis virus replicon that expresses a luciferase reporter gene and ... | 2009 | 19239364 |
| identification and analysis of putative promoter motifs in flavivirus genome. | the genus flavivirus comprises medically significant pathogenic virus; causing several infections in humans worldwide. flavivirus genomes are 10-11 kb approximately and encode both structural and non structural region. the non structural region plays fundamental role in the stability, regulation and cell cycle of virus. the complete genomes of 26 flavivirus were used for identification of promoter motifs through in silico approaches. the promoter sequences were encoded in merely 16 viruses and 1 ... | 2008 | 19238240 |
| role of bnip3 and nix in cell death, autophagy, and mitophagy. | bnip3 and nix are proteins related to the bh3-only family, which induce both cell death and autophagy. consistent with their ability to induce cell death, bnip3 and nix are implicated in the pathogenesis of cancer and heart disease. in tumor cells, bnip3 and nix are regulated by hypoxia, and the deregulation of bnip3 or nix expression is associated with tumor growth. in heart muscle, bnip3 and nix are regulated by hypoxia and galphaq-dependent signaling, respectively, and their expression is ass ... | 2009 | 19229244 |
| the regulation of disassembly of alphavirus cores. | alphaviruses are used as model viruses for structure determination and for analysis of virus entry. they are used also as vectors for protein expression and gene therapy. virus particles are assembled by budding, using preformed cores and a modified cellular membrane. during entry, alphaviruses release the viral core into the cytoplasm. cores are disassembled during virus entry and accumulate in the cytoplasm during virus multiplication. the regulation of core disassembly is the subject of this ... | 2009 | 19225713 |
| low-density macroarray for rapid detection and identification of crimean-congo hemorrhagic fever virus. | crimean-congo hemorrhagic fever (cchf) is a tick-borne viral zoonosis which occurs throughout africa, eastern europe, and asia and results in an approximately 30% fatality rate. a reverse transcription-pcr assay including a competitive internal control was developed on the basis of the most up-to-date genome information. biotinylated amplification products were hybridized to dna macroarrays on the surfaces of polymer supports, and hybridization events were visualized by incubation with a strepta ... | 2009 | 19225100 |
| antiviral immunity in drosophila. | genetic analysis of the drosophila antiviral response indicates that rna interference plays a major role. this contrasts with the situation in mammals, where interferon-induced responses mediate innate antiviral host-defense. an inducible response also contributes to antiviral immunity in drosophila, and similarities in the sensing and signaling of viral infection are becoming apparent between drosophila and mammals. in particular, dexd/h box helicases appear to play a crucial role in the cytoso ... | 2009 | 19223163 |
| characterization of a mimivirus rna cap guanine-n2 methyltransferase. | a 2,2,7-trimethylguanosine (tmg) cap is a signature feature of eukaryal snrnas, telomerase rnas, and trans-spliced nematode mrnas. tmg and 2,7-dimethylguanosine (dmg) caps are also present on mrnas of two species of alphaviruses (positive strand rna viruses of the togaviridae family). it is presently not known how viral mrnas might acquire a hypermethylated cap. mimivirus, a giant dna virus that infects amoeba, encodes many putative enzymes and proteins implicated in rna transactions, including ... | 2009 | 19218551 |
| caspase inhibitor p35 is required for the production of robust baculovirus virions in trichoplusia ni tn-368 cells. | apoptosis can protect lepidopteran insects against baculovirus infection by limiting viral replication. baculoviruses counter this response by expressing anti-apoptotic proteins such as the caspase inhibitor p35, which is expressed by several baculoviruses including autographa californica mutiple nucleopolyhedrovirus (acmnpv). mutants of acmnpv that lack the p35 gene induce apoptosis in spodoptera frugiperda cells, and replication of these mutants is severely curtailed in s. frugiperda cell line ... | 2009 | 19218211 |
| dengue virus type 2 infections of aedes aegypti are modulated by the mosquito's rna interference pathway. | a number of studies have shown that both innate and adaptive immune defense mechanisms greatly influence the course of human dengue virus (denv) infections, but little is known about the innate immune response of the mosquito vector aedes aegypti to arbovirus infection. we present evidence here that a major component of the mosquito innate immune response, rna interference (rnai), is an important modulator of mosquito infections. the rnai response is triggered by double-stranded rna (dsrna), whi ... | 2009 | 19214215 |
| apoptosis in murine norovirus-infected raw264.7 cells is associated with downregulation of survivin. | noroviruses (nvs) are recognized as a major cause of nonbacterial gastroenteritis in humans. studies of the human nvs continue to be hampered by the inability to propagate them in any cell culture system. until recently, most data concerning nv replication were derived from studies of feline calicivirus and rabbit hemorrhagic disease virus, which are cultivable members of the family caliciviridae. from such studies, it was proposed that caliciviruses induce apoptosis to facilitate the disseminat ... | 2009 | 19211757 |
| gamma-herpesvirus-induced protection against bacterial infection is transient. | herpesviruses are widely disseminated in the population and establish lifelong latency, which is associated with a variety of pathological consequences. a recent report showed that mice latently infected with either murine gamma-herpesvirus-68 (gammahv68) or murine cytomegalovirus (mcmv), mouse pathogens genetically similar to the human herpesviruses, epstein-barr virus, kaposi's sarcoma-associated herpesvirus, and cytomegalovirus, had enhanced resistance to subsequent bacterial infection, sugge ... | 2009 | 19210230 |
| antiviral immunity in drosophila requires systemic rna interference spread. | multicellular organisms evolved sophisticated defence systems to confer protection against pathogens. an important characteristic of these immune systems is their ability to act both locally at the site of infection and at distal uninfected locations. in insects, such as drosophila melanogaster, rna interference (rnai) mediates antiviral immunity. however, the antiviral rnai defence in flies seems to be a local, cell-autonomous process, as flies are thought to be unable to generate a systemic rn ... | 2009 | 19204732 |
| sindbis vectors: illuminating the path to ovarian cancer therapy. | 2005 | 19202635 | |
| an improved in vitro and in vivo sindbis virus expression system through host and virus engineering. | the sindbis viral expression system enables the rapid production of high levels of recombinant protein in mammalian cells; however, this expression is typically limited to transient production due to the cytotoxicity of the virus. limiting the lethality inherent in the sindbis virus vector in order to enable long term, sustained expression of recombinant proteins may be possible. in this study, modifications to virus and host have been combined in order to reduce the cytopathic effects. non-cyto ... | 2009 | 19200810 |
| lrp/lr as an alternative promising target in therapy of prion diseases, alzheimer's disease and cancer. | the 37 kda/67 kda laminin receptor (lrp/lr) represents a key player for cell adhesion, is associated with the metastatic potential of solid tumors and is required for maintenance of cell viability by preventing apoptosis. lrp/lr acts as a receptor for viruses such as sindbis virus, venezuelean equine encephalitis (vee) virus, adeno-associated-viruses (aav) and dengue virus, the latter causing 50 to 100 million infections in humans per year. lrp/lr acts further as a receptor for prions and repres ... | 2009 | 19200017 |
| creation of interferon-alpha8 mutants with amino acid substitutions against interferon-alpha receptor-2 binding sites using phage display system and evaluation of their biologic properties. | in this study, we describe the creation of three interferon-alpha (ifn-alpha)8 mutants with markedly higher antiviral and antiproliferative activities in comparison with those of the wild-type (wt)ifn-alpha8, wtifn-alpha2, and ifn-con1 using a phage display system. sequence analysis showed that three out of the six hot-spot amino acid residues of wtifn-alpha8 known to be important for the interaction with the ifn-alpha receptor-2 (ifnar-2)-binding sites were substituted to other amino acids and ... | 2009 | 19196068 |
| learning from the viral journey: how to enter cells and how to overcome intracellular barriers to reach the nucleus. | viruses deliver their genome into host cells where they subsequently replicate and multiply. a variety of relevant strategies have evolved by which viruses gain intracellular access and utilize cellular machinery for the synthesis of their genome. therefore, the viral journey provides insight into the cell's trafficking machinery and how it can be best exploited to improve nonviral gene delivery systems. this review summarizes viral internalization pathways and intracellular trafficking of virus ... | 2009 | 19194803 |
| noncytolytic clearance of sindbis virus infection from neurons by gamma interferon is dependent on jak/stat signaling. | the alphavirus sindbis virus (sinv) causes encephalomyelitis in mice by infecting neurons of the brain and spinal cord. the outcome is age dependent. young animals develop fatal disease, while older animals recover from infection. recovery requires noncytolytic clearance of sinv from neurons, and gamma interferon (ifn-gamma) is an important contributor to clearance in vivo. ifn-gamma-dependent clearance has been studied using immortalized csm14.1 rat neuronal cells that can be differentiated in ... | 2009 | 19176616 |
| two types of thalamocortical projections from the motor thalamic nuclei of the rat: a single neuron-tracing study using viral vectors. | the axonal arborization of single motor thalamic neurons was examined in rat brain using a viral vector expressing membrane-targeted palmitoylation site-attached green fluorescent protein (palgfp). we first divided the ventral anterior-ventral lateral motor thalamic nuclei into 1) the rostromedial portion, which was designated inhibitory afferent-dominant zone (iz) with intense glutamate decarboxylase immunoreactivity and weak vesicular glutamate transporter 2 immunoreactivity, and 2) the caudol ... | 2009 | 19174446 |
| in vitro activity and preclinical profile of tmc435350, a potent hepatitis c virus protease inhibitor. | the hepatitis c virus (hcv) ns3/4a serine protease has been explored as a target for the inhibition of viral replication in preclinical models and in hcv-infected patients. tmc435350 is a highly specific and potent inhibitor of ns3/4a protease selected from a series of novel macrocyclic inhibitors. in biochemical assays using ns3/4a proteases of genotypes 1a and 1b, inhibition constants of 0.5 and 0.4 nm, respectively, were determined. tmc435350 inhibited hcv replication in a cellular assay (sub ... | 2009 | 19171797 |
| an alphavirus replicon-derived candidate vaccine against rift valley fever virus. | rift valley fever virus (rvfv) is a mosquito-transmitted bunyavirus (genus phlebovirus) associated with severe disease in livestock and fatal encephalitis or haemorrhagic fever in a proportion of infected humans. although live attenuated and inactivated vaccines have been used in livestock, and on a limited scale in humans, there is a need for improved anti-rvfv vaccines. towards this goal, sindbis virus replicon vectors expressing the rvfv gn and gc glycoproteins, as well as the non-structural ... | 2009 | 19171081 |
| gene expression studies in mosquitoes. | research on gene expression in mosquitoes is motivated by both basic and applied interests. studies of genes involved in hematophagy, reproduction, olfaction, and immune responses reveal an exquisite confluence of biological adaptations that result in these highly-successful life forms. the requirement of female mosquitoes for a bloodmeal for propagation has been exploited by a wide diversity of viral, protozoan and metazoan pathogens as part of their life cycles. identifying genes involved in h ... | 2008 | 19161831 |
| targeted transduction of cd34+ hematopoietic progenitor cells in nonpurified human mobilized peripheral blood mononuclear cells. | conventional gene-therapy applications of hematopoietic stem cells (hscs) involve purification of cd34+ progenitor cells from the mobilized peripheral blood, ex vivo transduction of the gene of interest into them, and reinfusion of the transduced cd34+ progenitor cells into patients. eliminating the process of purification would save labor, time and money, while enhancing hscs viability, transplantability and pluripotency. lentiviral vectors have been widely used in gene therapy because they inf ... | 2009 | 19152374 |
| apoptosis in animal models of virus-induced disease. | apoptosis is associated with virus-induced human diseases of the central nervous system, heart and liver, and causes substantial morbidity and mortality. although virus-induced apoptosis is well characterized in individual cells in cell culture, virus-induced apoptosis in vivo and the role of apoptosis in virus-induced disease is not well established. this review focuses on animal models of virus-induced diseases of the central nervous system, heart and liver that provide insights into the role ... | 2009 | 19148180 |
| coordinated changes in dendritic arborization and synaptic strength during neural circuit development. | neural circuit development requires concurrent morphological and functional changes. here, we identify coordinated and inversely correlated changes in dendritic morphology and mepsc amplitude following increased neural activity. we show that overexpression of beta-catenin, a molecule that increases total dendritic length, mimics the effects of increased neuronal activity by scaling down mepsc amplitudes, while postsynaptic expression of a protein that sequesters beta-catenin reverses the effects ... | 2009 | 19146814 |
| analysis of the survival of venezuelan equine encephalomyelitis virus and possible viral simulants in liquid suspensions. | to compare the inactivation rate of venezuelan equine encephalomyelitis (vee) virus in liquids to that of sindbis virus (sv, another alphavirus) and to a bacteriophage (ms2) generally used as a viral simulant in the development of countermeasures in biodefense. | 2008 | 19146486 |
| helical virus particles formed from morphological subunits of a membrane containing icosahedral virus. | the classic publication by caspar and klug in 1962 [physical principles in the construction of regular viruses. cold spring harbor symp. quant. biol. 27:1-24.] has formed the basis of much research on virus assembly. caspar and klug predicted that a single virus morphological unit could form a two dimensional lattice composed of 6-fold arrays (primitive plane), a family of icosahedra of increasing triangulation numbers (t) and helical arrays of varying length. we have shown that icosahedral viru ... | 2009 | 19144371 |
| a haemocyte tropism for an arbovirus. | horizontally transmitted mosquito-borne viruses enter the midgut with a blood meal then disseminate to infect the salivary glands. en route to the salivary glands, these viruses encounter the plasma (haemolymph) and blood cells (haemocytes). haemocytes respond to a variety of micro-organisms, but their role in virus replication and dissemination has not been described. to look for a potential haemocyte tropism for an arbovirus, a sindbis virus was injected intrathoracically into four species of ... | 2009 | 19141437 |
| biochemical and biophysical comparison of cleaved and uncleaved soluble, trimeric hiv-1 envelope glycoproteins. | human immunodeficiency virus type 1 (hiv-1) entry into host cells is mediated by the trimeric envelope glycoprotein complex (env). accordingly, the env proteins are the targets for neutralizing antibodies (nabs) and are the focus of vaccines intended to induce nabs. because the env complex is labile, soluble recombinant env (gp140) trimers require engineering to stabilize them sufficiently for use as immunogens. trimeric forms of gp140 trimers can be created that are either cleavage-competent or ... | 2009 | 19135223 |
| beclin-1 expression is a predictor of clinical outcome in patients with esophageal squamous cell carcinoma and correlated to hypoxia-inducible factor (hif)-1alpha expression. | in the present study, we examined the relationship between beclin-1 expression and hif-1alpha expression in esophageal squamous cell carcinoma(escc). there was a loss of beclin-1 protein expression in 33% of esccs. beclin-1 expression significantly correlated with depth of invasion, lymph node metastasis and clinical stage. among the 54 patients, the survival rate of the beclin-1-positive group was better than that of the beclin-1-negative group. twenty-five of the 54 (46%) tumor specimens showe ... | 2009 | 19130303 |
| sindbis virus-based measles dna vaccines protect cotton rats against respiratory measles: relevance of antibodies, mucosal and systemic antibody-secreting cells, memory b cells, and th1-type cytokines as correlates of immunity. | measles remains an important cause of pediatric morbidity and mortality in developing countries, especially among infants who are too young to receive the current licensed live attenuated measles vaccine. we developed two sindbis virus dna vaccines encoding the measles virus hemagglutinin (pmsin-h) and fusion proteins (pmsinh-fdu) and examined their immunogenicities and protective efficacies when administered alone or followed by the live measles virus vaccine in cotton rats. neutralizing antibo ... | 2009 | 19129445 |
| mucosally delivered salmonella typhi expressing the yersinia pestis f1 antigen elicits mucosal and systemic immunity early in life and primes the neonatal immune system for a vigorous anamnestic response to parenteral f1 boost. | neonates respond poorly to conventional vaccines. this has been attributed, in part, to the immaturity of neonatal dendritic cells that lack full capacity for ag presentation and t cell stimulation. we engineered an attenuated salmonella typhi strain to express and export the f1 ag of y. pestis (s. typhi(f1)) and investigated its immunogenicity early in life using a heterologous prime-boost regimen. newborn mice primed intranasally with a single dose of s. typhi(f1) elicited mucosal ab- and ifn- ... | 2009 | 19124765 |
| rna-based viral immunity initiated by the dicer family of host immune receptors. | suppression of viral infection by rna in a nucleotide sequence homology-dependent manner was first reported in plants in early 1990 s. studies in the past 15 years have established a completely new rna-based immune system against viruses that is mechanistically related to rna silencing or rna interference (rnai). this viral immunity begins with recognition of viral double-stranded or structured rna by the dicer nuclease family of host immune receptors. in fungi, plants and invertebrates, the vir ... | 2009 | 19120484 |
| substitutions of 169lys and 173thr in nonstructural protein 1 influence the infectivity and pathogenicity of xj-160 virus. | an infectious clone (pbr-xj160) was constructed using the full-length cdna of the sindbis-like xj-160 virus. two nucleotide mutations, causing amino acid changes at residue 169 from lys to arg and at residue 173 from thr to ile in the nonstructural protein (nsp) 1 coding region, strongly influenced the infectivity of in vitro-synthesized rna. we used site-directed mutagenesis to obtain clones encoding a change to arg at residue 169 of nsp1 (pbr-169), a change to ile at residue 173 (pbr-173), or ... | 2009 | 19118404 |
| independent regulation of reovirus membrane penetration and apoptosis by the mu1 phi domain. | apoptosis plays an important role in the pathogenesis of reovirus encephalitis. reovirus outer-capsid protein mu1, which functions to penetrate host cell membranes during viral entry, is the primary regulator of apoptosis following reovirus infection. ectopic expression of full-length and truncated forms of mu1 indicates that the mu1 phi domain is sufficient to elicit a cell death response. to evaluate the contribution of the mu1 phi domain to the induction of apoptosis following reovirus infect ... | 2008 | 19112493 |
| transgenesis approaches for functional analysis of peptidergic cells in the silkworm bombyx mori. | the domestic silkworm, bombyx mori represents an insect model of great scientific and economic importance. besides the establishment of a stable germline transformation using the piggybac vector, technically feasible methods for in vivo gene delivery and transient gene expression were developed using viral based vectors, especially sindbis viruses and baculoviruses. the recombinant baculovirus, autographa californica multiple nucleopolyhedrovirus (acmnpv), commonly used for large-scale protein p ... | 2009 | 19111552 |
| host responses to wild-type and attenuated herpes simplex virus infection in the absence of stat1. | humans and mice lacking the interferon signaling molecule stat1 are sensitive to a variety of pathogens due to their presumed inability to mount a strong innate immune response. the herpes simplex virus type 1 (hsv-1) virion host shutoff (vhs) protein is a multifunctional immunomodulator that counteracts the innate immune response and viruses lacking vhs are attenuated and effective live vaccines in animal models. to investigate the interplay of viruses with an immunocompromised host, we perform ... | 2009 | 19109391 |
| role of conserved cysteines in the alphavirus e3 protein. | alphavirus particles are covered by 80 glycoprotein spikes that are essential for viral entry. spikes consist of the e2 receptor binding protein and the e1 fusion protein. spike assembly occurs in the endoplasmic reticulum, where e1 associates with pe2, a precursor containing e3 and e2 proteins. e3 is a small, cysteine-rich, extracellular glycoprotein that mediates proper folding of pe2 and its subsequent association with e1. in addition, cleavage of e3 from the assembled spike is required to ma ... | 2009 | 19109378 |
| larval competition differentially affects arbovirus infection in aedes mosquitoes. | both density-mediated and trait-mediated indirect biotic interactions may be important in structuring communities. indirect interactions in many study systems remain unexplored; in part, because they are often difficult to detect, and in many instances, have been identified empirically only when unexpected results arise. indirect effects induced by competition may be particularly important among organisms with complex life cycles, wherein competitive effects experienced in one life stage influen ... | 2005 | 19096729 |
| induction of immune responses and protection in mice against rabies using a self-replicating rna vaccine encoding rabies virus glycoprotein. | a self-replicating rna vaccine encoding rabies virus glycoprotein gene was developed utilizing sindbis virus rna replicon. the in vitro transcribed rna (sin-rab-g rna) was transfected in mammalian cells and analysed for self-replication and expression of rabies glycoprotein. to generate immune responses against rabies, mice were immunized with 10microg of sin-rab-g rna and immune responses developed were compared with mice immunized with rabies dna vaccine and commercial cell culture vaccine (ra ... | 2009 | 19081687 |
| parkin protects dopaminergic neurons against microtubule-depolymerizing toxins by attenuating microtubule-associated protein kinase activation. | mitogen-activated protein kinases, originally known as microtubule-associated protein (map) kinases, are activated in response to a variety of stimuli. here we report that microtubule-depolymerizing agents such as colchicine or nocodazole induced strong activation of map kinases including jnk, erk, and p38. this effect was markedly attenuated by parkin, whose mutations are linked to parkinson disease (pd). our previous study has shown that parkin stabilizes microtubules through strong interactio ... | 2008 | 19074146 |
| isg15 arg151 and the isg15-conjugating enzyme ube1l are important for innate immune control of sindbis virus. | interferon (ifn)-stimulated gene 15 (isg15) is a ubiquitin-like molecule that conjugates to target proteins via a c-terminal lrlrgg motif and has antiviral function in vivo. we used structural modeling to predict human isg15 (hisg15) residues important for interacting with its e1 enzyme, ube1l. kinetic analysis revealed that mutation of arginine 153 to alanine (r153a) ablated hisg15-hube1l binding and transthiolation of ubch8. mutation of other predicted ube1l-interacting residues had minimal ef ... | 2009 | 19073728 |
| photoinactivation of sindbis virus infectivity without inhibition of membrane fusion. | photoinactivation of enveloped viruses is commonly associated with damage to fusion proteins and inhibition of membrane fusion capacity. here we show that photobleaching of sindbis virus labeled with the membrane localized dye, r18 (octadecyl rhodamine b) causes a dramatic loss of infectivity without observable changes in low-ph triggered membrane fusion to liposomes. sindbis labeled with dii (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) also maintains low-ph triggered mem ... | 2009 | 19067945 |
| ifn-gamma-mediated suppression of coronavirus replication in glial-committed progenitor cells. | the neurotropic jhm strain of mouse hepatitis virus (jhmv) replicates primarily within glial cells following intracranial inoculation of susceptible mice, with relative sparing of neurons. this study demonstrates that glial cells derived from neural progenitor cells are susceptible to jhmv infection and that treatment of infected cells with ifn-gamma inhibits viral replication in a dose-dependent manner. although type i ifn production is muted in jhmv-infected glial cultures, ifn-beta is produce ... | 2009 | 19059617 |
| role of tlr3 in the immunogenicity of replicon plasmid-based vaccines. | replicon plasmids encoding an alphavirus rna replicase constitute an alternative to conventional dna plasmids with promise for dna vaccination in humans. replicase activity amplifies the levels of transgene mrna through a copying process involving double-stranded (ds) rna intermediates, which contribute to vaccine immunogenicity by activating innate antiviral responses. toll-like receptor 3 (tlr3) is a dsrna innate immune receptor expressed by antigen-presenting dendritic cells (dcs). here, we t ... | 2009 | 19052633 |
| west nile virus-specific cd4 t cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protection. | cd4 t cells have been shown to be necessary for the prevention of encephalitis during west nile virus (wnv) infection. however, the mechanisms used by ag-specific cd4 t cells to protect mice from wnv encephalitis remain incompletely understood. contrary to the belief that cd4 t cells are protective because they merely maintain the cd8 t cell response and improve ab production, in this study we provide evidence for the direct antiviral activity of cd4 t cells that functions to protect the host fr ... | 2008 | 19050276 |
| alphavirus-derived small rnas modulate pathogenesis in disease vector mosquitoes. | mosquito-borne viruses cause significant levels of morbidity and mortality in humans and domesticated animals. maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. although the vertebrate infection is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosq ... | 2008 | 19047642 |
| yellow fever vaccine induces integrated multilineage and polyfunctional immune responses. | correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. this impedes the development of novel vaccines to incurable diseases such as hiv and cancer. in this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (yf) vaccine 17d (yf17d) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. we show that immunization with yf17d leads to an integrated immune r ... | 2008 | 19047440 |
| rapid, bidirectional remodeling of synaptic nmda receptor subunit composition by a-type k+ channel activity in hippocampal ca1 pyramidal neurons. | the transient, a-type k+ current (ia) controls the excitability of ca1 pyramidal neuron dendrites by regulating the back-propagation of action potentials and by shaping synaptic input. dendritic a-type k+ channels are targeted for modulation during long-term potentiation (ltp) and we have recently shown that activity-dependent internalization of the a-type channel subunit kv4.2 enhances synaptic currents. however, the effect of changes in ia on the ability to induce subsequent synaptic plasticit ... | 2008 | 19038222 |
| rotavirus architecture at subnanometer resolution. | rotavirus, a nonturreted member of the reoviridae, is the causative agent of severe infantile diarrhea. the double-stranded rna genome encodes six structural proteins that make up the triple-layer particle. x-ray crystallography has elucidated the structure of one of these capsid proteins, vp6, and two domains from vp4, the spike protein. complementing this work, electron cryomicroscopy (cryoem) has provided relatively low-resolution structures for the triple-layer capsid in several biochemical ... | 2009 | 19036817 |
| characterization of purified sindbis virus nsp4 rna-dependent rna polymerase activity in vitro. | the sindbis virus rna-dependent rna polymerase (nsp4) is responsible for the replication of the viral rna genome. in infected cells, nsp4 is localized in a replication complex along with the other viral non-structural proteins. nsp4 has been difficult to homogenously purify from infected cells due to its interactions with the other replication proteins and the fact that its n-terminal residue, a tyrosine, causes the protein to be rapidly turned over in cells. we report the successful expression ... | 2009 | 19036396 |
| investigating the mechanisms underlying neuronal death in ischemia using in vitro oxygen-glucose deprivation: potential involvement of protein sumoylation. | it is well established that brain ischemia can cause neuronal death via different signaling cascades. the relative importance and interrelationships between these pathways, however, remain poorly understood. here is presented an overview of studies using oxygen-glucose deprivation of organotypic hippocampal slice cultures to investigate the molecular mechanisms involved in ischemia. the culturing techniques, setup of the oxygen-glucose deprivation model, and analytical tools are reviewed. the au ... | 0 | 19029060 |
| a critical role of a cellular membrane traffic protein in poliovirus rna replication. | replication of many rna viruses is accompanied by extensive remodeling of intracellular membranes. in poliovirus-infected cells, er and golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral rna synthesis. virus replication is inhibited by brefeldin a (bfa), implicating some components(s) of the cellular secretory pathway in virus growth. formation of characteristic vesicles induced by expression of viral proteins was not inhibited by bfa, but they were functi ... | 2008 | 19023417 |
| probing protein structure by amino acid-specific covalent labeling and mass spectrometry. | for many years, amino acid-specific covalent labeling has been a valuable tool to study protein structure and protein interactions, especially for systems that are difficult to study by other means. these covalent labeling methods typically map protein structure and interactions by measuring the differential reactivity of amino acid side chains. the reactivity of amino acids in proteins generally depends on the accessibility of the side chain to the reagent, the inherent reactivity of the label ... | 2009 | 19016300 |
| mvps34 is activated following high-resistance contractions. | following resistance exercise in the fasted state, both protein synthesis and degradation in skeletal muscle are increased. the addition of essential amino acids potentiates the synthetic response suggesting that an amino acid sensor, which is involved in both synthesis and degradation, may be activated by resistance exercise. one such candidate protein is the class 3 phosphatidylinositol 3oh-kinase (pi3k) vps34. to determine whether mammalian vps34 (mvps34) is modulated by high-resistance contr ... | 2009 | 19015198 |
| molecular cloning, overproduction, purification and biochemical characterization of the p39 nsp2 protease domains encoded by three alphaviruses. | alphaviruses cause serious diseases that pose a potential health threat to both humans and livestock. the nonstructural protein 2 (nsp2) encoded by alphaviruses is a multifunctional enzyme that is essential for viral replication and maturation. its 39-kda c-terminal domain (nsp2pro) is a cysteine protease that is responsible for cleaving a viral polyprotein at three sites to generate nonstructural proteins 1, 2, 3 and 4. in the present study, we evaluated nsp2pro domains from the following three ... | 2009 | 19013248 |
| light-induced rescue of breathing after spinal cord injury. | paralysis is a major consequence of spinal cord injury (sci). after cervical sci, respiratory deficits can result through interruption of descending presynaptic inputs to respiratory motor neurons in the spinal cord. expression of channelrhodopsin-2 (chr2) and photostimulation in neurons affects neuronal excitability and produces action potentials without any kind of presynaptic inputs. we hypothesized that after transducing spinal neurons in and around the phrenic motor pool to express chr2, ph ... | 2008 | 19005051 |
| human immunodeficiency virus type 1 env trimer immunization of macaques and impact of priming with viral vector or stabilized core protein. | currently there is limited information about the quality of immune responses elicited by candidate human immunodeficiency virus type 1 (hiv-1) envelope glycoprotein (env)-based immunogens in primates. here we describe a comprehensive analysis of neutralizing antibody and t-cell responses obtained in cynomolgus macaques by three selected immunization regimens. we used the previously described yu2-based gp140 protein trimers administered in an adjuvant, preceded by two distinct priming strategies: ... | 2009 | 19004960 |
| mice lacking the isg15 e1 enzyme ube1l demonstrate increased susceptibility to both mouse-adapted and non-mouse-adapted influenza b virus infection. | isg15 functions as a critical antiviral molecule against influenza virus, with infection inducing both the conjugation of isg15 to target proteins and production of free isg15. here, we report that mice lacking the isg15 e1 enzyme ube1l fail to form isg15 conjugates. both ube1l(-/-) and isg15(-/-) mice display increased susceptibility to influenza b virus infection, including non-mouse-adapted strains. finally, we demonstrate that isg15 controls influenza b virus infection through its action wit ... | 2009 | 19004958 |
| viral-mediated expression of a constitutively active form of creb in hippocampal neurons increases memory. | synaptic activity-dependent phosphorylation of the transcription factor camp response element binding protein (creb) leads to creb-dependent gene transcription, a process thought to underlie long-term hippocampal synaptic plasticity and memory formation. we previously reported that increasing creb activity in glutamatergic neurons enhances synaptic plasticity and neuronal excitability. whether these modifications are sufficient to promote hippocampal-dependent memory formation was not determined ... | 2009 | 19004015 |
| therapeutic and prophylactic applications of alphavirus vectors. | alphavirus vectors are high-level, transient expression vectors for therapeutic and prophylactic use. these positive-stranded rna vectors, derived from semliki forest virus, sindbis virus and venezuelan equine encephalitis virus, multiply and are expressed in the cytoplasm of most vertebrate cells, including human cells. part of the genome encoding the structural protein genes, which is amplified during a normal infection, is replaced by a transgene. three types of vector have been developed: vi ... | 2008 | 19000329 |
| ex vivo promoter analysis of antiviral heat shock cognate 70b gene in anopheles gambiae. | the anopheles gambiae heat shock cognate gene (hsc70b) encodes a constitutively expressed protein in the hsp70 family and it functions as a molecular chaperone for protein folding. however, the expression of hsc70b can be further induced by certain stimuli such as heat shock and infection. we previously demonstrated that the an. gambiae hsc70b is induced during o'nyong-nyong virus (onnv) infection and subsequently suppresses onnv replication in the mosquito. to further characterize the inducibil ... | 2008 | 18986525 |
| size alters susceptibility of vectors to dengue virus infection and dissemination. | the size of arthropod vectors may affect their ability to transmit pathogens. here we test the hypothesis that body size alters the susceptibility of aedes aegypti and aedes albopictus mosquitoes to dengue virus (denv) infection and subsequent dissemination throughout the body of the mosquito. after feeding on blood containing known quantities of virus, smaller-sized females were significantly more likely to become infected and to disseminate virus than larger individuals. the effects of size we ... | 2008 | 18981505 |
| genome 3'-end repair in dengue virus type 2. | genomes of rna viruses encounter a continual threat from host cellular ribonucleases. therefore, viruses have evolved mechanisms to protect the integrity of their genomes. to study the mechanism of 3'-end repair in dengue virus-2 in mammalian cells, a series of 3'-end deletions in the genome were evaluated for virus replication by detection of viral antigen ns1 and by sequence analysis. limited deletions did not cause any delay in the detection of ns1 within 5 d. however, deletions of 7-10 nucle ... | 2008 | 18974278 |
| a protein that replaces the entire cellular eif4f complex. | the eif4f cap-binding complex mediates the initiation of cellular mrna translation. eif4f is composed of eif4e, which binds to the mrna cap, eif4g, which indirectly links the mrna cap with the 43s pre-initiation complex, and eif4a, which is a helicase necessary for initiation. viral nucleocapsid proteins (n) function in both genome replication and rna encapsidation. surprisingly, we find that hantavirus n has multiple intrinsic activities that mimic and substitute for each of the three peptides ... | 2008 | 18971945 |
| bidirectional regulation of kainate receptor surface expression in hippocampal neurons. | kainate receptors (kars) are crucial for the regulation of both excitatory and inhibitory neurotransmission, but little is known regarding the mechanisms controlling kar surface expression. we used super ecliptic phluorin (sep)-tagged kar subunit glur6a to investigate real-time changes in kar surface expression in hippocampal neurons. sindbis virus-expressed sep-glur6 subunits efficiently co-assembled with native kar subunits to form heteromeric receptors. diffuse surface-expressed dendritic sep ... | 2008 | 18955488 |
| immune response during acute chandipura viral infection in experimentally infected susceptible mice. | age dependent susceptibility was observed in chandipura virus (chpv) infected mice through intravenous and intraperitoneal route. adult mice were susceptible only through intracerebral route of infection. immature neuron and some other biological variables including immature immune system are considered to be important factor for age related susceptibility in some diseases. as chandipura virus infects both young and adult mice brain through intracerebral route the role of immune system during pe ... | 2008 | 18937835 |
| effects of inducing or inhibiting apoptosis on sindbis virus replication in mosquito cells. | sindbis virus (sinv) is a mosquito-borne virus in the genus alphavirus, family togaviridae. like most alphaviruses, sinvs exhibit lytic infection (apoptosis) in many mammalian cell types, but are generally thought to cause persistent infection with only moderate cytopathic effects in mosquito cells. however, there have been several reports of apoptotic-like cell death in mosquitoes infected with alphaviruses or flaviviruses. given that apoptosis has been shown to be an antiviral response in othe ... | 2008 | 18931060 |
| combination of active specific immunotherapy or adoptive antibody or lymphocyte immunotherapy with chemotherapy in the treatment of cancer. | successful treatment of cancer patients with a combination of monoclonal antibodies (mab) and chemotherapeutic drugs has spawned various other forms of additional combination therapies, including vaccines or adoptive lymphocyte transfer combined with chemotherapeutics. these therapies were effective against established tumors in animal models and showed promising results in initial clinical trials in cancer patients, awaiting testing in larger randomized controlled studies. although combination ... | 2008 | 18925393 |
| ross river virus envelope glycans contribute to type i interferon production in myeloid dendritic cells. | alphaviruses are mosquito-transmitted viruses that cause significant human disease, and understanding how these pathogens successfully transition from the mosquito vector to the vertebrate host is an important area of research. previous studies demonstrated that mosquito and mammalian-cell-derived alphaviruses differentially induce type i interferons (alpha/beta interferon [ifn-alpha/beta]) in myeloid dendritic cells (mdcs), where the mosquito cell-derived virus is a poor inducer of ifn-alpha/be ... | 2008 | 18922878 |
| role of thiol/disulfide exchange in newcastle disease virus entry. | newcastle disease virus (ndv) entry into host cells is mediated by the hemagglutinin-neuraminidase (hn) and fusion (f) glycoproteins. we previously showed that production of free thiols in f protein is required for membrane fusion directed by f protein (s. jain et al., j. virol. 81:2328-2339, 2007). in the present study we evaluated the oxidation state of f protein in virions and virus-like particles and its relationship to activation of f protein by hn protein, f protein conformational intermed ... | 2009 | 18922867 |
| a sindbis virus replicon-based dna vaccine encoding the rabies virus glycoprotein elicits immune responses and complete protection in mice from lethal challenge. | a sindbis virus replicon-based dna vaccine encoding rabies virus glycoprotein (g) was developed by subcloning rabies g gene into a sindbis virus replicon-based vaccine vector (palpha). the self-amplification of rna transcripts and translation efficiency of rabies g was analyzed in palpha-rab-g-transfected mammalian cells using rt-pcr, sds-page and western blot analysis. the transfected cells also showed induction of apoptosis which is an important event in the enhancement of immune responses. fu ... | 2008 | 18848857 |
| effect of host cell lipid metabolism on alphavirus replication, virion morphogenesis, and infectivity. | the alphavirus sindbis virus (sinv) causes encephalomyelitis in mice. lipid-containing membranes, particularly cholesterol and sphingomyelin (sm), play important roles in virus entry, rna replication, glycoprotein transport, and budding. levels of sm are regulated by sphingomyelinases (smases). acid smase (asmase) deficiency results in the lipid storage disease type a niemann-pick disease (npd-a), mimicked in mice by interruption of the asmase gene. we previously demonstrated that asmase-deficie ... | 2008 | 18845681 |
| beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian atg14 and uvrag. | class iii phosphatidylinositol 3-kinase (pi3-kinase) regulates multiple membrane trafficking. in yeast, two distinct pi3-kinase complexes are known: complex i (vps34, vps15, vps30/atg6, and atg14) is involved in autophagy, and complex ii (vps34, vps15, vps30/atg6, and vps38) functions in the vacuolar protein sorting pathway. atg14 and vps38 are important in inducing both complexes to exert distinct functions. in mammals, the counterparts of vps34, vps15, and vps30/atg6 have been identified as vp ... | 2008 | 18843052 |
| functional pseudotyping of human immunodeficiency virus type 1 vectors by western equine encephalitis virus envelope glycoprotein. | we investigated the ability of western equine encephalitis virus envelope glycoproteins (weev gp) to pseudotype lentiviral vectors. the titers of weev gp-pseudotyped human immunodeficiency virus type 1 (hiv) ranged as high as 8.0 x 10(4) iu/ml on permissive cells. sera from weev-infected mice specifically neutralized these pseudotypes; cell transduction was also sensitive to changes in ph. the host range of the pseudotyped particles in vitro was somewhat limited, which is atypical for most alpha ... | 2008 | 18842711 |
| passive immunization reduces murine cytomegalovirus-induced brain pathology in newborn mice. | human cytomegalovirus (hcmv) is the most frequent cause of congenital viral infections in humans and frequently leads to long-term central nervous system (cns) abnormalities that include learning disabilities, microcephaly, and hearing loss. the pathogenesis of the cns infection has not been fully elucidated and may arise as a result of direct damage of cmv-infected neurons or indirectly secondary to inflammatory response to infection. we used a recently established model of mouse cmv (mcmv) inf ... | 2008 | 18842707 |
| mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to reach a low ph compartment and infect cells. | mouse mammary tumor virus (mmtv) is a ph-dependent virus that uses mouse transferrin receptor 1 (tfr1) for entry into cells. previous studies demonstrated that mmtv could induce ph 5-dependent fusion-from-with of mouse cells. here we show that the mmtv envelope-mediated cell-cell fusion requires both the entry receptor and low ph (ph 5). although expression of the mmtv envelope and tfr1 was sufficient to mediate low ph-dependent syncytia formation, virus infection required trafficking to a low p ... | 2008 | 18829060 |
| discovery of frameshifting in alphavirus 6k resolves a 20-year enigma. | the genus alphavirus includes several potentially lethal human viruses. additionally, species such as sindbis virus and semliki forest virus are important vectors for gene therapy, vaccination and cancer research, and important models for virion assembly and structural analyses. the genome encodes nine known proteins, including the small '6k' protein. 6k appears to be involved in envelope protein processing, membrane permeabilization, virion assembly and virus budding. in protein gels, 6k migrat ... | 2008 | 18822126 |
| controlled propagation of replication-competent sindbis viral vector using suicide gene strategy. | a major concern of using viral gene therapy is the potential for uncontrolled vector propagation and infection that might result in serious deleterious effects. to enhance the safety, several viral vectors, including vectors based on sindbis virus, were engineered to lose their capability to replicate and spread after transduction of target cells. such designs, however, could dramatically reduce the therapeutic potency of the viral vectors, resulting in the need for multiple dosages to achieve t ... | 2009 | 18818670 |
| isolation of human monoclonal antibodies by mammalian cell display. | due to their low immunogenicity in patients, humanized or fully human mabs are becoming increasingly important for the treatment of a growing number of diseases, including cancer, infections, and immune disorders. here, we describe a technology allowing for the rapid isolation of fully human mabs. in contrast to previously described methods, b cells specific for an antigen of interest are directly isolated from peripheral blood mononuclear cells (pbmc) of human donors. recombinant, antigen-speci ... | 2008 | 18812621 |
| semliki forest virus strongly reduces mosquito host defence signaling. | the alphavirus genus within the togaviridae family contains several important mosquito-borne arboviruses. other than the antiviral activity of rnai, relatively little is known about alphavirus interactions with insect cell defences. here we show that semliki forest virus (sfv) infection of aedes albopictus-derived u4.4 mosquito cells reduces cellular gene expression. activation prior to sfv infection of pathways involving stat/imd, but not toll signaling reduced subsequent virus gene expression ... | 2008 | 18811601 |