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receptor-mediated entry by equine infectious anemia virus utilizes a ph-dependent endocytic pathway.previous studies of human and nonhuman primate lentiviral entry mechanisms indicate a predominant use of ph-independent pathways, although more recent studies of human immunodeficiency virus type 1 entry appear to reveal the use of a low-ph-dependent entry pathway in certain target cells. to expand the characterization of the specificity of lentiviral entry mechanisms, we have in the current study examined the entry pathway of equine infectious anemia virus (eiav) during infection of its natural ...200516282448
the aauaaa motif of bamboo mosaic virus rna is involved in minus-strand rna synthesis and plus-strand rna polyadenylation.bamboo mosaic virus (bamv) has a single-stranded positive-sense rna genome with a 5'-cap structure and a 3' poly(a) tail. deleting the internal loop that contains the putative polyadenylation signal (aauaaa) in the 3' untranslated region (utr) of bamv genomic rna appeared to diminish coat protein accumulation to 2% (c. p. cheng and c. h. tsai, j. mol. biol. 288:555-565, 1999). to investigate the function of the aauaaa motif, mutations were introduced into an infectious bamv cdna at each residue ...200516282455
human parainfluenza virus type 4 is incapable of evading the interferon-induced antiviral effect.the v proteins of some paramyxoviruses have developed the ability to efficiently inactivate stat protein function as a countermeasure for evading interferon (ifn) responses. human parainfluenza virus type 4 (hpiv4) is one of the rubulaviruses, which are members of the family paramyxoviridae, and has a v protein with a highly conserved cysteine-rich domain that is the hallmark of paramyxovirus v proteins. in order to study the function of the hpiv4 v protein, we established hela cells expressing ...200516282476
the role of the 3' terminus of the sindbis virus genome in minus-strand initiation site selection.genome replication of plus-strand rna viruses begins with the generation of a minus-strand copy of the genome. minus-strand synthesis must initiate at or close to the 3' end of the genome and progress to processive elongation to yield the appropriate template for genomic rna synthesis. the sindbis virus genome possesses a 3' polyadenylate tail preceded by a 19 nucleotide conserved sequence element (3' cse). analyses of in vitro and in vivo synthesized minus-strand rna presented in this manuscrip ...200616297426
kinetic evaluation of photosensitivity in genetically engineered neurons expressing green algae light-gated channels.neurons become photosensitive by genetically introducing one of green algae-derived protein, channelrhodopsin-2 (chr2). here, we quantitatively investigated the rapidness of the light-gated current of chr2 expressed in pc12 cells using blue light-emitting diode (led) light. the light-gated current consists of two components, inactivating and non-inactivating. the magnitude of inactivating component was almost linearly related to the light intensity. the non-inactivating component showed a tenden ...200616298005
rare earth ions block the ion pores generated by the class ii fusion proteins of alphaviruses and allow analysis of the biological functions of these pores.recently, class ii fusion proteins have been identified on the surface of alpha- and flaviviruses. these proteins have two functions besides membrane fusion: they generate an isometric lattice on the viral surface and they form ion-permeable pores at low ph. an attempt was made to identify inhibitors for the ion pores generated by the fusion proteins of the alphaviruses semliki forest virus and sindbis virus. these pores can be detected and analysed in three situations: (i) in the target membran ...200516298976
functional and genetic analysis of coronavirus replicase-transcriptase proteins.the coronavirus replicase-transcriptase complex is an assembly of viral and cellular proteins that mediate the synthesis of genome and subgenome-sized mrnas in the virus-infected cell. here, we report a genetic and functional analysis of 19 temperature-sensitive (ts) mutants of murine hepatitis virus mhv-a59 that are unable to synthesize viral rna when the infection is initiated and maintained at the non-permissive temperature. both classical and biochemical complementation analysis leads us to ...200516341254
translation of sindbis virus 26s mrna does not require intact eukariotic initiation factor 4g.the infection of baby hamster kidney (bhk) cells by sindbis virus gives rise to a drastic inhibition of cellular translation, while under these conditions the synthesis of viral structural proteins directed by the subgenomic 26s mrna takes place efficiently. here, the requirement for intact initiation factor eif4g for the translation of this subgenomic mrna has been examined. to this end, sv replicons that contain the protease of human immunodeficiency virus type 1 (hiv-1) or the poliovirus 2a(p ...200616343528
cd8+ t cells require perforin to clear west nile virus from infected neurons.injury to neurons after west nile virus (wnv) infection is believed to occur because of viral and host immune-mediated effects. previously, we demonstrated that cd8+ t cells are required for the resolution of wnv infection in the central nervous system (cns). cd8+ t cells can control infection by producing antiviral cytokines (e.g., gamma interferon or tumor necrosis factor alpha) or by triggering death of infected cells through perforin- or fas ligand-dependent pathways. here, we directly evalu ...200616352536
identification and characterization of a penaeus monodon lymphoid cell-expressed receptor for the yellow head virus.the yellow head virus is a positive-sense, single-stranded rna virus that causes significant mortality in farmed penaeid shrimp. this study sought to isolate and characterize the receptor protein used by the virus to gain entry into penaeus monodon oka (lymphoid) organ cells, a primary target of yellow head virus infections. virus overlay protein binding assay on oka organ membrane preparations identified a 65-kda protein, and antibodies raised against this protein inhibited virus entry in prima ...200616352551
viral transgenesis of embryonic cell cultures from the freshwater microcrustacean daphnia.the aim of this study was to determine whether a recombinant vesicular stomatitis virus (vsv) vector encoding a transgene could be used to infect and express a foreign gene in embryonic primary cell cultures derived from the freshwater microcrustacean daphnia, the most widely used ecotoxicological model organism. to facilitate the evaluation of gene transfer, a reproducible method for establishing primary cultures from daphnia embryonic tissues was developed. within 24 hr after infection, transg ...200616358270
direct pyrogenic input from prostaglandin ep3 receptor-expressing preoptic neurons to the dorsomedial hypothalamus.fever is induced by a neuronal mechanism in the brain. prostaglandin (pg) e2 acts as a pyrogenic mediator in the preoptic area (poa) probably through the ep3 subtype of pge receptor expressed on gabaergic neurons, and this pge2 action triggers neuronal pathways for sympathetic thermogenesis in peripheral effector organs including brown adipose tissue (bat). to explore pyrogenic efferent pathways from the poa, we determined projection targets of ep3 receptor-expressing poa neurons with a special ...200516367780
reovirus variants selected for resistance to ammonium chloride have mutations in viral outer-capsid protein sigma3.mammalian reoviruses are internalized into cells by receptor-mediated endocytosis. within the endocytic compartment, the viral outer capsid undergoes acid-dependent proteolysis resulting in removal of the sigma3 protein and proteolytic cleavage of the mu1/mu1c protein. ammonium chloride (ac) is a weak base that blocks disassembly of reovirus virions by inhibiting acidification of intracellular vacuoles. to identify domains in reovirus proteins that influence ph-sensitive steps in viral disassemb ...200616378970
heparin-binding and patterns of virulence for two recombinant strains of sindbis virus.e2 is an important determinant of sindbis virus neurovirulence. increased heparan sulfate (hs) binding is associated with rapid clearance of viremia and usually with decreased virulence. however, substitution of histidine for arginine at e2-157 (r157h) or glutamate for lysine at e2-159 (k159e) produces viruses with decreases in heparin-sepharose binding and increases in viremia but different levels of binding to hs-expressing cells and virulence phenotypes in newborn cd-1 mice (byrnes, a.p., gri ...200616380143
ube1l and protein isgylation are not essential for alpha/beta interferon signaling.the expression of ubiquitin-like modifier isg15 and its conjugation to target proteins are highly induced by interferon (ifn) stimulation and during viral and bacterial infections. however, the biological significance of this modification has not been clearly understood. to investigate the function of protein modification by isg15, we generated a mouse model deficient in ube1l, an isg15-activating enzyme. ube1l-/- mice did not produce isg15 conjugates but expressed free isg15 normally. isgylatio ...200616382139
single and multiple deletions in the transmembrane domain of the sindbis virus e2 glycoprotein identify a region critical for normal virus growth.sindbis virus is composed of two nested t = 4 icosahedral protein shells containing 240 copies each of three structural proteins: e1, e2, and capsid in a 1:1:1 stoichiometric ratio. e2 is a 423 amino acid glycoprotein with a membrane spanning domain 26 amino acids in length and a 33 amino acid cytoplasmic endodomain. the interaction of the endodomain with the nucleocapsid is an essential step in virus maturation and directs the formation of the outer protein shell as envelopment occurs. a previo ...200616387341
translational resistance of late alphavirus mrna to eif2alpha phosphorylation: a strategy to overcome the antiviral effect of protein kinase pkr.the double-stranded rna-dependent protein kinase (pkr) is one of the four mammalian kinases that phosphorylates the translation initiation factor 2alpha in response to virus infection. this kinase is induced by interferon and activated by double-stranded rna (dsrna). phosphorylation of eukaryotic initiation factor 2alpha (eif2alpha) blocks translation initiation of both cellular and viral mrna, inhibiting virus replication. to counteract this effect, most viruses express inhibitors that prevent ...200616391235
mapping the structure and function of the e1 and e2 glycoproteins in alphaviruses.the 9 a resolution cryo-electron microscopy map of sindbis virus presented here provides structural information on the polypeptide topology of the e2 protein, on the interactions between the e1 and e2 glycoproteins in the formation of a heterodimer, on the difference in conformation of the two types of trimeric spikes, on the interaction between the transmembrane helices of the e1 and e2 proteins, and on the conformational changes that occur when fusing with a host cell. the positions of various ...200616407066
jam-a-independent, antibody-mediated uptake of reovirus into cells leads to apoptosis.apoptosis plays a major role in the cytopathic effect induced by reovirus following infection of cultured cells and newborn mice. strain-specific differences in the capacity of reovirus to induce apoptosis segregate with the s1 and m2 gene segments, which encode attachment protein sigma1 and membrane penetration protein mu1, respectively. virus strains that bind to both junctional adhesion molecule-a (jam-a) and sialic acid are the most potent inducers of apoptosis. in addition to receptor bindi ...200616415003
palmitoylations on murine coronavirus spike proteins are essential for virion assembly and infectivity.coronavirus spike (s) proteins are palmitoylated at several cysteine residues clustered near their transmembrane-spanning domains. this is achieved by cellular palmitoyl acyltransferases (pats), which can modify newly synthesized s proteins before they are assembled into virion envelopes at the intermediate compartment of the exocytic pathway. to address the importance of these fatty acylations to coronavirus infection, we exposed infected cells to 2-bromopalmitate (2-bp), a specific pat inhibit ...200616415005
west nile virus discriminates between dc-sign and dc-signr for cellular attachment and infection.the c-type lectins dc-sign and dc-signr bind mannose-rich glycans with high affinity. in vitro, cells expressing these attachment factors efficiently capture, and are infected by, a diverse array of appropriately glycosylated pathogens, including dengue virus. in this study, we investigated whether these lectins could enhance cellular infection by west nile virus (wnv), a mosquito-borne flavivirus related to dengue virus. we discovered that dc-signr promoted wnv infection much more efficiently t ...200616415006
[detection of sindbis virus-specific nucleic acid with sybr green i real time pcr assay].to develop a rapid, specific and sensitive method for detecting sindbis virus (sinv) with sybr green i real time pcr.200516415993
dissection of a viral autoprotease elucidates a function of a cellular chaperone in proteolysis.replication of positive-strand rna viruses involves translation of polyproteins which are proteolytically processed into functional peptides. these maturation steps often involve virus-encoded autoproteases specialized in generating their own n or c termini. nonstructural protein 2 (ns2) of the pestivirus bovine viral diarrhea virus represents such an enzyme. bovine viral diarrhea virus ns2 creates in cis its own c terminus and thereby releases an essential viral replication factor. as a unique ...200616432213
time- and temperature-dependent activation of hepatitis c virus for low-ph-triggered entry.hepatitis c virus (hcv) is an important human pathogen associated with chronic liver disease. recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and infectious virus production have been developed. in this study, we used cell culture-produced infectious hcv to analyze the viral entry pathway into huh-7.5 cells. bafilomycin a1 and concanamycin a, inhibitors of vacuolar atpases, prevented hcv entry when they were present prior to infection and had mini ...200616439530
core protein of pestiviruses is processed at the c terminus by signal peptide peptidase.the core protein of pestiviruses is released from the polyprotein by viral and cellular proteinases. here we report on an additional intramembrane proteolytic step that generates the c terminus of the core protein. c-terminal processing of the core protein of classical swine fever virus (csfv) was blocked by the inhibitor (z-ll)(2)-ketone, which is specific for signal peptide peptidase (spp). the same effect was obtained by overexpression of the dominant-negative spp d(265)a mutant. the presence ...200616439547
structural characterization of the e2 glycoprotein from sindbis by lysine biotinylation and lc-ms/ms.sindbis is an alphavirus capable of infecting and replicating in both vertebrate and invertebrate hosts. mature sindbis virus particles consist of an inner capsid surrounded by a host-derived lipid bilayer, which in turn is surrounded by a protein shell consisting of the e1 and e2 glycoproteins. while a homolog of the e1 glycoprotein has been structurally characterized, the amount of structural data on the e2 glycoprotein is considerably less. in this study, the organization of the e2 glycoprote ...200616443253
rna secondary structure in the coding region of dengue virus type 2 directs translation start codon selection and is required for viral replication.dengue virus is a positive-strand rna virus and a member of the genus flavivirus, which includes west nile, yellow fever, and tick-borne encephalitis viruses. flavivirus genomes are translated as a single polyprotein that is subsequently cleaved into 10 proteins, the first of which is the viral capsid (c) protein. dengue virus type 2 (denv2) and other mosquito-borne flaviviruses initiate translation of c from a start codon in a suboptimal context and have multiple in-frame augs downstream. here, ...200616474125
a single amino acid substitution in the west nile virus nonstructural protein ns2a disables its ability to inhibit alpha/beta interferon induction and attenuates virus virulence in mice.alpha/beta interferons (ifn-alpha/beta) are key mediators of the innate immune response against viral infection. the ability of viruses to circumvent ifn-alpha/beta responses plays a crucial role in determining the outcome of infection. in a previous study using subgenomic replicons of the kunjin subtype of west nile virus (wnv(kun)), we demonstrated that the nonstructural protein ns2a is a major inhibitor of ifn-beta promoter-driven transcription and that a single amino acid substitution in ns2 ...200616474146
role of a conserved tripeptide in the endodomain of sindbis virus glycoprotein e2 in virus assembly and function.envelopment of sindbis virus (sv) at the plasma membrane begins with the interaction of the e2 glycoprotein endodomain with a hydrophobic cleft in the surface of the pre-assembled nucleocapsid. the driving force for this budding event is thought to reside in this virus type-specific association at the surface of the cell. the specific amino acids involved in this interaction have not been identified; however, it has been proposed that a conserved motif (tpy) at aa 398-400 in the e2 tail plays a ...200616476988
ampa receptor downscaling at the onset of alzheimer's disease pathology in double knockin mice.it is widely thought that alzheimer's disease (ad) begins as a malfunction of synapses, eventually leading to cognitive impairment and dementia. homeostatic synaptic scaling is a mechanism that could be crucial at the onset of ad but has not been examined experimentally. in this process, the synaptic strength of a neuron is modified so that the overall excitability of the cell is maintained. here, we investigate whether synaptic scaling mediated by l-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepro ...200616492745
functional analyses of gb virus b p13 protein: development of a recombinant gb virus b hepatitis virus with a p7 protein.gb virus b (gbv-b), which infects tamarins, is the virus most closely related to hepatitis c virus (hcv). hcv has a protein (p7) that is believed to form an ion channel. it is critical for viability. in vitro studies suggest that gbv-b has an analogous but larger protein (p13). we found that substitutions of the -1 and/or -3 residues of the putative cleavage sites (amino acid 613/614 and 732/733) abolished processing in vitro and rendered an infectious gbv-b clone nonviable in tamarins. internal ...200616492760
replication and clearance of venezuelan equine encephalitis virus from the brains of animals vaccinated with chimeric sin/vee viruses.venezuelan equine encephalitis virus (veev) is an important, naturally emerging zoonotic pathogen. recent outbreaks in venezuela and colombia in 1995, involving an estimated 100,000 human cases, indicate that veev still poses a serious public health threat. to develop a safe, efficient vaccine that protects against disease resulting from veev infection, we generated chimeric sindbis (sin) viruses expressing structural proteins of different strains of veev and analyzed their replication in vitro ...200616501087
a single codon in the nucleocapsid protein c terminus contributes to in vitro and in vivo fitness of edmonston measles virus.the major inducible 70-kda heat shock protein (hsp72) increases measles virus (mv) transcription and genome replication. this stimulatory effect is attributed to hsp72 interaction with two highly conserved hydrophobic domains in the nucleocapsid protein (n) c terminus of edmonston mv. these domains are known as box-2 and box-3. a single amino acid substitution in box-3 of edmonston mv (i.e., n522d) disrupts hsp72 binding. the prevalence of the n522d substitution in contemporary wild-type mv isol ...200616501099
rnase l plays a role in the antiviral response to west nile virus.alleles at the flv locus determine disease outcome after a flavivirus infection in mice. although comparable numbers of congenic resistant and susceptible mouse embryo fibroblasts (mefs) are infected by the flavivirus west nile virus (wnv), resistant mefs produce approximately 100- to 150-fold lower titers than susceptible ones and flavivirus titers in the brains of resistant and susceptible animals can differ by >10,000-fold. the flv locus was previously identified as the 2'-5' oligoadenylate s ...200616501108
identification of mutations causing temperature-sensitive defects in semliki forest virus rna synthesis.we have sequenced the nonstructural protein coding region of semliki forest virus temperature-sensitive (ts) mutant strains ts1, ts6, ts9, ts10, ts11, ts13, and ts14. in each case, the individual amino acid changes uncovered were transferred to the prototype strain background and thereby identified as the underlying cause of the altered rna synthesis phenotype. all mutations mapping to the protease domain of nonstructural protein nsp2 caused defects in nonstructural polyprotein processing and su ...200616501123
sindbis virus as a tool for quality control of viral inactivation of heated and chemically treated plasma-derived products.regulatory guidelines for production of plasma-derived products emphasize the need to document methods of viral inactivation and demonstrate the effectiveness of screening methods. therefore, it is important to evaluate the kinetics of such processes. togaviridae family virions may be considered as good tools for quality control of haemoderivatives, if they possess large amounts of cholesterol and saturated lipids and high structural lipid/protein ratio in their envelope composition, which give ...200616507321
high-dose gamma irradiation for soft tissue allografts: high margin of safety with biomechanical integrity.screening and processing methods currently in place have made the risk of bacterial and viral infections from allograft tissues extremely low. however, the development of a terminal sterilization method that does not adversely affect tissue function would provide an added safety to tissues for transplantation. we assessed whether high-dose gamma irradiation could be used as an effective terminal sterilization method for allografts without impairing the preimplantation mechanical integrity of the ...200616514624
a colorimetric assay for viral agents that produce cytopathic effects.many animal viruses produce cytopathic effects in their host cells during a productive infection. while some virus infections can be assayed by the production of plaques, many viruses, while producing cytotoxicity, do not easily form plaques, or do not form plaques at all. additionally, viruses within families such as the parvoviruses may have different preferred forms of titration making comparative virology difficult even among related groups. porcine parvovirus (ppv), canine parvovirus (cpv), ...200616516983
nonstructural protein of infectious bursal disease virus inhibits apoptosis at the early stage of virus infection.infectious bursal disease virus (ibdv), the causative agent of a highly contagious disease in chickens, carries a small nonstructural protein (ns). this protein has been implicated to play a role in the induction of apoptosis. in this study, we investigate the kinetics of viral replication during a single round of viral replication and examine the mechanism of ibdv-induced apoptosis. our results show that it is caspase dependent and activates caspases 3 and 9. nuclear factor kappa b (nf-kappab) ...200616537604
mutagenesis analysis of the nsp4 main proteinase reveals determinants of arterivirus replicase polyprotein autoprocessing.nonstructural protein 4 (nsp4; 204 amino acids) is the chymotrypsin-like serine main proteinase of the arterivirus equine arteritis virus (order nidovirales), which controls the maturation of the replicase complex. nsp4 includes a unique c-terminal domain (ctd) connected to the catalytic two-beta-barrel structure by the poorly conserved residues 155 and 156. this dipeptide might be part of a hinge region (hr) that facilitates interdomain movements and thereby regulates (in time and space) autopr ...200616537610
porcine circovirus 2 uses heparan sulfate and chondroitin sulfate b glycosaminoglycans as receptors for its attachment to host cells.monocyte/macrophage lineage cells are target cells in vivo for porcine circovirus 2 (pcv2) replication. the porcine monocytic cell line 3d4/31 supports pcv2 replication in vitro, and attachment and internalization kinetics of pcv2 have been established in these cells. however, pcv2 receptors remain unknown. glycosaminoglycans (gag) are used by several viruses as receptors. the present study examined the role of gag in attachment and infection of pcv2. heparin, heparan sulfate (hs), chondroitin s ...200616537616
rab22a regulates the sorting of transferrin to recycling endosomes.rab22a is a member of the rab family of small gtpases that localizes in the endocytic pathway. in cho cells, expression of canine rab22a (crab22a) causes a dramatic enlargement of early endocytic compartments. we wondered whether transferrin recycling is altered in these cells. expression of the wild-type protein and a gtp hydrolysis-deficient mutant led to the redistribution of transferrin receptor to large crab22a-positive structures in the periphery of the cell and to a significant decrease i ...200616537905
essential function in vivo for dicer-2 in host defense against rna viruses in drosophila.the fruit fly drosophila melanogaster is a model system for studying innate immunity, including antiviral host defense. infection with drosophila c virus triggers a transcriptional response that is dependent in part on the jak kinase hopscotch. here we show that successful infection and killing of drosophila with the insect nodavirus flock house virus was strictly dependent on expression of the viral protein b2, a potent inhibitor of processing of double-stranded rna mediated by the essential rn ...200616554838
[use of getah virus for antiviral assay of human interferon].antiviral assay is used routinely for measuring the biological activity of interferon (ifn). however, the challenge viruses used in these assays are considered dangerous to the animal industry and pose a risk of human infection. for example, the vesicular stomatitis virus (vsv) is an important exotic disease agent in domestic animals, and the sindbis virus provokes rash, arthralgia, and fever in humans. therefore, biosafety needs to be considered when antiviral assays are performed. we chose get ...200516557019
age-dependent resistance of mice to sindbis virus infection: viral replication as a function of host age.the development of resistance of outbred white mice to two plaque size variants of sindbis virus was studied as a function of host age. a sudden drop in mortality occurred over a 3-day period. as little as 1 plaque-forming unit (pfu) per mouse was lethal in 1-day-old animals, whereas inocula of 10(9) pfu per mouse failed to produce high mortality in weanlings. a comparison of viral growth kinetics shows that early replication was similar in newborns and weanlings but that after 6 to 8 hr the pro ...197116557964
testosterone correlates with venezuelan equine encephalitis virus infection in macaques.here we briefly report testosterone and cytokine responses to venezuelan equine encephalitis virus (veev) in macaques which were used as part of a larger study conducted by the department of defense to better characterize pathological responses to aerosolized veev in non-human primates. serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. infected animals exhibited a febrile response with few significant changes in cy ...200616571136
hippocampal long-term potentiation is supported by presynaptic and postsynaptic tyrosine receptor kinase b-mediated phospholipase cgamma signaling.neurotrophins have been shown to play a critical role in activity-dependent synaptic plasticity such as long-term potentiation (ltp) in the hippocampus. although the role of brain-derived neurotrophic factor (bdnf) and its tyrosine kinase receptor [tyrosine receptor kinase b (trkb)] is well documented, it still remains unresolved whether presynaptic or postsynaptic activation of trkb is involved in the induction of ltp. to address this question, we locally and specifically interfered with a down ...200616571757
recovery of a recombinant salmonid alphavirus fully attenuated and protective for rainbow trout.sleeping disease virus (sdv) is a member of the new salmonid alphavirus genus within the togaviridae family. the single-stranded rna genome of sdv is 11,894 nucleotides long, excluding the 3' poly(a) tail. a full-length cdna has been generated; the cdna was fused to a hammerhead ribozyme sequence at the 5' end and inserted into a transcription plasmid (pcdna3) backbone, yielding psdv. by transfection of psdv into fish cells, recombinant sdv (rsdv) was successfully recovered. demonstration of the ...200616571825
formation of nsp3-specific protein complexes during sindbis virus replication.alphaviruses are arthropod-borne viruses (arboviruses) that include a number of important human and animal pathogens. their replication proceeds in the cytoplasm of infected cells and does not directly depend on nuclei. alphaviruses encode only four nonstructural proteins that are required for the replication of viral genome and transcription of the subgenomic rna. however, the replicative enzyme complexes (rcs) appear to include cellular proteins and assemble on cellular organelles. we have dev ...200616571828
hiv protease cleaves poly(a)-binding protein.the pabp [poly(a)-binding protein] is able to interact with the 3' poly(a) tail of eukaryotic mrna, promoting its translation. cleavage of pabp by viral proteases encoded by several picornaviruses and caliciviruses plays a role in the abrogation of cellular protein synthesis. we report that infection of mt-2 cells with hiv-1 leads to efficient proteolysis of pabp. analysis of pabp integrity was carried out in bhk-21 (baby-hamster kidney) and cos-7 cells upon individual expression of the protease ...200616594896
combining caspase and mitochondrial dysfunction inhibitors of apoptosis to limit cell death in mammalian cell cultures.apoptosis is now recognized as a significant problem in mammalian cell culture. therefore, in this study, a single gene and multigene approach to inhibit apoptosis has been examined. stable chinese hamster ovary (cho) cell lines were generated to overexpress different single, dual, and triple combinations of three apoptosis inhibitor genes. two upstream inhibitors involved in the mitochondrial pathway, bcl-x(l) and aven, were expressed in addition to a downstream inhibitor of caspases. the caspa ...200616598795
antiviral effect of the mammalian translation initiation factor 2alpha kinase gcn2 against rna viruses.in mammals, four different protein kinases, heme-regulated inhibitor, double-stranded rna-dependent protein kinase (pkr), general control non-derepressible-2 (gcn2) and pkr-like endoplasmic reticulum kinase, regulate protein synthesis in response to environmental stresses by phosphorylating the alpha-subunit of the initiation factor 2 (eif2alpha). we now report that mammalian gcn2 is specifically activated in vitro upon binding of two nonadjacent regions of the sindbis virus (sv) genomic rna to ...200616601681
dual role of the exocyst in ampa receptor targeting and insertion into the postsynaptic membrane.intracellular membrane trafficking of glutamate receptors at excitatory synapses is critical for synaptic function. however, little is known about the specialized trafficking events occurring at the postsynaptic membrane. we have found that two components of the exocyst complex, sec8 and exo70, separately control synaptic targeting and insertion of ampa-type glutamate receptors. sec8 controls the directional movement of receptors towards synapses through pdz-dependent interactions. in contrast, ...200616601687
gene therapy that safely targets and kills tumor cells throughout the body.the authors studied the therapeutic value of sindbis vectors for advanced metastatic cancer by using a variety of clinically accurate mouse models and demonstrated through imaging, histological, and molecular data that sindbis vectors systemically and specifically infect/detect and kill metastasized tumors in vivo, leading to significant suppression of tumor growth and enhanced survival. use of two different bioluminescent genetic markers for the ivis imaging system (xenogen corp., alameda, ca) ...200616608394
repair and polyadenylation of a naturally occurring hepatitis c virus 3' nontranslated region-shorter variant in selectable replicon cell lines.the 3' nontranslated region (ntr) of the hepatitis c virus (hcv) genome is highly conserved and contains specific cis-acting rna motifs that are essential in directing the viral replication machinery to initiate at the correct 3' end of the viral genome. since the ends of viral genomes may be damaged by cellular rnases, preventing the initiation of viral rna replication, stable rna hairpin structures in the 3' ntr may also be essential in host defense against exoribonucleases. during 3'-terminal ...200616611892
mutations in the endodomain of sindbis virus glycoprotein e2 define sequences critical for virus assembly.envelopment of sindbis virus at the plasma membrane is a multistep process in which an initial step is the association of the e2 protein via a cytoplasmic endodomain with the preassembled nucleocapsid. sindbis virus is vectored in nature by blood-sucking insects and grows efficiently in a number of avian and mammalian vertebrate hosts. the assembly of sindbis virus, therefore, must occur in two very different host cell environments. mammalian cells contain cholesterol which insect membranes lack ...200616611906
neonatal immunization with a sindbis virus-dna measles vaccine induces adult-like neutralizing antibodies and cell-mediated immunity in the presence of maternal antibodies.infants younger than age 9 mo do not respond reliably to the live attenuated measles vaccine due the immaturity of their immune system and the presence of maternal abs that interfere with successful immunization. we evaluated the immune responses elicited by sindbis virus replicon-based dna vaccines encoding measles virus (mv) hemagglutinin (h, pmsin-h) or both hemagglutinin and fusion (f, pmsinh-fdu) glycoproteins in neonatal mice born to naive and measles-immune mothers. despite the presence o ...200616622037
partial reconstitution of the cd4+-t-cell compartment in cd4 gene knockout mice restores responses to tuberculosis dna vaccines.reactivation tuberculosis (tb) is a serious problem in immunocompromised individuals, especially those with human immunodeficiency virus (hiv) coinfection. the adaptive immune response mediated by cd4+ and cd8+ t cells is known to confer protection against tb. hence, vaccines against tb are designed to activate these two components of the immune system. anti-tb dna vaccines encoding the immunodominant proteins ag85a, ag85b, and psts-3 from mycobacterium tuberculosis are ineffective in mice lacki ...200616622212
[detection of banna virus-specific nucleic acid with taqman rt-pcr assay].to develop a rapid and more sensitive taqman rt-pcr assay specific for banna virus.200616642219
sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity.alphavirus vectors have emerged as a promising strategy for the development of cancer vaccines and gene therapy applications. in this study, we used the replication-defective vaccine vector sin replicon particles from a new packaging cell line (pcl) to develop sin replicon particles encoding calreticulin (crt) linked to a model tumor antigen, human papillomavirus type 16 (hpv16) e7 protein. the linkage of crt to e7 in sin replicon particles resulted in a significant increase in e7-specific cd8(+ ...200616645621
bioportfolio: lifelong persistence of variant and prototypic erythrovirus dna genomes in human tissue.human erythrovirus is a minute, single-stranded dna virus causing many diseases, including erythema infectiosum, arthropathy, and fetal death. after primary infection, the viral genomes persist in solid tissues. besides the prototype, virus type 1, two major variants (virus types 2 and 3) have been identified recently, the clinical significance and epidemiology of which are mostly unknown. we examined 523 samples of skin, synovium, tonsil, or liver (birth year range, 1913-2000), and 1,640 sera, ...200616651522
induction of apoptosis limits cytomegalovirus cross-species infection.cross-species infections are responsible for the majority of emerging and re-emerging viral diseases. however, little is known about the mechanisms that restrict viruses to a certain host species, and the factors viruses need to cross the species barrier and replicate in a different host. cytomegaloviruses (cmvs) are representatives of the beta-herpesviruses that are highly species specific. they replicate only in cells of their own or a closely related species. in this study, the molecular mech ...200616688216
altered immune response to cns viral infection in mice with a conditional knock-down of macrophage-lineage cells.neuroadapted sindbis virus (nsv) is a neuronotropic virus that causes hindlimb paralysis in susceptible mice and rats. the authors and others have demonstrated that though death of infected motor neurons occurs, bystander death of uninfected neurons also occurs and both contribute to the paralysis that ensues following infection. the authors have previously shown that the treatment of nsv-infected mice with minocycline, an inhibitor that has many functions within the central nervous system (cns) ...200616691560
gamma interferon plays a crucial early antiviral role in protection against west nile virus infection.west nile virus (wnv) causes a severe central nervous system (cns) infection in humans, primarily in the elderly and immunocompromised. prior studies have established an essential protective role of several innate immune response elements, including alpha/beta interferon (ifn-alpha/beta), immunoglobulin m, gammadelta t cells, and complement against wnv infection. in this study, we demonstrate that a lack of ifn-gamma production or signaling results in increased vulnerability to lethal wnv infect ...200616699014
molecular determinants of substrate specificity for semliki forest virus nonstructural protease.the c-terminal cysteine protease domain of semliki forest virus nonstructural protein 2 (nsp2) regulates the virus life cycle by sequentially cleaving at three specific sites within the virus-encoded replicase polyprotein p1234. the site between nsp3 and nsp4 (the 3/4 site) is cleaved most efficiently. analysis of semliki forest virus-specific cleavage sites with shuffled n-terminal and c-terminal half-sites showed that the main determinants of cleavage efficiency are located in the region prece ...200616699022
a herpes simplex virus recombinant that exhibits a single-chain antibody to her2/neu enters cells through the mammary tumor receptor, independently of the gd receptors.the human epidermal growth factor receptor 2/neuregulin (her2/neu) receptor is overexpressed in highly malignant mammary and ovarian tumors and correlates with a poor prognosis. it is a target for therapy; humanized monoclonal antibodies to her2 have led to increased survival of patients with her2/neu-positive breast cancer. as a first step in the design of an oncolytic herpes simplex virus able to selectively infect her2/neu-positive cells, we constructed two recombinants, r-lm11 and r-lm11l, t ...200616699034
genome microevolution of chikungunya viruses causing the indian ocean outbreak.a chikungunya virus outbreak of unprecedented magnitude is currently ongoing in indian ocean territories. in réunion island, this alphavirus has already infected about one-third of the human population. the main clinical symptom of the disease is a painful and invalidating poly-arthralgia. besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed severe clinical signs, i.e., neurological signs or fulminant hepatitis.200616700631
phosphatidylserine is involved in gene expression from sindbis virus subgenomic promoter.sindbis virus replication is mediated by an rna replicase translated from viral rna genome. the replicase synthesizes progeny genomic rna and shorter rna (subgenomic rna) carrying viral structural genes in association with cytoplasmic membranes. here we examined the involvement of a membrane lipid, phosphatidylserine (ps), in sindbis virus gene expression using chinese hamster ovary cell mutants. when the mutant cells were transfected with viral replicon rna, in which the structural genes downst ...200616701551
potential arbovirus emergence and implications for the united kingdom.arboviruses have evolved a number of strategies to survive environmental challenges. this review examines the factors that may determine arbovirus emergence, provides examples of arboviruses that have emerged into new habitats, reviews the arbovirus situation in western europe in detail, discusses potential arthropod vectors, and attempts to predict the risk for arbovirus emergence in the united kingdom. we conclude that climate change is probably the most important requirement for the emergence ...200616704800
ubp43 is a novel regulator of interferon signaling independent of its isg15 isopeptidase activity.interferons (ifns) regulate diverse cellular functions through activation of the janus kinase-signal transducer and activator of transcription (jak-stat) pathway. lack of ubp43, an ifn-inducible isg15 deconjugating enzyme, leads to ifn hypersensitivity in ubp43-/- mice, suggesting an important function of ubp43 in downregulation of ifn responses. here, we show that ubp43 negatively regulates ifn signaling independent of its isopeptidase activity towards isg15. ubp43 functions specifically for ty ...200616710296
production and characterization of vaccines based on flaviviruses defective in replication.to develop new vaccine candidates for flavivirus infections, we have engineered two flaviviruses, yellow fever virus (yfv) and west nile virus (wnv), that are deficient in replication. these defective pseudoinfectious viruses (pivs) lack a functional copy of the capsid (c) gene in their genomes and are incapable of causing spreading infection upon infection of cells both in vivo and in vitro. however, they produce extracellular e protein in form of secreted subviral particles (svps) that are kno ...200616712897
partial beclin 1 silencing aggravates doxorubicin- and fas-induced apoptosis in hepg2 cells.to investigate the role of beclin 1 on the susceptibility of hepg2 cells to undergo apoptosis after anti-fas antibody or doxorubicin treatment.200616718815
type i interferons are essential for the efficacy of replicase-based dna vaccines.the immunogenicity and efficacy of nucleic acid vaccines can be greatly enhanced when antigen production is under the control of an alphaviral replicase enzyme. however, replicase-mediated mrna overproduction does not necessarily result in enhanced antigen level. instead, the strong adaptive immune response of alphavirus replicon-based vectors is due to their production of double-stranded rna (dsrna) intermediates, which trigger innate immunity. because viral infections are known to trigger inna ...200616725231
sindbis virus nonstructural protein nsp2 is cytotoxic and inhibits cellular transcription.replication of alphaviruses in vertebrate cells strongly affects cell physiology and ultimately leads to development of a cytopathic effect (cpe) and cell death. sindbis virus (sin) replication causes major changes in cellular macromolecular synthesis, in which the strong downregulation of transcription of cellular mrnas and rrnas plays a critical role. sin nonstructural protein nsp2 was previously proposed as one of the main regulators of virus-host cell interactions, because point mutations in ...200616731907
blocking of interferon-induced jak-stat signaling by japanese encephalitis virus ns5 through a protein tyrosine phosphatase-mediated mechanism.japanese encephalitis virus (jev), a mosquito-borne flavivirus that causes severe human disease, has been shown to block the interferon (ifn)-induced janus kinase signal transducer and activation of transcription (jak-stat) signaling cascade by preventing tyk2 tyrosine phosphorylation and stat activation. in this study, we demonstrate that expression of the jev nonstructural protein ns5 readily blocked ifn-stimulated jak-stat signaling events such as stat1 nuclear translocation and tyrosine phos ...200616731929
polyadenylation of genomic rna and initiation of antigenomic rna in a positive-strand rna virus are controlled by the same cis-element.genomes and antigenomes of many positive-strand rna viruses contain 3'-poly(a) and 5'-poly(u) tracts, respectively, serving as mutual templates. mechanism(s) controlling the length of these homopolymeric stretches are not well understood. here, we show that in coxsackievirus b3 (cvb3) and three other enteroviruses the poly(a) tract is approximately 80-90 and the poly(u) tract is approximately 20 nt-long. mutagenesis analysis indicate that the length of the cvb3 3'-poly(a) is determined by the or ...200616738134
tau aggregation and progressive neuronal degeneration in the absence of changes in spine density and morphology after targeted expression of alzheimer's disease-relevant tau constructs in organotypic hippocampal slices.alzheimer's disease (ad) is characterized by progressive loss of neurons in selected brain regions, extracellular accumulations of amyloid beta, and intracellular fibrils containing hyperphosphorylated tau. tau mutations in familial tauopathies confirmed a central role of tau pathology; however, the role of tau alteration and the sequence of tau-dependent neurodegeneration in ad remain elusive. using sindbis virus-mediated expression of ad-relevant tau constructs in hippocampal slices, we show t ...200616738255
regulation of inducible nitric oxide synthase gene in glial cells.elevated levels of no produced within the central nervous system (cns) are associated with the pathogenesis of neuroinflammatory and neurodegenerative human diseases such as multiple sclerosis, hiv dementia, brain ischemia, trauma, parkinson's disease, and alzheimer's disease. resident glial cells in the cns (astroglia and microglia) express inducible nitric oxide synthase (inos) and produce high levels of no in response to a wide variety of proinflammatory and degenerative stimuli. although pat ...200616771683
suppression of the interferon-mediated innate immune response by pseudorabies virus.pseudorabies virus (prv) is an alphaherpesvirus related to the human pathogens herpes simplex virus type 1 (hsv-1) and varicella-zoster virus. prv is capable of infecting and killing a wide variety of mammals. how it avoids innate immune defenses in so many hosts is not understood. while the anti-interferon (ifn) strategies of hsv-1 have been studied, little is known about how prv evades the ifn-mediated immune response. in this study, we determined if wild-type prv infection can overcome the es ...200616775323
x-ray structures of the n- and c-terminal domains of a coronavirus nucleocapsid protein: implications for nucleocapsid formation.coronaviruses cause a variety of respiratory and enteric diseases in animals and humans including severe acute respiratory syndrome. in these enveloped viruses, the filamentous nucleocapsid is formed by the association of nucleocapsid (n) protein with single-stranded viral rna. the n protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signaling pathways. we describe the structure of the two proteolytically resistant domains of the n p ...200616775348
morphology of bhk-21 cells infected with sindbis virus temperature-sensitive mutants in complementation groups d and e.bhk-21 cells infected with temperature-sensitive mutants of sindbis virus in complementation groups d and e differed in their appearance under nonpermissive conditions. cells infected at nonpermissive temperature with virus defective in complementation group e had nucleocapsids attached in large numbers to the inside surface of the host plasma membrane. infection with a group d mutant produced nucleocapsids that did not attach to the plasma membrane but rather remained free in the cell cytoplasm ...197516789157
novel putative targets of n-ethylmaleimide sensitive fusion protein (nsf) and alpha/beta soluble nsf attachment proteins (snaps) include the pak-binding nucleotide exchange factor betapix.n-ethylmaleimide sensitive fusion protein (nsf) is a chaperone that plays a crucial role in the fusion of vesicles with target membranes. nsf mediates the atp-consuming dissociation of a core protein complex that assembles during vesicle fusion and it thereby recharges the fusion machinery to perform multiple rounds of fusion. the binding of nsf to the core complex is mediated by co-chaperones named soluble nsf attachment proteins (snaps), for which three isoforms (alpha, beta and gamma) are kno ...200616795052
hepatitis c virus entry depends on clathrin-mediated endocytosis.due to difficulties in cell culture propagation, the mechanisms of hepatitis c virus (hcv) entry are poorly understood. here, postbinding cellular mechanisms of hcv entry were studied using both retroviral particles pseudotyped with hcv envelope glycoproteins (hcvpp) and the hcv clone jfh-1 propagated in cell culture (hcvcc). hcvpp entry was measured by quantitative real-time pcr after 3 h of contact with target cells, and hcvcc infection was quantified by immunoblot analysis and immunofluoresce ...200616809302
pkr and rnase l contribute to protection against lethal west nile virus infection by controlling early viral spread in the periphery and replication in neurons.west nile virus (wnv) is a neurotropic, mosquito-borne flavivirus that can cause lethal meningoencephalitis. type i interferon (ifn) plays a critical role in controlling wnv replication, spread, and tropism. in this study, we begin to examine the effector mechanisms by which type i ifn inhibits wnv infection. mice lacking both the interferon-induced, double-stranded-rna-activated protein kinase (pkr) and the endoribonuclease of the 2',5'-oligoadenylate synthetase-rnase l system (pkr(-/-) x rl(-/ ...200616809306
prime-boost immunization using dna vaccine and recombinant orf virus protects pigs against pseudorabies virus (herpes suid 1).the present study demonstrates the protective potential of a novel prime-boost vaccination strategy of pigs against lethal pseudorabies virus (prv; herpes suid 1) infection. animals were primed with sindbis virus-derived plasmids that express viral glycoproteins gc and gd (gc- and gd-psin) and subsequently booster immunized with orf virus (orfv; parapoxvirus) recombinants expressing gc and gd (d1701-vrvgc and -vrvgd). the prime-boost vaccination induced strong humoral and cellular-like prv-speci ...200616814432
tumor-specific in vivo transfection with hsv-1 thymidine kinase gene using a sindbis viral vector as a basis for prodrug ganciclovir activation and pet.one type of gene therapy of tumors, gene-directed enzyme-prodrug therapy (gdept), holds considerable promise, although practical considerations limit its clinical applicability. these include the lack of acceptable noninvasive methods that are adaptable to humans for selective tumor targeting of the therapeutic genetic material. sindbis virus is an oncolytic, alpha-virus that selectively targets tumors through the 67-kda laminin receptor (lamr). in this report we describe a novel approach that p ...200616818948
maintenance of cd8 effector t cells by cd4 helper t cells eradicates growing tumors and promotes long-term tumor immunity.human papillomavirus, particularly type 16 (hpv-16), is present in more than 99% of cervical cancers, and oncogenic hpv infection is one of the most important etiologies. it is now clear that cd4(+) t cells play an important role in controlling hpv-associated lesions because immunocompromised patients have a higher frequency of hpv-associated lesions. in the current study, we characterized the significance of cd4(+) t cells in the generation of e7-specific cd8(+) t cell immune responses in mice ...200616824651
epitope-blocking enzyme-linked immunosorbent assay for detection of antibodies to ross river virus in vertebrate sera.we describe the development of an epitope-blocking enzyme-linked immunosorbent assay (elisa) for the sensitive and rapid detection of antibodies to ross river virus (rrv) in human sera and known vertebrate host species. this elisa provides an alternative method for the serodiagnosis of rrv infections.200616829622
carrageenan is a potent inhibitor of papillomavirus infection.certain sexually transmitted human papillomavirus (hpv) types are causally associated with the development of cervical cancer. our recent development of high-titer hpv pseudoviruses has made it possible to perform high-throughput in vitro screens to identify hpv infection inhibitors. comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted hpvs. ...200616839203
entry of feline calicivirus is dependent on clathrin-mediated endocytosis and acidification in endosomes.feline calicivirus is a major causative agent of respiratory disease in cats. it is also one of the few cultivatable members of caliciviridae. we have examined the entry process of feline calicivirus (fcv). an earlier study demonstrated that acidification in endosomes may be required. we have confirmed this observation and expanded upon it, demonstrating, using drugs to inhibit the various endocytic pathways and dominant-negative mutants, that fcv infects cells via clathrin-mediated endocytosis. ...200616840330
newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death.newcastle disease virus (ndv), an avian paramyxovirus, is tumor selective and intrinsically oncolytic. here, we present evidence that genetically modified, recombinant ndv strains are cytotoxic to human tumor cell lines of ecto-, endo-, and mesodermal origin. we show that cytotoxicity against tumor cells is due to multiple caspase-dependent pathways of apoptosis independent of interferon signaling competence. the signaling pathways of ndv-induced, cancer cell-selective apoptosis are not well und ...200616840332
ribosomal protein s6 associates with alphavirus nonstructural protein 2 and mediates expression from alphavirus messages.although alphaviruses dramatically alter cellular function within hours of infection, interactions between alphaviruses and specific host cellular proteins are poorly understood. although the alphavirus nonstructural protein 2 (nsp2) is an essential component of the viral replication complex, it also has critical auxiliary functions that determine the outcome of infection in the host. to gain a better understanding of nsp2 function, we sought to identify cellular proteins with which venezuelan e ...200616840351
utilization of host sr protein kinases and rna-splicing machinery during viral replication.although the viral genome is often quite small, it encodes a broad series of proteins. the virus takes advantage of the host-rna-processing machinery to provide the alternative splicing capability necessary for the expression of this proteomic diversity. serine-arginine-rich (sr) proteins and the kinases that activate them are central to this alternative splicing machinery. in studies reported here, we use the hiv genome as a model. we show that hiv expression decreases overall sr protein/activi ...200616840555
bats: important reservoir hosts of emerging viruses.bats (order chiroptera, suborders megachiroptera ["flying foxes"] and microchiroptera) are abundant, diverse, and geographically widespread. these mammals provide us with resources, but their importance is minimized and many of their populations and species are at risk, even threatened or endangered. some of their characteristics (food choices, colonial or solitary nature, population structure, ability to fly, seasonal migration and daily movement patterns, torpor and hibernation, life span, roo ...200616847084
cryptosporidium parvum infects human cholangiocytes via sphingolipid-enriched membrane microdomains.cryptosporidium parvum attaches to intestinal and biliary epithelial cells via specific molecules on host-cell surface membranes including gal/galnac-associated glycoproteins. subsequent cellular entry of this parasite depends on host-cell membrane alterations to form a parasitophorous vacuole via activation of phosphatidylinositol 3-kinase (pi-3k)/cdc42-associated actin remodelling. how c. parvum hijacks these host-cell processes to facilitate its infection of target epithelia is unclear. using ...200616848787
sindbis virus infection of two model insect cell systems--a comparative study.sindbis, the prototype of the alphaviruses causes mosquito-borne diseases in mammals and replicates in a wide variety of vertebrate and invertebrate cell cultures. this characteristic can be exploited to use the vast array of drosophila genetic information available for investigations of the interaction of sindbis virus with an alternate invertebrate host. for this purpose, a comparative study of sindbis virus infection of schnieder-2 drosophila (s2) cells to cells of the mosquito aedes albopict ...200616854488
a 5' rna element promotes dengue virus rna synthesis on a circular genome.the mechanisms of rna replication of plus-strand rna viruses are still unclear. here, we identified the first promoter element for rna synthesis described in a flavivirus. using dengue virus as a model, we found that the viral rdrp discriminates the viral rna by specific recognition of a 5' element named sla. we demonstrated that rna-rna interactions between 5' and 3' end sequences of the viral genome enhance dengue virus rna synthesis only in the presence of an intact sla. we propose a novel me ...200616882970
hiv and cxcr4 in a kiss of autophagic death.aids is characterized by cd4+ t lymphocyte depletion, yet the mechanisms underlying this central aspect of hiv pathogenesis are still poorly understood. in this issue of the jci, espert et al. identify a mechanism by which the hiv envelope glycoprotein can induce death in uninfected cd4+ t cells (see the related article beginning on page 2161). the hiv envelope glycoprotein interacts with cxc chemokine receptor 4 to activate the lysosomal degradation pathway of autophagy, which is necessary for ...200616886053
autophagy is involved in t cell death after binding of hiv-1 envelope proteins to cxcr4.hiv-1 envelope glycoproteins (env), expressed at the cell surface, induce apoptosis of uninfected cd4+ t cells, contributing to the development of aids. here we demonstrate that, independently of hiv replication, transfected or hiv-infected cells that express env induced autophagy and accumulation of beclin 1 in uninfected cd4+ t lymphocytes via cxcr4. the same phenomena occurred in a t cell line and in transfected hek.293 cells that expressed both wild-type cxcr4 and a truncated form of cd4 tha ...200616886061
possible ecology and epidemiology of medically important mosquito-borne arboviruses in great britain.nine different arboviruses are known to be transmitted by, or associated with, mosquitoes in europe, and several (west nile, sindbis and tahyna viruses) are reported to cause outbreaks of human disease. although there have been no reported human cases in great britain (gb), there have been no published in-depth serological surveys for evidence of human infection. this paper investigates the ecological and entomological factors that could influence or restrict transmission of these viruses in gb, ...200716893487
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