| autophagy and checkpoints for intracellular pathogen defense. | autophagy plays a crucial role in intracellular defense against various pathogens. xenophagy is a form of selective autophagy that targets intracellular pathogens for degradation. in addition, several related, yet distinct, intracellular defense responses depend on autophagy-related genes. this review gives an overview of these processes, pathogen strategies to subvert them, and their crosstalk with various cell death programs. | 0 | 25394238 |
| the combined use of alphavirus replicons and pseudoinfectious particles for the discovery of antivirals derived from natural products. | alphaviruses are a prominent class of reemergent pathogens due to their globally expanding ranges, potential for lethality, and possible use as bioweapons. the absence of effective treatments for alphaviruses highlights the need for innovative strategies to identify antiviral agents. primary screens that use noninfectious self-replicating rnas, termed replicons, have been used to identify potential antiviral compounds for alphaviruses. only inhibitors of viral genome replication, however, will b ... | 2014 | 25550354 |
| antiviral immunity of anopheles gambiae is highly compartmentalized, with distinct roles for rna interference and gut microbiota. | arboviruses are transmitted by mosquitoes and other arthropods to humans and animals. the risk associated with these viruses is increasing worldwide, including new emergence in europe and the americas. anopheline mosquitoes are vectors of human malaria but are believed to transmit one known arbovirus, o'nyong-nyong virus, whereas aedes mosquitoes transmit many. anopheles interactions with viruses have been little studied, and the initial antiviral response in the midgut has not been examined. he ... | 2014 | 25548172 |
| upon intranasal vesicular stomatitis virus infection, astrocytes in the olfactory bulb are important interferon beta producers that protect from lethal encephalitis. | previously we found that following intranasal (i.n.) infection with neurotropic vesicular stomatitis virus (vsv) type i interferon receptor (ifnar) triggering of neuroectodermal cells was critically required to constrain intracerebral virus spread. to address whether locally active ifn-β was induced proximally, we studied spatiotemporal conditions of vsv-mediated ifn-β induction. to this end, we performed infection studies with ifn-β reporter mice. one day after intravenous (i.v.) vsv infection, ... | 2014 | 25540366 |
| deficiency in either 4e-bp1 or 4e-bp2 augments innate antiviral immune responses. | genetic deletion of both 4e-bp1 and 4e-bp2 was found to protect cells against viral infections. here we demonstrate that the individual loss of either 4e-bp1 or 4e-bp2 in mouse embryonic fibroblasts (mefs) is sufficient to confer viral resistance. shrna-mediated silencing of 4e-bp1 or 4e-bp2 renders mefs resistant to viruses, and compared to wild type cells, mefs knockout for either 4e-bp1 or 4e-bp2 exhibit enhanced translation of irf-7 and consequently increased innate immune response to viruse ... | 2014 | 25531441 |
| enhancing and initiating phage-based therapies. | drug development has typically been a primary foundation of strategy for systematic, long-range management of pathogenic cells. however, drug development is limited in speed and flexibility when response is needed to changes in pathogenic cells, especially changes that produce drug-resistance. the high replication speed and high diversity of phages are potentially useful for increasing both response speed and response flexibility when changes occur in either drug resistance or other aspects of p ... | 2014 | 26713220 |
| capacity of mosquitoes to transmit malaria depends on larval environment. | adult traits of holometabolous insects such as reproduction and survival can be shaped by conditions experienced during larval development. these "carry-over" effects influence not only individual life history and fitness, but can also impact interactions between insect hosts and parasites. despite this, the implications of larval conditions for the transmission of human, wildlife and plant diseases that are vectored by insects remain poorly understood. | 2014 | 25496502 |
| oxidative stress influences positive strand rna virus genome synthesis and capping. | flaviviruses are 5' capped positive-stranded rna viruses that replicate their genomes within endoplasmic reticulum-derived vesicles. flaviviruses are well known to induce oxidative stress late in infection but it is unknown if oxidative stress plays a positive role in the viral rna replication cycle. we therefore examined how oxidation affects flavivirus rna replication. we found that antioxidant treatment reduced virus production, reduced the viral positive-to-negative strand rna ratio, and res ... | 2014 | 25514423 |
| ddx17: structured rna recognition drives diverse outputs. | | 0 | 25493410 |
| synaptic strength is bidirectionally controlled by opposing activity-dependent regulation of nedd4-1 and usp8. | the trafficking of ampa receptors (ampars) to and from synapses is crucial for synaptic plasticity. previous work has demonstrated that ampars undergo activity-dependent ubiquitination by the e3 ubiquitin ligase nedd4-1, which promotes their internalization and degradation in lysosomes. here, we define the molecular mechanisms involved in ubiquitination and deubiquitination of ampars. we report that nedd4-1 is rapidly redistributed to dendritic spines in response to ampar activation and not in r ... | 0 | 25505317 |
| the toll-dorsal pathway is required for resistance to viral oral infection in drosophila. | pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. here we investigate the role of the toll pathway in resistance to oral viral infection in d. melanogaster. we show that several toll pathway components, including spätzle, toll, pelle and the nf-kb-like transcription factor dorsal, are required to resist oral ... | 2014 | 25473839 |
| mosquitoes (diptera: culicidae) and their relevance as disease vectors in the city of vienna, austria. | mosquitoes (diptera: culicidae) are important vectors for a wide range of pathogenic organisms. as large parts of the human population in developed countries live in cities, the occurrence of vector-borne diseases in urban areas is of particular interest for epidemiologists and public health authorities. in this study, we investigated the mosquito occurrence in the city of vienna, austria, in order to estimate the risk of transmission of mosquito-borne diseases. mosquitoes were captured using di ... | 2014 | 25468380 |
| drosophila c virus systemic infection leads to intestinal obstruction. | drosophila c virus (dcv) is a positive-sense rna virus belonging to the dicistroviridae family. this natural pathogen of the model organism drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both rna interference and inducible responses. although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. here, we characterize the ... | 2014 | 25253354 |
| vaccines against respiratory viral pathogens for use in neonates: opportunities and challenges. | the first six months of life reflect a time of high susceptibility to severe disease following respiratory virus infection. although this could be improved significantly by immunization, current vaccines are not approved for use in these very young individuals. this is the result of the combined effects of poor immune responsiveness and safety concerns regarding the use of live attenuated vaccines or potent adjuvants in this population. vaccines to effectively combat respiratory viral infection ... | 0 | 25411431 |
| virus-host interactomics: new insights and opportunities for antiviral drug discovery. | the current therapeutic arsenal against viral infections remains limited, with often poor efficacy and incomplete coverage, and appears inadequate to face the emergence of drug resistance. our understanding of viral biology and pathophysiology and our ability to develop a more effective antiviral arsenal would greatly benefit from a more comprehensive picture of the events that lead to viral replication and associated symptoms. towards this goal, the construction of virus-host interactomes is in ... | 2014 | 25593595 |
| interferon-stimulated gene 15 (isg15) and isg15-linked proteins can associate with members of the selective autophagic process, histone deacetylase 6 (hdac6) and sqstm1/p62. | the ubiquitin-like interferon (ifn)-stimulated gene 15 (isg15) and its specific e1, e2, and e3 enzymes are transcriptionally induced by type i ifns. isg15 conjugates newly synthesized proteins. isg15 linkage to proteins appears to be an important downstream ifn signaling event that discriminates cellular and pathogenic proteins synthesized during ifn stimulation from existing proteins. this eliminates potentially pathogenic proteins as the cell attempts to return to normal homeostasis after ifn ... | 2014 | 25429107 |
| interferon-induced ifit proteins: their role in viral pathogenesis. | a major component of the protective antiviral host defense is contributed by the intracellular actions of the proteins encoded by interferon-stimulated genes (isgs); among these are the interferon-induced proteins with tetratricopeptide repeats (ifits), consisting of four members in human and three in mouse. ifit proteins do not have any known enzyme activity. instead, they inhibit virus replication by binding and regulating the functions of cellular and viral proteins and rnas. although all ifi ... | 2014 | 25428874 |
| the nsp3 macrodomain promotes virulence in mice with coronavirus-induced encephalitis. | all coronaviruses encode a macrodomain containing adp-ribose-1"-phosphatase (adrp) activity within the n terminus of nonstructural protein 3 (nsp3). previous work showed that mouse hepatitis virus strain a59 (mhv-a59) with a mutated catalytic site (n1348a) replicated similarly to wild-type virus but was unable to cause acute hepatitis in mice. to determine whether this attenuated phenotype is applicable to multiple disease models, we mutated the catalytic residue in the jhm strain of mhv (jhmv), ... | 2014 | 25428866 |
| going viral and the fatal vulnerability of neurons from immunity, not from infection. | | 2014 | 25422437 |
| detection of chikungunya virus antigen by a novel rapid immunochromatographic test. | chikungunya fever is a mosquito-borne disease of key public health importance in tropical and subtropical countries. although severe joint pain is the most distinguishing feature of chikungunya fever, diagnosis remains difficult because the symptoms of chikungunya fever are shared by many pathogens, including dengue fever. the present study aimed to develop a new immunochromatographic diagnosis test for the detection of chikungunya virus antigen in serum. mice were immunized with isolates from p ... | 2014 | 25411170 |
| mosquito immunity against arboviruses. | arthropod-borne viruses (arboviruses) pose a significant threat to global health, causing human disease with increasing geographic range and severity. the recent availability of the genome sequences of medically important mosquito species has kick-started investigations into the molecular basis of how mosquito vectors control arbovirus infection. here, we discuss recent findings concerning the role of the mosquito immune system in antiviral defense, interactions between arboviruses and fundament ... | 2014 | 25415198 |
| emerging biomedical applications of nano-chitins and nano-chitosans obtained via advanced eco-friendly technologies from marine resources. | the present review article is intended to direct attention to the technological advances made in the 2010-2014 quinquennium for the isolation and manufacture of nanofibrillar chitin and chitosan. otherwise called nanocrystals or whiskers, n-chitin and n-chitosan are obtained either by mechanical chitin disassembly and fibrillation optionally assisted by sonication, or by e-spinning of solutions of polysaccharides often accompanied by poly(ethylene oxide) or poly(caprolactone). the biomedical are ... | 2014 | 25415349 |
| enterovirus 71 induces mitochondrial reactive oxygen species generation that is required for efficient replication. | redox homeostasis is an important host factor determining the outcome of infectious disease. enterovirus 71 (ev71) infection has become an important endemic disease in southeast asia and china. we have previously shown that oxidative stress promotes viral replication, and progeny virus induces oxidative stress in host cells. the detailed mechanism for reactive oxygen species (ros) generation in infected cells remains elusive. in the current study, we demonstrate that mitochondria were a major ro ... | 2014 | 25401329 |
| immune responses to non-tumor antigens in the central nervous system. | the central nervous system (cns), once viewed as an immune-privileged site protected by the blood-brain barrier (bbb), is now known to be a dynamic immunological environment through which immune cells migrate to prevent and respond to events such as localized infection. during these responses, endogenous glial cells, including astrocytes and microglia, become highly reactive and may secrete inflammatory mediators that regulate bbb permeability and recruit additional circulating immune cells. her ... | 2014 | 25431758 |
| a drosophila toolkit for the visualization and quantification of viral replication launched from transgenic genomes. | arthropod rna viruses pose a serious threat to human health, yet many aspects of their replication cycle remain incompletely understood. here we describe a versatile drosophila toolkit of transgenic, self-replicating genomes ('replicons') from sindbis virus that allow rapid visualization and quantification of viral replication in vivo. we generated replicons expressing luciferase for the quantification of viral replication, serving as useful new tools for large-scale genetic screens for identify ... | 2014 | 25386852 |
| mechanism and treatment for learning and memory deficits in mouse models of noonan syndrome. | in noonan syndrome (ns) 30-50% of subjects show cognitive deficits of unknown etiology and with no known treatment. here, we report that knock-in mice expressing either of two ns-associated mutations in ptpn11, which encodes the nonreceptor protein tyrosine phosphatase shp2, show hippocampal-dependent impairments in spatial learning and deficits in hippocampal long-term potentiation (ltp). in addition, viral overexpression of an ns-associated allele ptpn11(d61g) in adult mouse hippocampus result ... | 2014 | 25383899 |
| macroautophagy proteins assist epstein barr virus production and get incorporated into the virus particles. | epstein barr virus (ebv) persists as a latent herpes virus infection in the majority of the adult human population. the virus can reactivate from this latent infection into lytic replication for virus particle production. here, we report that autophagic membranes, which engulf cytoplasmic constituents during macroautophagy and transport them to lysosomal degradation, are stabilized by lytic ebv replication in infected epithelial and b cells. inhibition of autophagic membrane formation compromise ... | 2014 | 26137519 |
| organ-specific protective role of nkt cells in virus-induced inflammatory demyelination and myocarditis depends on mouse strain. | theiler's murine encephalomyelitis virus (tmev) can induce demyelination or myocarditis in susceptible mouse strains. a deficiency of nkt cells exacerbated tmev-induced demyelinating disease (tmev-idd) in sjl/j and balb/c mice. in c57bl/6 background, however, nkt-cell-deficient jα18 ko mice remained as resistant to tmev-idd as wild-type mice. echocardiography and histology showed that jα18 ko mice developed more severe myocarditis (greater t cell infiltration and fibrosis) than wild-type mice, s ... | 2014 | 25434008 |
| response to voinnet et al. | | 0 | 25437535 |
| targeting axonal protein synthesis in neuroregeneration and degeneration. | localized protein synthesis is a mechanism by which morphologically polarized cells react in a spatially confined and temporally acute manner to changes in their environment. during the development of the nervous system intra-axonal protein synthesis is crucial for the establishment of neuronal connections. in contrast, mature axons have long been considered as translationally inactive but upon nerve injury or under neurodegenerative conditions specific subsets of mrnas are recruited into axons ... | 0 | 25371166 |
| cytoplasmic rna granules and viral infection. | rna granules are dynamic cellular structures essential for proper gene expression and homeostasis. the two principal types of cytoplasmic rna granules are stress granules, which contain stalled translation initiation complexes, and processing bodies (p bodies), which concentrate factors involved in mrna degradation. rna granules are associated with gene silencing of transcripts; thus, viruses repress rna granule functions to favor replication. this article discusses the breadth of viral interact ... | 0 | 26958719 |
| mining the human autoantibody repertoire: isolation of potent il17a-neutralizing monoclonal antibodies from a patient with thymoma. | anti-cytokine autoantibodies have been widely reported to be present in human plasma, both in healthy subjects and in patients with underlying autoimmune conditions, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (apeced) or thymic epithelial neoplasms. while often asymptomatic, they can cause or facilitate a wide range of diseases including opportunistic infections. the potential therapeutic value of specific neutralizing anti-cytokine autoantibodies has not been thoroug ... | 0 | 25484038 |
| ifitm-family proteins: the cell's first line of antiviral defense. | animal cells use a wide variety of mechanisms to slow or prevent replication of viruses. these mechanisms are usually mediated by antiviral proteins whose expression and activities can be constitutive but are frequently amplified by interferon induction. among these interferon-stimulated proteins, members of the ifitm (interferon-induced transmembrane) family are unique because they prevent infection before a virus can traverse the lipid bilayer of the cell. at least three human ifitm proteins-i ... | 0 | 25599080 |
| viruses and rna interference: issues and controversies. | the question of whether any mammalian cells are able to mount an effective rna interference-mediated antiviral innate immune response has remained highly controversial. in this gem, i review recent data addressing this important issue and propose a testable hypothesis that can explain many of the apparently contradictory results published in this area of research. | 2014 | 25210170 |
| interleukin 10 modulation of pathogenic th17 cells during fatal alphavirus encephalomyelitis. | mosquito-borne alphaviruses are important causes of epidemic encephalomyelitis. neuronal cell death during fatal alphavirus encephalomyelitis is immune-mediated; however, the types of cells involved and their regulation have not been determined. we show that the virus-induced inflammatory response was accompanied by production of the regulatory cytokine il-10, and in the absence of il-10, paralytic disease occurred earlier and mice died faster. to determine the reason for accelerated disease in ... | 2014 | 25362048 |
| a cytoplasmic rna virus generates functional viral small rnas and regulates viral ires activity in mammalian cells. | the roles of virus-derived small rnas (vsrnas) have been studied in plants and insects. however, the generation and function of small rnas from cytoplasmic rna viruses in mammalian cells remain unexplored. this study describes four vsrnas that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. viral infection produced substantial levels (>10(5) copy numbers per cell) of vsrna1, one of the four vsrnas. we also demonstrated that dicer is involved in ... | 2014 | 25352551 |
| ribosomal readthrough at a short uga stop codon context triggers dual localization of metabolic enzymes in fungi and animals. | translation of mrna into a polypeptide chain is a highly accurate process. many prokaryotic and eukaryotic viruses, however, use leaky termination of translation to optimize their coding capacity. although growing evidence indicates the occurrence of ribosomal readthrough also in higher organisms, a biological function for the resulting extended proteins has been elucidated only in very few cases. here, we report that in human cells programmed stop codon readthrough is used to generate peroxisom ... | 2014 | 25340584 |
| autophagy restricts hiv-1 infection by selectively degrading tat in cd4+ t lymphocytes. | autophagy is a ubiquitous mechanism involved in the lysosomal-mediated degradation of cellular components when they are engulfed in vacuoles called autophagosomes. autophagy is also recognized as an important regulator of the innate and adaptive immune responses against numerous pathogens, which have, therefore, developed strategies to block or use the autophagy machinery to their own benefit. upon human immunodeficiency virus type 1 (hiv-1) infection, viral envelope (env) glycoproteins induce a ... | 2014 | 25339774 |
| the ubiquitin c-terminal hydrolase l1 (uch-l1) c terminus plays a key role in protein stability, but its farnesylation is not required for membrane association in primary neurons. | ubiquitin c-terminal hydrolase l1 (uch-l1) is a deubiquitinating enzyme that is highly expressed in neurons. a possible role for uch-l1 in neurodegeneration has been highlighted because of its presence in lewy bodies associated with parkinson disease and neurofibrillary tangles observed in alzheimer disease. uch-l1 exists in two forms in neurons, a soluble cytoplasmic form (uch-l1(c)) and a membrane-associated form (uch-l1(m)). alzheimer brains show reduced levels of soluble uch-l1(c) correlatin ... | 2014 | 25326379 |
| venezuelan equine encephalitis virus variants lacking transcription inhibitory functions demonstrate highly attenuated phenotype. | alphaviruses represent a significant public health threat worldwide. they are transmitted by mosquitoes and cause a variety of human diseases ranging from severe meningoencephalitis to polyarthritis. to date, no efficient and safe vaccines have been developed against any alphavirus infection. however, in recent years, significant progress has been made in understanding the mechanism of alphavirus replication and virus-host interactions. these data have provided the possibility for the developmen ... | 2014 | 25320296 |
| differentiation of neurons restricts arbovirus replication and increases expression of the alpha isoform of irf-7. | susceptibility to alphavirus infection is age dependent, and host maturation is associated with decreased virus replication and less severe encephalitis. to identify factors associated with maturation-dependent restriction of virus replication, we studied ap-7 rat olfactory bulb neuronal cells, which can differentiate in vitro. differentiation was associated with a 150- to 1,000-fold decrease in replication of the alphaviruses sindbis virus and venezuelan equine encephalitis virus, as well as la ... | 2014 | 25320290 |
| variations in ph sensitivity, acid stability, and fusogenicity of three influenza virus h3 subtypes. | influenza a virus strains adapt to achieve successful entry into host species. entry is mediated by the viral membrane protein hemagglutinin (ha), which triggers membrane fusion and genome release under acidic conditions in the endosome. in addition to changes in the receptor binding domain, the acid stability of ha has been linked to the successful transmission of virus between avian and human hosts. however, to fully understand the connection between changes in ha and host tropism, additional ... | 2014 | 25320308 |
| novel mode of isg15-mediated protection against influenza a virus and sendai virus in mice. | isg15 is a diubiquitin-like modifier and one of the most rapidly induced genes upon type i interferon stimulation. hundreds of host proteins and a number of viral proteins have been shown to be isgylated, and understanding how these modifications affect the interferon response and virus replication has been of considerable interest. isg15(-/-) mice exhibit increased susceptibility to viral infection, and in the case of influenza b virus and vaccinia virus, isg15 conjugation has been shown to res ... | 2014 | 25320315 |
| alginate hydrogel protects encapsulated hepatic huh-7 cells against hepatitis c virus and other viral infections. | cell microencapsulation in alginate hydrogel has shown interesting applications in regenerative medicine and the biomedical field through implantation of encapsulated tissue or for bioartificial organ development. although alginate solution is known to have low antiviral activity, the same property regarding alginate gel has not yet been studied. the aim of this work is to investigate the potential protective effect of alginate encapsulation against hepatitis c virus (hcv) infection for a hepati ... | 2014 | 25310111 |
| age-dependent myeloid dendritic cell responses mediate resistance to la crosse virus-induced neurological disease. | la crosse virus (lacv) is the major cause of pediatric viral encephalitis in the united states; however, the mechanisms responsible for age-related susceptibility in the pediatric population are not well understood. our current studies in a mouse model of lacv infection indicated that differences in myeloid dendritic cell (mdc) responses between weanling and adult mice accounted for susceptibility to lacv-induced neurological disease. we found that type i interferon (ifn) responses were signific ... | 2014 | 25008929 |
| short self-interacting n-terminal region of rubella virus capsid protein is essential for cooperative actions of capsid and nonstructural p150 proteins. | nucleocapsid formation is a primary function of the rubella virus capsid protein, which also promotes viral rna synthesis via an unknown mechanism. the present study demonstrates that in infected cells, the capsid protein is associated with the nonstructural p150 protein via the short self-interacting n-terminal region of the capsid protein. mutational analyses indicated that hydrophobic amino acids in this n-terminal region are essential for its n-terminal self-interaction, which is critical fo ... | 2014 | 25056903 |
| regulation of autophagic activation by rta of epstein-barr virus via the extracellular signal-regulated kinase pathway. | autophagy is an intracellular degradation pathway that provides a host defense mechanism against intracellular pathogens. however, many viruses exploit this mechanism to promote their replication. this study shows that lytic induction of epstein-barr virus (ebv) increases the membrane-bound form of lc3 (lc3-ii) and lc3-containing punctate structures in ebv-positive cells. transfecting 293t cells with a plasmid that expresses rta also induces autophagy, revealing that rta is responsible for autop ... | 2014 | 25122800 |
| a chimeric virus-mouse model system for evaluating the function and inhibition of papain-like proteases of emerging coronaviruses. | to combat emerging coronaviruses, developing safe and efficient platforms to evaluate viral protease activities and the efficacy of protease inhibitors is a high priority. here, we exploit a biosafety level 2 (bsl-2) chimeric sindbis virus system to evaluate protease activities and the efficacy of inhibitors directed against the papain-like protease (plpro) of severe acute respiratory syndrome coronavirus (sars-cov), a biosafety level 3 (bsl-3) pathogen. we engineered sindbis virus to coexpress ... | 2014 | 25100850 |
| engineering recombinant orsay virus directly in the metazoan host caenorhabditis elegans. | the recent identification of orsay virus, the first virus that is capable of naturally infecting caenorhabditis elegans, provides a unique opportunity to explore host-virus interaction studies in this invaluable model organism. a key feature of this system is the robust genetic tractability of the host, c. elegans, which would ideally be complemented by the ability to genetically manipulate orsay virus in parallel. to this end, we developed a plasmid-based reverse genetics system for orsay virus ... | 2014 | 25078701 |
| phosphatidylserine receptors: enhancers of enveloped virus entry and infection. | a variety of both rna and dna viruses envelop their capsids in a lipid bilayer. one of the more recently appreciated benefits this envelope is incorporation of phosphatidylserine (ptdser). surface exposure of ptdser disguises viruses as apoptotic bodies; tricking cells into engulfing virions. this mechanism is termed apoptotic mimicry. several ptdser receptors have been identified to enhance virus entry and we have termed this group of proteins ptdser-mediated virus entry enhancing receptors or ... | 2014 | 25277499 |
| potent immune responses in rhesus macaques induced by nonviral delivery of a self-amplifying rna vaccine expressing hiv type 1 envelope with a cationic nanoemulsion. | self-amplifying messenger rna (mrna) of positive-strand rna viruses are effective vectors for in situ expression of vaccine antigens and have potential as a new vaccine technology platform well suited for global health applications. the sam vaccine platform is based on a synthetic, self-amplifying mrna delivered by a nonviral delivery system. the safety and immunogenicity of an hiv sam vaccine encoding a clade c envelope glycoprotein formulated with a cationic nanoemulsion (cne) delivery system ... | 2014 | 25234719 |
| sponging of cellular proteins by viral rnas. | viral rnas accumulate to high levels during infection and interact with a variety of cellular factors including mirnas and rna-binding proteins. although many of these interactions exist to directly modulate replication, translation and decay of viral transcripts, evidence is emerging that abundant viral rnas may in certain cases serve as a sponge to sequester host non-coding rnas and proteins. by effectively reducing the ability of cellular rna binding proteins to regulate host cell gene expres ... | 2014 | 25233339 |
| virus-mediated compartmentalization of the host translational machinery. | viruses require the host translational apparatus to synthesize viral proteins. host stress response mechanisms that suppress translation, therefore, represent a significant obstacle that viruses must overcome. here, we report a strategy whereby the mammalian orthoreoviruses compartmentalize the translational machinery within virus-induced inclusions known as viral factories (vf). vf are the sites of reovirus replication and assembly but were thought not to contain ribosomes. it was assumed viral ... | 2014 | 25227463 |
| differential release of β-amyloid from dendrite- versus axon-targeted app. | the β-amyloid precursor protein (app) plays a central role in the pathogenesis of alzheimer's disease. app is processed in neurons, but little is known about the relative contributions of presynaptic or postsynaptic compartments to the release of aβ peptides. to address this issue, we transduced primary neurons from sprague-dawley rats or app(-/-) mice (b6.129s7-app(tm1dbo)/j) with lentiviral constructs expressing app chimeras harboring targeting motifs from low-density lipoprotein receptor or n ... | 0 | 25209273 |
| il-1r1 signaling regulates cxcl12-mediated t cell localization and fate within the central nervous system during west nile virus encephalitis. | immune cell entry into the virally infected cns is vital for promoting viral clearance yet may contribute to neuropathology if not rigorously regulated. we previously showed that signaling through il-1r1 is critical for effector t cell reactivation and virologic control within the cns during murine west nile virus (wnv) encephalitis. wnv-infected il-1r1(-/-) mice also display increased parenchymal penetration of cd8(+) t cells despite lack of cd4-mediated full activation, suggesting dysregulatio ... | 2014 | 25200953 |
| intracellular sensing of complement c3 activates cell autonomous immunity. | pathogens traverse multiple barriers during infection, including cell membranes. we found that during this transition, pathogens carried covalently attached complement c3 into the cell, triggering immediate signaling and effector responses. sensing of c3 in the cytosol activated mitochondrial antiviral signaling (mavs)-dependent signaling cascades and induced proinflammatory cytokine secretion. c3 also flagged viruses for rapid proteasomal degradation, preventing their replication. this system c ... | 2014 | 25190799 |
| viral rnas are unusually compact. | a majority of viruses are composed of long single-stranded genomic rna molecules encapsulated by protein shells with diameters of just a few tens of nanometers. we examine the extent to which these viral rnas have evolved to be physically compact molecules to facilitate encapsulation. measurements of equal-length viral, non-viral, coding and non-coding rnas show viral rnas to have among the smallest sizes in solution, i.e., the highest gel-electrophoretic mobilities and the smallest hydrodynamic ... | 2014 | 25188030 |
| current strategic thinking for the development of a trivalent alphavirus vaccine for human use. | vaccinations against the encephalitic alphaviruses (western, eastern, and venezuelan equine encephalitis virus) are of significant interest to biological defense, public health, and agricultural communities alike. although vaccines licensed for veterinary applications are used in the western hemisphere and attenuated or inactivated viruses have been used under investigational new drug status to protect at-risk personnel, there are currently no licensed vaccines for use in humans. here, we will d ... | 2014 | 24842880 |
| nup98 promotes antiviral gene expression to restrict rna viral infection in drosophila. | in response to infection, the innate immune system rapidly activates an elaborate and tightly orchestrated gene expression program to induce critical antimicrobial genes. while many key players in this program have been identified in disparate biological systems, it is clear that there are additional uncharacterized mechanisms at play. our previous studies revealed that a rapidly-induced antiviral gene expression program is active against disparate human arthropod-borne viruses in drosophila. mo ... | 2014 | 25197089 |
| inhibition of west nile virus by calbindin-d28k. | evidence indicates that west nile virus (wnv) employs ca(2+) influx for its replication. moreover, calcium buffer proteins, such as calbindin d28k (cb-d28k), may play an important role mitigating cellular destruction due to disease processes, and more specifically, in some neurological diseases. we addressed the hypothesis that cb-d28k inhibits wnv replication in cell culture and infected rodents. wnv envelope immunoreactivity (ir) was not readily co-localized with cb-d28k ir in wnv-infected ver ... | 2014 | 25180779 |
| host factors that interact with the pestivirus n-terminal protease, npro, are components of the ribonucleoprotein complex. | the viral n-terminal protease n(pro) of pestiviruses counteracts cellular antiviral defenses through inhibition of irf3. here we used mass spectrometry to identify a new role for n(pro) through its interaction with over 55 associated proteins, mainly ribosomal proteins and ribonucleoproteins, including rna helicase a (dhx9), y-box binding protein (ybx1), ddx3, ddx5, eif3, igf2bp1, multiple myeloma tumor protein 2, interleukin enhancer binding factor 3 (iebp3), guanine nucleotide binding protein ... | 2014 | 24965446 |
| hepatitis c virus and cellular stress response: implications to molecular pathogenesis of liver diseases. | infection with hepatitis c virus (hcv) is a leading risk factor for chronic liver disease progression, including steatosis, cirrhosis, and hepatocellular carcinoma. with approximately 3% of the human population infected worldwide, hcv infection remains a global public health challenge. the efficacy of current therapy is still limited in many patients infected with hcv, thus a greater understanding of pathogenesis in hcv infection is desperately needed. emerging lines of evidence indicate that hc ... | 2012 | 23202463 |
| transcriptional pausing controls a rapid antiviral innate immune response in drosophila. | innate immune responses are characterized by precise gene expression whereby gene subsets are temporally induced to limit infection, although the mechanisms involved are incompletely understood. we show that antiviral immunity in drosophila requires the transcriptional pausing pathway, including negative elongation factor (nelf) that pauses rna polymerase ii (pol ii) and positive elongation factor b (p-tefb), which releases paused pol ii to produce full-length transcripts. we identify a set of g ... | 0 | 23084920 |
| dynamic regulation of synaptic maturation state by voltage-gated a-type k+ channels in ca1 hippocampal pyramidal neurons. | neuronal activity is critical for the formation and modification of neural circuits during brain development. in hippocampal ca1 pyramidal dendrites, a-type voltage-gated k(+) currents, formed primarily by kv4.2 subunits, control excitability. here we used kv4.2 knock-out (kv4.2-ko) mice along with acute in vivo expression of kv4.2 or its dominant-negative pore mutant to examine the role of kv4.2 in the development of ca1 synapses. we found that kv4.2 expression induces synaptic maturation in ju ... | 0 | 23055512 |
| gene therapy for gastric cancer: a review. | gastric cancer is common in china, and its early diagnosis and treatment are difficult. in recent years great progress has been achieved in gene therapy, and a wide array of gene therapy systems for gastric cancer has been investigated. the present article deals with the general principles of gene therapy and then focuses on how these principles may be applied to gastric cancer. | 0 | 14606062 |
| real-time imaging of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (ampa receptor) movements in neurons. | the mechanisms that regulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (ampar) synthesis, transport, targeting and surface expression are of fundamental importance for fast excitatory neurotransmission and synaptic plasticity in the mammalian central nervous system. it has become apparent that these control processes involve complex sets of protein-protein interactions and many of the proteins responsible have been identified. we have been working to visualize ampar movem ... | 0 | 12887326 |
| p250gap, a novel brain-enriched gtpase-activating protein for rho family gtpases, is involved in the n-methyl-d-aspartate receptor signaling. | n-methyl-d-aspartate (nmda) receptors regulate structural plasticity by modulating actin organization within dendritic spines. herein, we report identification and characterization of p250gap, a novel gtpase-activating protein for rho family proteins that interacts with the glurepsilon2 (nr2b) subunit of nmda receptors in vivo. the p250gap mrna was enriched in brain, with high expression in cortex, corpus striatum, hippocampus, and thalamus. within neurons, p250gap was highly concentrated in the ... | 2003 | 12857875 |
| nucleic acid-based immune system: the antiviral potential of mammalian rna silencing. | | 0 | 12805414 |
| dna vaccines and apoptosis: to kill or not to kill? | | 0 | 12840054 |
| arboviral bottlenecks and challenges to maintaining diversity and fitness during mosquito transmission. | the term arbovirus denotes viruses that are transmitted by arthropods, such as ticks, mosquitoes, and other biting arthropods. the infection of these vectors produces a certain set of evolutionary pressures on the virus; involving migration from the midgut, where the blood meal containing the virus is processed, to the salivary glands, in order to transmit the virus to the next host. during this process the virus is subject to numerous bottlenecks, stochastic events that significantly reduce the ... | 2014 | 25341663 |
| putative novel lineage of west nile virus in uranotaenia unguiculata mosquito, hungary. | west nile virus (wnv) is an increasing public health concern in europe with numerous human cases. a total of 23,029 female mosquitoes were tested for a variety of mosquito-borne flaviviruses and orthobunyaviruses supposedly endemic in southern transdanubia, hungary, in the frames of a large-scale surveillance between 2011 and 2013. wnv nucleic acid was detected in a single pool containing uranotaenia unguiculata mosquitoes. sequence- and phylogenetic analyses for two different regions (ns5 and e ... | 2014 | 25674630 |
| cellular responses to sindbis virus infection of neural progenitors derived from human embryonic stem cells. | sindbis virus (sinv) causes age-dependent encephalitis in mice, and therefore serves as a model to study viral encephalitis. sinv is used as a vector for the delivery of genes into selected neural stem cell lines; however, the toxicity and side effects of this vector have rarely been discussed. in this context, we investigated the cellular responses of human embryonic stem cell (hescs) derived neural progenitors (hnpcs) to sinv infection by assessing susceptibility of the cells to sinv infection ... | 2014 | 25343994 |
| developing baculovirus-insect cell expression systems for humanized recombinant glycoprotein production. | the baculovirus-insect cell expression system is widely used to produce recombinant glycoproteins for many different biomedical applications. however, due to the fundamental nature of insect glycoprotein processing pathways, this system is typically unable to produce recombinant mammalian glycoproteins with authentic oligosaccharide side chains. this minireview summarizes our current understanding of insect protein glycosylation pathways and our recent efforts to address this problem. these effo ... | 0 | 12788624 |
| orientation refinement of virus structures with unknown symmetry. | structural biology, in particular the structure determination of viruses and other large macromolecular complexes leads to data- and compute-intensive problems that require resources well beyond those available on a single system. thus, there is an imperative need to develop parallel algorithms and programs for clusters and computational grids. we present one of the most challenging computational problems posed by the three-dimensional structure determination of viruses, the orientation refineme ... | 0 | 25580470 |
| the 64-kilodalton capsid protein homolog of beet yellows virus is required for assembly of virion tails. | the filamentous virion of the closterovirus beet yellows virus (byv) consists of a long body formed by the major capsid protein (cp) and a short tail composed of the minor capsid protein (cpm) and the virus-encoded hsp70 homolog. by using nano-liquid chromatography-tandem mass spectrometry and biochemical analyses, we show here that the byv 64-kda protein (p64) is the fourth integral component of byv virions. the n-terminal domain of p64 is exposed at the virion surface and is accessible to anti ... | 0 | 12551975 |
| unique inflammatory rna profiles of microglia in creutzfeldt-jakob disease. | previous studies in creutzfeldt-jakob disease (cjd) have shown that myeloid cells in the periphery as well as derivative microglial cells in the brain are infectious. microglia can show an activated phenotype before prion protein (prp) pathology is detectable in brain, and isolated infectious microglia contain very little prp. to find whether a set of inflammatory genes are significantly induced or suppressed with infection, we analyzed rna from isolated microglia with relevant cdna arrays, and ... | 2003 | 12525699 |
| an mrna-specific trnai carrier eif2a plays a pivotal role in cell proliferation under stress conditions: stress-resistant translation of c-src mrna is mediated by eif2a. | c-src, a non-receptor protein tyrosine kinase, activates nf-κb and stat3, which in turn triggers the transcription of anti-apoptosis- and cell cycle-related genes. c-src protein regulates cell proliferation, cell motility and programmed cell death. and the elevated level of activated c-src protein is related with solid tumor generation. translation of c-src mrna is directed by an ires element which mediates persistent translation under stress conditions when translation of most mrnas is inhibite ... | 2016 | 27899592 |
| fusion-related host proteins are actively regulated by na during influenza infection as revealed by quantitative proteomics analysis. | three recombinant influenza a viruses with different neuraminidases (nas) in the background of a/pr/8/34 (pr8), named rpr8-h5n1na, rpr8-h9n2na, and rpr8-h1n1na, derived from h5n1, h9n2, h1n1 (swine) viruses, respectively, were constructed. we performed a quantitative proteomics analysis to investigate differential protein expression in madin-darby canine kidney (mdck) cells infected with recombinant and wild-type influenza viruses to determine whether na replacement would alter host cell gene ex ... | 2014 | 25153908 |
| assembly and maturation of a t = 4 quasi-equivalent virus is guided by electrostatic and mechanical forces. | nudaurelia capensis w virus (nωv) is a eukaryotic rna virus that is well suited for the study of virus maturation. the virus initially assembles at ph 7.6 into a marginally stable 480-å procapsid formed by 240 copies of a single type of protein subunit. during maturation, which occurs during apoptosis at ph 5.0, electrostatic forces guide subunit trajectories into a robust 410-å virion that is buttressed by subunit associated molecular switches. we discuss the competing factors in the virus caps ... | 2014 | 25153346 |
| a cationic nanoemulsion for the delivery of next-generation rna vaccines. | nucleic acid-based vaccines such as viral vectors, plasmid dna, and mrna are being developed as a means to address a number of unmet medical needs that current vaccine technologies have been unable to address. here, we describe a cationic nanoemulsion (cne) delivery system developed to deliver a self-amplifying mrna vaccine. this nonviral delivery system is based on novartis's proprietary adjuvant mf59, which has an established clinical safety profile and is well tolerated in children, adults, a ... | 2014 | 25027661 |
| computational identification of dengue virus microrna-like structures and their cellular targets. | micrornas (mirnas) are small, noncoding rna molecules that regulate transcriptional and posttranscriptional gene regulation of the cell. experimental evidence shows that mirnas have a direct role in different cellular processes, such as immune function, apoptosis, and tumorigenesis. in a viral infection context, mirnas have been connected with the interplay between host and pathogen, occupying a major role in pathogenesis. while numerous viral mirnas from dna viruses have been identified, charac ... | 2014 | 25210446 |
| stem-loop recognition by ddx17 facilitates mirna processing and antiviral defense. | dead-box helicases play essential roles in rna metabolism across species, but emerging data suggest that they have additional functions in immunity. through rnai screening, we identify an evolutionarily conserved and interferon-independent role for the dead-box helicase ddx17 in restricting rift valley fever virus (rvfv), a mosquito-transmitted virus in the bunyavirus family that causes severe morbidity and mortality in humans and livestock. loss of drosophila ddx17 (rm62) in cells and flies enh ... | 0 | 25126784 |
| development of a reverse genetics system for respiratory syncytial virus long strain and an immunogenicity study of the recombinant virus. | respiratory syncytial virus (rsv) is an important human respiratory pathogen, particularly of infants and older adults, and despite several decades of research and development, no licensed vaccine is available. studies have confirmed that enhancement of rsv disease does not occur after inoculation with rsv live-attenuated vaccine candidates, making such vaccines preferable. in this paper, reverse genetics was used to construct two recombinant viruses, a recombinant long strain (rlong) and rlong- ... | 2014 | 25107552 |
| suppressing dengue-2 infection by chemical inhibition of aedes aegypti host factors. | dengue virus host factors (denv hfs) that are essential for the completion of the infection cycle in the mosquito vector and vertebrate host represent potent targets for transmission blocking. here we investigated whether known mammalian denv hf inhibitors could influence virus infection in the arthropod vector a. aegypti. we evaluated the potency of bafilomycin (baf; inhibitor of vacuolar h+-atpase (vatpase)), mycophenolic acid (mpa; inhibitor of inosine-5'-monophosphate dehydrogenase (impdh)), ... | 2014 | 25101828 |
| development of an algorithm for production of inactivated arbovirus antigens in cell culture. | arboviruses are medically important pathogens that cause human disease ranging from a mild fever to encephalitis. laboratory diagnosis is essential to differentiate arbovirus infections from other pathogens with similar clinical manifestations. the arboviral diseases branch (adb) reference laboratory at the cdc division of vector-borne diseases (dvbd) produces reference antigens used in serological assays such as the virus-specific immunoglobulin m antibody-capture enzyme-linked immunosorbent as ... | 2014 | 25102428 |
| isg15 functions as an interferon-mediated antiviral effector early in the murine norovirus life cycle. | human noroviruses (hunov) are the leading cause of nonbacterial gastroenteritis worldwide. similar to hunov, murine noroviruses (mnv) are enteric pathogens spread via the fecal-oral route and have been isolated from numerous mouse facilities worldwide. type i and type ii interferons (ifn) restrict mnv-1 replication; however, the antiviral effectors impacting mnv-1 downstream of ifn signaling are largely unknown. studies using dendritic cells, macrophages, and mice deficient in free and conjugate ... | 2014 | 24899198 |
| western equine encephalitis virus: evolutionary analysis of a declining alphavirus based on complete genome sequences. | western equine encephalitis virus (weev) is an arbovirus from the genus alphavirus, family togaviridae, which circulates in north america between birds and mosquitoes, occasionally causing disease in humans and equids. in recent decades, human infection has decreased dramatically; the last documented human case in north america occurred in 1994, and the virus has not been detected in mosquito pools since 2008. because limited information exists regarding the evolution of weev, we analyzed the ge ... | 2014 | 24899192 |
| defective viral genomes: critical danger signals of viral infections. | viruses efficiently block the host antiviral response in order to replicate and spread before host intervention. the mechanism initiating antiviral immunity during stealth viral replication is unknown, but recent data demonstrate that defective viral genomes generated at peak virus replication are critical for this process in vivo. this article summarizes the supporting evidence and highlights gaps in our understanding of the mechanisms and impact of immunostimulatory defective viral genomes gen ... | 2014 | 24872580 |
| progression from igd+ igm+ to isotype-switched b cells is site specific during coronavirus-induced encephalomyelitis. | various infections in the central nervous system (cns) trigger b cell accumulation; however, the relative dynamics between viral replication and alterations in distinct b cell subsets are largely unknown. using a glia-tropic coronavirus infection, which is initiated in the brain but rapidly spreads to and predominantly persists in the spinal cord, this study characterizes longitudinal changes in b cell subsets at both infected anatomical sites. the phase of t cell-dependent, antibody-independent ... | 2014 | 24872583 |
| nonneutralizing functional antibodies: a new "old" paradigm for hiv vaccines. | animal and human data from various viral infections and vaccine studies suggest that nonneutralizing antibodies (nnab) without neutralizing activity in vitro may play an important role in protection against viral infection in vivo. this was illustrated by the recent human immunodeficiency virus (hiv) rv144 vaccine efficacy trial, which demonstrated that hiv-specific igg-mediated nnab directed against the v2 loop of hiv type 1 envelope (env) were inversely correlated with risk for hiv acquisition ... | 2014 | 24920599 |
| immunization of mice with lentiviral vectors targeted to mhc class ii+ cells is due to preferential transduction of dendritic cells in vivo. | gene transfer vectors such as lentiviral vectors offer versatile possibilities to express transgenic antigens for vaccination purposes. however, viral vaccines leading to broad transduction and transgene expression in vivo, are undesirable. therefore, strategies capable of directing gene transfer only to professional antigen-presenting cells would increase the specific activity and safety of genetic vaccines. a lentiviral vector pseudotype specific for murine major histocompatibilty complex clas ... | 2014 | 25058148 |
| population structure and distribution patterns of the sibling mosquito species culex pipiens and culex torrentium (diptera: culicidae) reveal different evolutionary paths. | nowadays a number of endemic mosquito species are known to possess vector abilities for various diseases, as e.g. the sibling species culex pipiens and culex torrentium. due to their morphological similarity, ecology, distribution and vector abilities, knowledge about these species' population structure is essential. culicidae from 25 different sampling sites were collected from march till october 2012. all analyses were performed with aligned cox1 sequences with a total length of 658 bp. popula ... | 2014 | 25048456 |
| novel drosophila viruses encode host-specific suppressors of rnai. | the ongoing conflict between viruses and their hosts can drive the co-evolution between host immune genes and viral suppressors of immunity. it has been suggested that an evolutionary 'arms race' may occur between rapidly evolving components of the antiviral rnai pathway of drosophila and viral genes that antagonize it. we have recently shown that viral protein 1 (vp1) of drosophila melanogaster nora virus (dmelnv) suppresses argonaute-2 (ago2)-mediated target rna cleavage (slicer activity) to a ... | 2014 | 25032815 |
| japanese encephalitis virus replication is negatively regulated by autophagy and occurs on lc3-i- and edem1-containing membranes. | autophagy is a lysosomal degradative pathway that has diverse physiological functions and plays crucial roles in several viral infections. here we examine the role of autophagy in the life cycle of jev, a neurotropic flavivirus. jev infection leads to induction of autophagy in several cell types. jev replication was significantly enhanced in neuronal cells where autophagy was rendered dysfunctional by atg7 depletion, and in atg5-deficient mouse embryonic fibroblasts (mefs), resulting in higher v ... | 2014 | 25046112 |
| the impact of the interferon-lambda family on the innate and adaptive immune response to viral infections. | type-iii interferons (ifn-λ, ifnl) are the most recently described family of ifns. this family of innate cytokines are increasingly being ascribed pivotal roles in host-pathogen interactions. herein, we will review the accumulating evidence detailing the immune biology of ifnl during viral infection, and the implications of this novel information on means to advance the development of therapies and vaccines against existing and emerging pathogens. ifnls exert antiviral effects via induction of i ... | 2014 | 26038748 |
| ebv microrna bart 18-5p targets map3k2 to facilitate persistence in vivo by inhibiting viral replication in b cells. | ebv is an oncogenic human herpesvirus that has the ability to infect and transform b cells latently in vitro. however, the virus also establishes a lifetime, benign, persistent latent infection in resting memory b cells in vivo, where the virus is quiescent (i.e., expresses none of the known latent proteins). the virus encodes ∼40 micro-rnas (mirnas), most of which are transcribed from the bamh1 fragment a rightward transcript (bart) region of the virus. we have shown previously that a subset of ... | 2014 | 25012295 |
| cdk9 inhibitor fit-039 prevents replication of multiple dna viruses. | a wide range of antiviral drugs is currently available; however, drug-resistant viruses have begun to emerge and represent a potential public health risk. here, we explored the use of compounds that inhibit or interfere with the action of essential host factors to prevent virus replication. in particular, we focused on the cyclin-dependent kinase 9 (cdk9) inhibitor, fit-039, which suppressed replication of a broad spectrum of dna viruses through inhibition of mrna transcription. specifically, fi ... | 2014 | 25003190 |
| enhancement of protein expression by alphavirus replicons by designing self-replicating subgenomic rnas. | since the development of infectious cdna clones of viral rna genomes and the means of delivery of the in vitro-synthesized rna into cells, alphaviruses have become an attractive system for expression of heterologous genetic information. alphaviruses replicate exclusively in the cytoplasm, and their genetic material cannot recombine with cellular dna. alphavirus genome-based, self-replicating rnas (replicons) are widely used vectors for expression of heterologous proteins. their current design re ... | 2014 | 25002490 |
| association of climatic factors with infectious diseases in the arctic and subarctic region--a systematic review. | the arctic and subarctic area are likely to be highly affected by climate change, with possible impacts on human health due to effects on food security and infectious diseases. | 2014 | 24990685 |
| differential restriction patterns of mrna decay factor auf1 during picornavirus infections. | during infection by picornaviruses, the cellular environment is modified to favour virus replication. this includes the modification of specific host proteins, including the recently discovered viral proteinase cleavage of mrna decay factor au-rich binding factor 1 (auf1). this cellular rna-binding protein was shown previously to act as a restriction factor during poliovirus, rhinovirus and coxsackievirus infection. during infection by these viruses, auf1 relocalizes to the cytoplasm and is clea ... | 2014 | 24722678 |