| rabies control and treatment: from prophylaxis to strategies with curative potential. | rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. in the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. unlike the conventio ... | 2016 | 27801824 |
| new world and old world alphaviruses have evolved to exploit different components of stress granules, fxr and g3bp proteins, for assembly of viral replication complexes. | the positive-strand rna viruses initiate their amplification in the cell from a single genome delivered by virion. this single rna molecule needs to become involved in replication process before it is recognized and degraded by cellular machinery. in this study, we show that distantly related new world and old world alphaviruses have independently evolved to utilize different cellular stress granule-related proteins for assembly of complexes, which recruit viral genomic rna and facilitate format ... | 2016 | 27509095 |
| pathogenic chikungunya virus evades b cell responses to establish persistence. | chikungunya virus (chikv) and related alphaviruses cause epidemics of acute and chronic musculoskeletal disease. to investigate the mechanisms underlying the failure of immune clearance of chikv, we studied mice infected with an attenuated chikv strain (181/25) and the pathogenic parental strain (af15561), which differ by five amino acids. whereas af15561 infection of wild-type mice results in viral persistence in joint tissues, 181/25 is cleared. in contrast, 181/25 infection of μmt mice lackin ... | 2016 | 27452455 |
| combined structural, biochemical and cellular evidence demonstrates that both fgdf motifs in alphavirus nsp3 are required for efficient replication. | recent findings have highlighted the role of the old world alphavirus non-structural protein 3 (nsp3) as a host defence modulator that functions by disrupting stress granules, subcellular phase-dense rna/protein structures formed upon environmental stress. this disruption mechanism was largely explained through nsp3-mediated recruitment of the host g3bp protein via two tandem fgdf motifs. here, we present the 1.9 å resolution crystal structure of the ntf2-like domain of g3bp-1 in complex with a ... | 0 | 27383630 |
| computational virology: from the inside out. | viruses typically pack their genetic material within a protein capsid. enveloped viruses also have an outer membrane made up of a lipid bilayer and membrane-spanning glycoproteins. x-ray diffraction and cryoelectron microscopy provide high resolution static views of viral structure. molecular dynamics (md) simulations may be used to provide dynamic insights into the structures of viruses and their components. there have been a number of simulations of viral capsids and (in some cases) of the inn ... | 2016 | 26874202 |
| pirna pathway is not required for antiviral defense in drosophila melanogaster. | since its discovery, rna interference has been identified as involved in many different cellular processes, and as a natural antiviral response in plants, nematodes, and insects. in insects, the small interfering rna (sirna) pathway is the major antiviral response. in recent years, the piwi-interacting rna (pirna) pathway also has been implicated in antiviral defense in mosquitoes infected with arboviruses. using drosophila melanogaster and an array of viruses that infect the fruit fly acutely o ... | 2016 | 27357659 |
| who regulates whom? an overview of rna granules and viral infections. | after viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mrna translation (protein synthesis) and the assembly of rna granules. two of these rna granules have been well characterized in yeast and mammalian cells, stress granules (sgs), which are translationally silent sites of rna triage and processing bodies (pbs), which are involved in mrna degradation. this review discusses the ... | 2016 | 27367717 |
| alphavirus restriction by ifitm proteins. | interferon inducible transmembrane proteins (ifitms) are broad-spectrum antiviral factors. in cell culture the entry of many enveloped viruses, including orthomyxo-, flavi-, and filoviruses, is inhibited by ifitms, though the mechanism(s) involved remain unclear and may vary between viruses. we demonstrate that sindbis and semliki forest virus (sfv), which both use endocytosis and acid-induced membrane fusion in early endosomes to infect cells, are restricted by the early endosomal ifitm3. the l ... | 2016 | 27219333 |
| adapting the stress response: viral subversion of the mtor signaling pathway. | the mammalian target of rapamycin (mtor) is a central regulator of gene expression, translation and various metabolic processes. multiple extracellular (growth factors) and intracellular (energy status) molecular signals as well as a variety of stressors are integrated into the mtor pathway. viral infection is a significant stress that can activate, reduce or even suppress the mtor signaling pathway. consequently, viruses have evolved a plethora of different mechanisms to attack and co-opt the m ... | 2016 | 27231932 |
| glial cell activation, recruitment, and survival of b-lineage cells following mcmv brain infection. | chemokines produced by reactive glia drive migration of immune cells and previous studies from our laboratory have demonstrated that cd19(+) b cells infiltrate the brain. in this study, in vivo and in vitro experiments investigated the role of reactive glial cells in recruitment and survival of b-lineage cells in response to (murine cytomegalovirus) mcmv infection. | 2016 | 27207308 |
| making bunyaviruses talk: interrogation tactics to identify host factors required for infection. | the identification of host cellular genes that act as either proviral or antiviral factors has been aided by the development of an increasingly large number of high-throughput screening approaches. here, we review recent advances in which these new technologies have been used to interrogate host genes for the ability to impact bunyavirus infection, both in terms of technical advances as well as a summary of biological insights gained from these studies. | 2016 | 27187446 |
| dengue virus reporter replicon is a valuable tool for antiviral drug discovery and analysis of virus replication mechanisms. | dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (denv), a member of the flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. however, no specific antiviral drug or licensed vaccine currently targets denv infection. the replicon system has all the factors needed for viral replication in cells. since the development of replicon systems, transient and stable reporter replicon ... | 2016 | 27164125 |
| role of tspan9 in alphavirus entry and early endosomes. | alphaviruses are small enveloped rna viruses that infect cells via clathrin-mediated endocytosis and low-ph-triggered fusion in the early endosome. using a small interfering rna (sirna) screen in human cells, we previously identified tspan9 as a host factor that promotes infection by the alphaviruses sindbis virus (sinv), semliki forest virus (sfv), and chikungunya virus (chikv). depletion of tspan9 specifically decreases sfv membrane fusion in endosomes. tspan9 is a member of the tetraspanin fa ... | 2016 | 26865714 |
| sirna screen identifies trafficking host factors that modulate alphavirus infection. | little is known about the repertoire of cellular factors involved in the replication of pathogenic alphaviruses. to uncover molecular regulators of alphavirus infection, and to identify candidate drug targets, we performed a high-content imaging-based sirna screen. we revealed an actin-remodeling pathway involving rac1, pip5k1- α, and arp3, as essential for infection by pathogenic alphaviruses. infection causes cellular actin rearrangements into large bundles of actin filaments termed actin foci ... | 2016 | 27031835 |
| versatile trans-replication systems for chikungunya virus allow functional analysis and tagging of every replicase protein. | chikungunya virus (chikv; genus alphavirus, family togaviridae) has recently caused several major outbreaks affecting millions of people. there are no licensed vaccines or antivirals, and the knowledge of the molecular biology of chikv, crucial for development of efficient antiviral strategies, remains fragmentary. chikv has a 12 kb positive-strand rna genome, which is translated to yield a nonstructural (ns) or replicase polyprotein. chikv structural proteins are expressed from a subgenomic rna ... | 2016 | 26963103 |
| arbovirus-mosquito interactions: rnai pathway. | arthropod-borne (arbo) viruses infect hematophagous arthropods (vectors) to maintain virus transmission between vertebrate hosts. the mosquito vector actively controls arbovirus infection to minimize its fitness costs. the rna interference (rnai) pathway is the major antiviral response vectors use to restrict arbovirus infections. we know this because depleting rnai gene products profoundly impacts arbovirus replication, the antiviral rnai pathway genes undergo positive, diversifying selection a ... | 2015 | 26629932 |
| fluorescent protein-tagged sindbis virus e2 glycoprotein allows single particle analysis of virus budding from live cells. | sindbis virus (sinv) is an enveloped, mosquito-borne alphavirus. here we generated and characterized a fluorescent protein-tagged (fp-tagged) sinv and found that the presence of the fp-tag (mcherry) affected glycoprotein transport to the plasma membrane whereas the specific infectivity of the virus was not affected. we examined the virions by transmission electron cryo-microscopy and determined the arrangement of the fp-tag on the surface of the virion. the fluorescent proteins are arranged icos ... | 2015 | 26633461 |
| battle between influenza a virus and a newly identified antiviral activity of the parp-containing zapl protein. | previous studies showed that zapl (parp-13.1) exerts its antiviral activity via its n-terminal zinc fingers that bind the mrnas of some viruses, leading to mrna degradation. here we identify a different antiviral activity of zapl that is directed against influenza a virus. this zapl antiviral activity involves its c-terminal parp domain, which binds the viral pb2 and pa polymerase proteins, leading to their proteasomal degradation. after the pb2 and pa proteins are poly(adp-ribosylated), they ar ... | 2015 | 26504237 |
| sphingosine kinase 2 is a chikungunya virus host factor co-localized with the viral replication complex. | chikungunya virus (chikv) is a re-emerging alphavirus which causes severe and prolonged arthralgic febrile illness. the recent global spread of the virus and lack of approved therapeutic options makes it imperative to gain greater insight into the molecular mechanisms underlying chikv pathogenesis, in particular host factors recruited by the virus. in the current study, we identify sphingosine kinase 2 (sk2) as a chikv host factor co-localized with the viral replication complex (vrc) during infe ... | 2015 | 26576339 |
| immunoproteomic profiling of antiviral antibodies in new-onset type 1 diabetes using protein arrays. | the rapid rise in the incidence of type 1 diabetes (t1d) suggests the involvement of environmental factors including viral infections. we evaluated the association between viral infections and t1d by profiling antiviral antibodies using a high-throughput immunoproteomics approach in patients with new-onset t1d. we constructed a viral protein array comprising the complete proteomes of seven viruses associated with t1d and open reading frames from other common viruses. antibody responses to 646 vi ... | 2015 | 26450993 |
| interactions involved in ph protection of the alphavirus fusion protein. | the alphavirus membrane protein e1 mediates low ph-triggered fusion of the viral and endosome membranes during virus entry. during virus biogenesis e1 associates as a heterodimer with the transmembrane protein p62. late in the secretory pathway, cellular furin cleaves p62 to the mature e2 protein and a peripheral protein e3. e3 remains bound to e2 at low ph, stabilizing the heterodimer and thus protecting e1 from the acidic ph of the secretory pathway. release of e3 at neutral ph then primes the ... | 2015 | 26433749 |
| mosquito rasputin interacts with chikungunya virus nsp3 and determines the infection rate in aedes albopictus. | chikungunya virus (chikv) is an arthritogenic alphavirus (family togaviridae), transmitted by aedes species mosquitoes. chikv re-emerged in 2004 with multiple outbreaks worldwide and recently reached the americas where it has infected over a million individuals in a rapidly expanding epidemic. while alphavirus replication is well understood in general, the specific function (s) of non-structural protein nsp3 remain elusive. chikv nsp3 modulates the mammalian stress response by preventing stress ... | 2015 | 26384002 |
| japanese encephalitis virus replicon-based vaccine expressing enterovirus-71 epitope confers dual protection from lethal challenges. | to construct safer recombinant flavivirus vaccine, we exploited japanese encephalitis virus (jev) replicon-based platform to generate single-round infectious particles (srips) that expressed heterologous neutralizing epitope sp70 derived from enterovirus-71 (ev71). such pseudo-infectious virus particles, named srip-sp70, although are not genuine viable viruses, closely mimic live virus infection to elicit immune responses within one round of viral life cycle. | 2015 | 26362772 |
| differential phosphatidylinositol-3-kinase-akt-mtor activation by semliki forest and chikungunya viruses is dependent on nsp3 and connected to replication complex internalization. | many viruses affect or exploit the phosphatidylinositol-3-kinase (pi3k)-akt-mammalian target of rapamycin (mtor) pathway, a crucial prosurvival signaling cascade. we report that this pathway was strongly activated in cells upon infection with the old world alphavirus semliki forest virus (sfv), even under conditions of complete nutrient starvation. we mapped this activation to the hyperphosphorylated/acidic domain in the c-terminal tail of sfv nonstructural protein nsp3. viruses with a deletion ... | 2015 | 26339054 |
| alphavirus rna synthesis and non-structural protein functions. | the members of the genus alphavirus are positive-sense rna viruses, which are predominantly transmitted to vertebrates by a mosquito vector. alphavirus disease in humans can be severely debilitating, and depending on the particular viral species, infection may result in encephalitis and possibly death. in recent years, alphaviruses have received significant attention from public health authorities as a consequence of the dramatic emergence of chikungunya virus in the indian ocean islands and the ... | 2015 | 26219641 |
| dna-launched alphavirus replicons encoding a fusion of mycobacterial antigens acr and ag85b are immunogenic and protective in a murine model of tb infection. | there is an urgent need for effective prophylactic measures against mycobacterium tuberculosis (mtb) infection, particularly given the highly variable efficacy of bacille calmette-guerin (bcg), the only licensed vaccine against tuberculosis (tb). most studies indicate that cell-mediated immune responses involving both cd4+ and cd8+ t cells are necessary for effective immunity against mtb. genetic vaccination induces humoral and cellular immune responses, including cd4+ and cd8+ t-cell responses, ... | 2015 | 26317509 |
| differences in processing determinants of nonstructural polyprotein and in the sequence of nonstructural protein 3 affect neurovirulence of semliki forest virus. | the a7(74) strain of semliki forest virus (sfv; genus alphavirus) is avirulent in adult mice, while the l10 strain is virulent in mice of all ages. it has been previously demonstrated that this phenotypic difference is associated with nonstructural protein 3 (nsp3). consensus clones of l10 (designated sfv6) and a7(74) (designated a774wt) were used to construct a panel of recombinant viruses. the insertion of nsp3 from a774wt into the sfv6 backbone had a minor effect on the virulence of the resul ... | 2015 | 26311875 |
| microrna-attenuated clone of virulent semliki forest virus overcomes antiviral type i interferon in resistant mouse ct-2a glioma. | glioblastoma is a terminal disease with no effective treatment currently available. among the new therapy candidates are oncolytic viruses capable of selectively replicating in cancer cells, causing tumor lysis and inducing adaptive immune responses against the tumor. however, tumor antiviral responses, primarily mediated by type i interferon (ifn-i), remain a key problem that severely restricts viral replication and oncolysis. we show here that the semliki forest virus (sfv) strain sfv4, which ... | 2015 | 26269187 |
| flavivirus rna synthesis in vitro. | establishment of in vitro systems to study mechanisms of rna synthesis for positive strand rna viruses have been very useful in the past and have shed light on the composition of protein and rna components, optimum conditions, the nature of the products formed, cis-acting rna elements and trans-acting protein factors required for efficient synthesis. in this review, we summarize our current understanding regarding the requirements for flavivirus rna synthesis in vitro. we describe details of rea ... | 2015 | 26272247 |
| haploid genetic screen reveals a profound and direct dependence on cholesterol for hantavirus membrane fusion. | hantaviruses cause hemorrhagic fever with renal syndrome (hfrs) in the old world and a highly fatal hantavirus cardiopulmonary syndrome (hcps) in the new world. no vaccines or antiviral therapies are currently available to prevent or treat hantavirus disease, and gaps in our understanding of how hantaviruses enter cells challenge the search for therapeutics. we performed a haploid genetic screen in human cells to identify host factors required for entry by andes virus, a highly virulent new worl ... | 2015 | 26126854 |
| a novel system for visualizing alphavirus assembly. | alphaviruses are small, enveloped rna viruses that form infectious particles by budding through the cellular plasma membrane. to help visualize and understand the intracellular assembly of alphavirus virions we have developed a bimolecular fluorescence complementation-based system (bifc) that allows visualization of capsid and e2 subcellular localization and association in live cells. in this system, n- or c-terminal venus fluorescent protein fragments (vn- and vc-) are fused to the n-terminus o ... | 2015 | 26122073 |
| distinct sets of piwi proteins produce arbovirus and transposon-derived pirnas in aedes aegypti mosquito cells. | the piwi-interacting rna (pirna) pathway is essential for transposon silencing in many model organisms. its remarkable efficiency relies on a sophisticated amplification mechanism known as the ping-pong loop. in alphavirus-infected aedes mosquitoes, pirnas with sequence features that suggest ping-pong-dependent biogenesis are produced from viral rna. the piwi family in aedes mosquitoes is expanded when compared to other model organisms, raising the possibility that individual piwi proteins have ... | 2015 | 26068474 |
| mrna capping by venezuelan equine encephalitis virus nsp1: functional characterization and implications for antiviral research. | alphaviruses are known to possess a unique viral mrna capping mechanism involving the viral nonstructural protein nsp1. this enzyme harbors methyltransferase (mtase) and nsp1 guanylylation (gt) activities catalyzing the transfer of the methyl group from s-adenosylmethionine (adomet) to the n7 position of a gtp molecule followed by the formation of an m(7)gmp-nsp1 adduct. subsequent transfer of m(7)gmp onto the 5' end of the viral mrna has not been demonstrated in vitro yet. here we report the bi ... | 2015 | 26041283 |
| conformational changes required for reovirus cell entry are sensitive to ph. | during cell entry, reovirus particles disassemble to generate isvps. isvps undergo conformational changes to form isvp(*) and this conversion is required for membrane penetration. in tissues where isvp formation occurs within endosomes, isvp-to-isvp(*) conversion occurs at low ph. in contrast, in tissues where isvp formation occurs extracellularly, isvp-to-isvp(*) transition occurs at neutral ph. whether these two distinct ph environments influence the efficiency of cell entry is not known. in t ... | 2015 | 26004253 |
| the broad-spectrum antiviral protein zap restricts human retrotransposition. | intrinsic immunity describes the set of recently discovered but poorly understood cellular mechanisms that specifically target viral pathogens. their discovery derives in large part from intensive studies of hiv and siv that revealed restriction factors acting at various stages of the retroviral life cycle. recent studies indicate that some factors restrict both retroviruses and retrotransposons but surprisingly in ways that may differ. we screened known interferon-stimulated antiviral proteins ... | 2015 | 26001115 |
| antiviral antibody profiling by high-density protein arrays. | viral infections elicit antiviral antibodies and have been associated with various chronic diseases. detection of these antibodies can facilitate diagnosis, treatment of infection, and understanding of the mechanisms of virus-associated diseases. in this work, we assayed antiviral antibodies using a novel high-density nucleic acid programmable protein array (hd-nappa) platform. individual viral proteins were expressed in situ directly from plasmids encoding proteins in an array of microscopic re ... | 2015 | 25758251 |
| enhancement of enveloped virus entry by phosphatidylserine. | enveloped virus vectors are used in a wide variety of applications. we have discovered that treatment of cultured cells with phosphatidylserine (ps) liposomes can increase virus vector infection by up to 20-fold. this effect does not abrogate virus receptor requirements, is specific to ps compared to other phospholipids, and is limited to enveloped viruses. furthermore, the enhancement of infection does not occur through increases in virus receptor levels or virus binding, indicating that virus ... | 0 | 16103200 |
| antiviral silencing in animals. | rna silencing or rna interference (rnai) refers to the small rna-guided gene silencing mechanism conserved in a wide range of eukaryotic organisms from plants to mammals. as part of this special issue on the biology, mechanisms and applications of rnai, here we review the recent advances on defining a role of rnai in the responses of invertebrate and vertebrate animals to virus infection. approximately 40 mirnas and 10 rnai suppressors encoded by diverse mammalian viruses have been identified. a ... | 2005 | 16154568 |
| virus entry, assembly, budding, and membrane rafts. | as intracellular parasites, viruses rely heavily on the use of numerous cellular machineries for completion of their replication cycle. the recent discovery of the heterogeneous distribution of the various lipids within cell membranes has led to the proposal that sphingolipids and cholesterol tend to segregate in microdomains called membrane rafts. the involvement of membrane rafts in biosynthetic traffic, signal transduction, and endocytosis has suggested that viruses may also take advantage of ... | 0 | 12794191 |
| nucleocapsid-independent specific viral rna packaging via viral envelope protein and viral rna signal. | for any of the enveloped rna viruses studied to date, recognition of a specific rna packaging signal by the virus's nucleocapsid (n) protein is the first step described in the process of viral rna packaging. in the murine coronavirus a selective interaction between the viral transmembrane envelope protein m and the viral ribonucleoprotein complex, composed of n protein and viral rna containing a short cis-acting rna element, the packaging signal, determines the selective rna packaging into virus ... | 0 | 12584316 |
| chikungunya virus (chikv) inhibitors from natural sources: a medicinal chemistry perspective. | chikungunya virus (chikv) is one of the re-emerging "neglected" tropical diseases whose recent outbreak affected not only africa and south-east asia but also several parts of america and europe. to date, despite its serious nature, no antivirals or vaccines were developed in order to counter this resurgent infectious disease. the recent advancement in crystallography and availability of crystal structures of certain domains of chikv initiates the development of anti-chikv agents using structure- ... | 2015 | 25921858 |
| sequence analysis reveals a conserved extension in the capping enzyme of the alphavirus supergroup, and a homologous domain in nodaviruses. | members of the alphavirus supergroup include human pathogens such as chikungunya virus, hepatitis e virus and rubella virus. they encode a capping enzyme with methyltransferase-guanylyltransferase (mtase-gtase) activity, which is an attractive drug target owing to its unique mechanism. however, its experimental study has proven very difficult. | 2015 | 25886938 |
| rna interference-mediated antiviral defense in insects. | small interfering rna (sirna)-mediated rna interference (rnai) pathways are critical for the detection and inhibition of rna virus replication in insects. recent work has also implicated rnai pathways in the establishment of persistent virus infections and in the control of dna virus replication. accumulating evidence suggests that diverse double-stranded rnas produced by rna and dna viruses can trigger rnai responses yet many viruses have evolved mechanisms to inhibit rnai defenses. therefore, ... | 0 | 26034705 |
| rna degradation in antiviral immunity and autoimmunity. | post-transcriptional control determines the fate of cellular rna molecules. nonsense-mediated decay (nmd) provides quality control of mrna, targeting faulty cellular transcripts for degradation by multiple nucleases including the rna exosome. recent findings have revealed a role for nmd in targeting viral rna molecules, thereby restricting virus infection. interestingly, nmd is also linked to immune responses at another level: mutations affecting the nmd or rna exosome machineries cause chronic ... | 2015 | 25709093 |
| emerging roles for rna degradation in viral replication and antiviral defense. | viral replication significantly alters the gene expression landscape of infected cells. many of these changes are driven by viral manipulation of host transcription or translation machinery. several mammalian viruses encode factors that broadly dampen gene expression by directly targeting messenger rna (mrna). here, we highlight how these factors promote mrna degradation to globally regulate both host and viral gene expression. although these viral factors are not homologous and use distinct mec ... | 2015 | 25721579 |
| the role of rna interference (rnai) in arbovirus-vector interactions. | rna interference (rnai) was shown over 18 years ago to be a mechanism by which arbovirus replication and transmission could be controlled in arthropod vectors. during the intervening period, research on rnai has defined many of the components and mechanisms of this antiviral pathway in arthropods, yet a number of unexplored questions remain. rnai refers to rna-mediated regulation of gene expression. originally, the term described silencing of endogenous genes by introduction of exogenous double- ... | 2015 | 25690800 |
| viral and cellular proteins containing fgdf motifs bind g3bp to block stress granule formation. | the ras-gap sh3 domain-binding proteins (g3bp) are essential regulators of the formation of stress granules (sg), cytosolic aggregates of proteins and rna that are induced upon cellular stress, such as virus infection. many viruses, including semliki forest virus (sfv), block sg induction by targeting g3bp. in this work, we demonstrate that the g3bp-binding motif of sfv nsp3 consists of two fgdf motifs, in which both phenylalanine and the glycine residue are essential for binding. in addition, w ... | 2015 | 25658430 |
| stress granule components g3bp1 and g3bp2 play a proviral role early in chikungunya virus replication. | stress granules (sgs) are protein-mrna aggregates that are formed in response to environmental stresses, resulting in translational inhibition. sgs are generally believed to play an antiviral role and are manipulated by many viruses, including various alphaviruses. gtpase-activating protein (sh3 domain)-binding protein 1 (g3bp1) is a key component and commonly used marker of sgs. its homolog g3bp2 is a less extensively studied sg component. here, we demonstrate that chikungunya virus (chikv) inf ... | 2015 | 25653451 |
| atp1a1-mediated src signaling inhibits coronavirus entry into host cells. | in addition to transporting ions, the multisubunit na(+),k(+)-atpase also functions by relaying cardiotonic steroid (cts)-binding-induced signals into cells. in this study, we analyzed the role of na(+),k(+)-atpase and, in particular, of its atp1a1 α subunit during coronavirus (cov) infection. as controls, the vesicular stomatitis virus (vsv) and influenza a virus (iav) were included. using gene silencing, the atp1a1 protein was shown to be critical for infection of cells with murine hepatitis v ... | 2015 | 25653449 |
| seroepidemiology of selected arboviruses in febrile patients visiting selected health facilities in the lake/river basin areas of lake baringo, lake naivasha, and tana river, kenya. | arboviruses cause emerging and re-emerging infections affecting humans and animals. they are spread primarily by blood-sucking insects such as mosquitoes, ticks, midges, and sandflies. changes in climate, ecology, demographic, land-use patterns, and increasing global travel have been linked to an upsurge in arboviral disease. outbreaks occur periodically followed by persistent low-level circulation. | 0 | 25700043 |
| bovine lactoferrin inhibits toscana virus infection by binding to heparan sulphate. | toscana virus is an emerging sandfly-borne bunyavirus in mediterranean europe responsible for neurological diseases in humans. it accounts for about 80% of paediatric meningitis cases during the summer. despite the important impact of toscana virus infection-associated disease on human health, currently approved vaccines or effective antiviral treatments are not available. in this research, we have analyzed the effect of bovine lactoferrin, a bi-globular iron-binding glycoprotein with potent ant ... | 2015 | 25643293 |
| initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mrna. | translation initiation of alphavirus subgenomic mrna (sgmrna) can occur in the absence of several initiation factors (eifs) in infected cells; however, the precise translation mechanism is still poorly understood. in this study, we have examined the mechanism of initiation and aug selection in sindbis virus (sinv) sgmrna. our present findings suggest that sgmrna is translated via a scanning mechanism, since the presence of a hairpin structure before the initiation codon hampers protein synthesis ... | 2014 | 25404563 |
| mutations conferring a noncytotoxic phenotype on chikungunya virus replicons compromise enzymatic properties of nonstructural protein 2. | chikungunya virus (chikv) (genus alphavirus) has a positive-sense rna genome. chikv nonstructural protein 2 (nsp2) proteolytically processes the viral nonstructural polyprotein, possesses nucleoside triphosphatase (ntpase), rna triphosphatase, and rna helicase activities, and induces cytopathic effects in vertebrate cells. although alphaviral nsp2 mutations can result in a noncytotoxic phenotype, the effects of such mutations on nsp2 enzymatic activities are not well understood. in this study, w ... | 2014 | 25552719 |
| emerging roles of interferon-stimulated genes in the innate immune response to hepatitis c virus infection. | infection with hepatitis c virus (hcv), a major viral cause of chronic liver disease, frequently progresses to steatosis and cirrhosis, which can lead to hepatocellular carcinoma. hcv infection strongly induces host responses, such as the activation of the unfolded protein response, autophagy and the innate immune response. upon hcv infection, the host induces the interferon (ifn)-mediated frontline defense to limit virus replication. conversely, hcv employs diverse strategies to escape host inn ... | 2014 | 25544499 |
| heparan sulfate proteoglycan: an arbovirus attachment factor integral to mosquito salivary gland ducts. | variants of the prototype alphavirus, sindbis (sinv), were used in per os infections of adult female mosquitoes to investigate arbovirus interaction with the salivary gland (sg). infection of aedine mosquitoes with ar339, a heparan sulfate proteoglycan (hspg)-dependent variant, resulted in gross pathology in the sg lateral lobes while infection with tr339, a hspg-independent variant, resulted in minimal sg pathology. hspg was detected in the internal ducts of the sg lateral lobes by immunolabeli ... | 2014 | 25533661 |
| repertoire of virus-derived small rnas produced by mosquito and mammalian cells in response to dengue virus infection. | rna interference (rnai) is the major defense of many arthropods against arthropod-borne rna viruses (arboviruses), but the role of rnai in vertebrate immunity to arboviruses is not clear. rna viruses can trigger rnai in vertebrate cells, but the vertebrate interferon response may obscure this interaction. we quantified virus-derived small rnas (vrnas) generated by mosquito (u4.4) cells and interferon-deficient (vero) and interferon-competent (huh-7) mammalian cells infected with a single isolate ... | 2014 | 25528416 |
| ph-dependent entry of chikungunya virus fusion into mosquito cells. | millions of human infections caused by arthropod-borne pathogens are initiated by the feeding of an infected mosquito on a vertebrate. however, interactions between the viruses and the mosquito vector, which facilitates successful infection and transmission of virus to a subsequent vertebrate host, are still not fully understood. | 2014 | 25476236 |
| host control of insect endogenous retroviruses: small rna silencing and immune response. | endogenous retroviruses are relics of ancient infections from retroviruses that managed to integrate into the genome of germline cells and remained vertically transmitted from parent to progeny. subsequent to the endogenization process, these sequences can move and multiply in the host genome, which can have deleterious consequences and disturb genomic stability. natural selection favored the establishment of silencing pathways that protect host genomes from the activity of endogenous retrovirus ... | 2014 | 25412365 |
| trans-protease activity and structural insights into the active form of the alphavirus capsid protease. | the alphavirus capsid protein (cp) is a serine protease that possesses cis-proteolytic activity essential for its release from the nascent structural polyprotein. the released cp further participates in viral genome encapsidation and nucleocapsid core formation, followed by its attachment to glycoproteins and virus budding. thus, protease activity of the alphavirus capsid is a potential antialphaviral target to arrest capsid release, maturation, and structural polyprotein processing. however, th ... | 2014 | 25100849 |
| screening and large-scale expression of membrane proteins in mammalian cells for structural studies. | structural, biochemical and biophysical studies of eukaryotic membrane proteins are often hampered by difficulties in overexpression of the candidate molecule. baculovirus transduction of mammalian cells (bacmam), although a powerful method to heterologously express membrane proteins, can be cumbersome for screening and expression of multiple constructs. we therefore developed plasmid eric gouaux (peg) bacmam, a vector optimized for use in screening assays, as well as for efficient production of ... | 2014 | 25299155 |
| identification and characterization of alphavirus m1 as a selective oncolytic virus targeting zap-defective human cancers. | oncolytic virotherapy is a growing treatment modality that uses replicating viruses as selective antineoplastic agents. safety and efficacy considerations dictate that an ideal oncolytic agent would discriminate between normal and cancer cells on the basis of common genetic abnormalities in human cancers. here, we identify a naturally occurring alphavirus (m1) as a novel selective killer targeting zinc-finger antiviral protein (zap)-deficient cancer cells. in vitro, in vivo, and ex vivo studies ... | 2014 | 25288727 |
| novel indole-2-carboxamide compounds are potent broad-spectrum antivirals active against western equine encephalitis virus in vivo. | neurotropic alphaviruses, including western, eastern, and venezuelan equine encephalitis viruses, cause serious and potentially fatal central nervous system infections in humans for which no currently approved therapies exist. we previously identified a series of thieno[3,2-b]pyrrole derivatives as novel inhibitors of neurotropic alphavirus replication, using a cell-based phenotypic assay (w. peng et al., j. infect. dis. 199:950-957, 2009, doi:http://dx.doi.org/10.1086/597275), and subsequently ... | 2014 | 25031353 |
| the composition of west nile virus lipid envelope unveils a role of sphingolipid metabolism in flavivirus biogenesis. | west nile virus (wnv) is an emerging zoonotic mosquito-borne flavivirus responsible for outbreaks of febrile illness and meningoencephalitis. the replication of wnv takes place on virus-modified membranes from the endoplasmic reticulum of the host cell, and virions acquire their envelope by budding into this organelle. consistent with this view, the cellular biology of this pathogen is intimately linked to modifications of the intracellular membranes, and the requirement for specific lipids, suc ... | 2014 | 25122799 |
| role of micrornas in arbovirus/vector interactions. | the role of micrornas (mirnas) as small non-coding rnas in regulation of gene expression has been recognized. they appear to be involved in regulation of a wide range of cellular pathways that affect several biological processes such as development, the immune system, survival, metabolism and host-pathogen interactions. arthropod-borne viruses impose great economic and health risks around the world. recent advances in mirna biology have shed some light on the role of these small rnas in vector-v ... | 2014 | 25251636 |
| picornavirus morphogenesis. | the picornaviridae represent a large family of small plus-strand rna viruses that cause a bewildering array of important human and animal diseases. morphogenesis is the least-understood step in the life cycle of these viruses, and this process is difficult to study because encapsidation is tightly coupled to genome translation and rna replication. although the basic steps of assembly have been known for some time, very few details are available about the mechanism and factors that regulate this ... | 0 | 25184560 |
| locking and blocking the viral landscape of an alphavirus with neutralizing antibodies. | alphaviruses are serious, sometimes lethal human pathogens that belong to the family togaviridae. the structures of human venezuelan equine encephalitis virus (veev), an alphavirus, in complex with two strongly neutralizing antibody fab fragments (f5 and 3b4c-4) have been determined using a combination of cryo-electron microscopy and homology modeling. we characterize these monoclonal antibody fab fragments, which are known to abrogate veev infectivity by binding to the e2 (envelope) surface gly ... | 2014 | 24920796 |
| antiviral responses of arthropod vectors: an update on recent advances. | arthropod vectors, such as mosquitoes, ticks, biting midges and sand flies, transmit many viruses that can cause outbreaks of disease in humans and animals around the world. arthropod vector species are invading new areas due to globalisation and environmental changes, and contact between exotic animal species, humans and arthropod vectors is increasing, bringing with it the regular emergence of new arboviruses. for future strategies to control arbovirus transmission, it is important to improve ... | 2014 | 25674592 |
| an alphavirus-based adjuvant enhances serum and mucosal antibodies, t cells, and protective immunity to influenza virus in neonatal mice. | neonatal immune responses to infection and vaccination are biased toward th2 at the cost of proinflammatory th1 responses needed to combat intracellular pathogens. however, upon appropriate stimulation, the neonatal immune system can induce adult-like th1 responses. here we report that a new class of vaccine adjuvant is especially well suited to enhance early life immunity. the gvi3000 adjuvant is a safe, nonpropagating, truncated derivative of venezuelan equine encephalitis virus that targets d ... | 2014 | 24899195 |
| characterization of aedes aegypti innate-immune pathways that limit chikungunya virus replication. | replication of arboviruses in their arthropod vectors is controlled by innate immune responses. the rna sequence-specific break down mechanism, rna interference (rnai), has been shown to be an important innate antiviral response in mosquitoes. in addition, immune signaling pathways have been reported to mediate arbovirus infections in mosquitoes; namely the jak/stat, immune deficiency (imd) and toll pathways. very little is known about these pathways in response to chikungunya virus (chikv) infe ... | 2014 | 25058001 |
| expanding the proteome of an rna virus by phosphorylation of an intrinsically disordered viral protein. | the human proteome contains myriad intrinsically disordered proteins. within intrinsically disordered proteins, polyproline-ii motifs are often located near sites of phosphorylation. we have used an unconventional experimental paradigm to discover that phosphorylation by protein kinase a (pka) occurs in the intrinsically disordered domain of hepatitis c virus non-structural protein 5a (ns5a) on thr-2332 near one of its polyproline-ii motifs. phosphorylation shifts the conformational ensemble of ... | 2014 | 25031324 |
| a small molecule inhibits virion attachment to heparan sulfate- or sialic acid-containing glycans. | primary attachment to cellular glycans is a critical entry step for most human viruses. some viruses, such as herpes simplex virus type 1 (hsv-1) and hepatitis c virus (hcv), bind to heparan sulfate, whereas others, such as influenza a virus (iav), bind to sialic acid. receptor mimetics that interfere with these interactions are active against viruses that bind to either heparan sulfate or to sialic acid. however, no molecule that inhibits the attachment of viruses in both groups has yet been id ... | 2014 | 24789779 |
| undiagnosed acute viral febrile illnesses, sierra leone. | sierra leone in west africa is in a lassa fever-hyperendemic region that also includes guinea and liberia. each year, suspected lassa fever cases result in submission of ≈500-700 samples to the kenema government hospital lassa diagnostic laboratory in eastern sierra leone. generally only 30%-40% of samples tested are positive for lassa virus (lasv) antigen and/or lasv-specific igm; thus, 60%-70% of these patients have acute diseases of unknown origin. to investigate what other arthropod-borne an ... | 0 | 24959946 |
| high efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model. | the combination of virotherapy and chemotherapy may enable efficient tumor regression that would be unachievable using either therapy alone. in this study, we investigated the efficiency of transgene delivery and the cytotoxic effects of alphaviral vector in combination with 5-fluorouracil (5-fu) in a mouse mammary tumor model (4 t1). | 2014 | 24950740 |
| exploration of panviral proteome: high-throughput cloning and functional implications in virus-host interactions. | throughout the long history of virus-host co-evolution, viruses have developed delicate strategies to facilitate their invasion and replication of their genome, while silencing the host immune responses through various mechanisms. the systematic characterization of viral protein-host interactions would yield invaluable information in the understanding of viral invasion/evasion, diagnosis and therapeutic treatment of a viral infection, and mechanisms of host biology. with more than 2,000 viral ge ... | 2014 | 24955142 |
| ebolavirus entry requires a compact hydrophobic fist at the tip of the fusion loop. | ebolavirus is an enveloped virus causing severe hemorrhagic fever. its surface glycoproteins undergo proteolytic cleavage and rearrangements to permit membrane fusion and cell entry. here we focus on the glycoprotein's internal fusion loop (fl), critical for low-ph-triggered fusion in the endosome. alanine mutations at l529 and i544 and particularly the l529 i544 double mutation compromised viral entry and fusion. the nuclear magnetic resonance (nmr) structures of the i544a and l529a i544a mutan ... | 2014 | 24696482 |
| self-assembly approaches to nanomaterial encapsulation in viral protein cages. | a perspective on abiotic material encapsulation inside virus capsids is provided. the emphasis is on the physical principles of virus assembly relevant to packaging, strategies for encapsulation and capsid modification, and on emerging applications. | 0 | 19809586 |
| structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. | recent work has identified three distinct classes of viral membrane fusion proteins based on structural criteria. in addition, there are at least four distinct mechanisms by which viral fusion proteins can be triggered to undergo fusion-inducing conformational changes. viral fusion proteins also contain different types of fusion peptides and vary in their reliance on accessory proteins. these differing features combine to yield a rich diversity of fusion proteins. yet despite this staggering div ... | 0 | 18568847 |
| uncoupling rna virus replication from transcription via the polymerase: functional and evolutionary insights. | many eukaryotic positive-strand rna viruses transcribe subgenomic (sg) mrnas that are virus-derived messages that template the translation of a subset of viral proteins. currently, the premature termination (pt) mechanism of sg mrna transcription, a process thought to operate in a variety of viruses, is best understood in tombusviruses. the viral rna elements involved in regulating this mechanism have been well characterized in several systems; however, no corresponding protein factors have been ... | 2007 | 18034156 |
| viral encounters with 2',5'-oligoadenylate synthetase and rnase l during the interferon antiviral response. | | 2007 | 17804500 |
| the glycoprotein cytoplasmic tail of uukuniemi virus (bunyaviridae) interacts with ribonucleoproteins and is critical for genome packaging. | we have analyzed the importance of specific amino acids in the cytoplasmic tail of the glycoprotein g(n) for packaging of ribonucleoproteins (rnps) into virus-like particles (vlps) of uukuniemi virus (uuk virus), a member of the bunyaviridae family. in order to study packaging, we added the g(n)/g(c) glycoprotein precursor (p110) to a polymerase i-driven minigenome rescue system to generate vlps that are released into the supernatant. these particles can infect new cells, and reporter gene expre ... | 2007 | 17229712 |
| mitochondrial bioenergetic alterations in mouse neuroblastoma cells infected with sindbis virus: implications to viral replication and neuronal death. | the metabolic resources crucial for viral replication are provided by the host. details of the mechanisms by which viruses interact with host metabolism, altering and recruiting high free-energy molecules for their own replication, remain unknown. sindbis virus, the prototype of and most widespread alphavirus, causes outbreaks of arthritis in humans and serves as a model for the study of the pathogenesis of neurological diseases induced by alphaviruses in mice. in this work, respirometric analys ... | 2012 | 22485151 |
| superior induction of t cell responses to conserved hiv-1 regions by electroporated alphavirus replicon dna compared to that with conventional plasmid dna vaccine. | vaccination using "naked" dna is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. previously, we constructed dna-launched semliki forest virus replicons (drep), which stimulate pattern recognition receptors and induce augmented immune responses. also, in vivo electroporation was shown to enhance immune responses induced by conventional dna vaccines. here, we combine these two approaches and show that in vivo ... | 2012 | 22318135 |
| interferon-β sensitivity of tumor cells correlates with poor response to va7 virotherapy in mouse glioma models. | in our recent study, replicative alphaviral vector va7 was found to be effective against orthotopic human u87-glioma xenografts in an athymic mouse model eradicating the tumors with single intravenous (i.v.) injection. here, we tested the efficacy of va7 in immunocompetent orthotopic gl261 and ct-2a glioma models of c57bl/6 mouse in vivo. the cell lines were susceptible to va7 infection in vitro, but gl261 infection was highly restricted in confluent cell cultures, and mouse interferon-β (ifnβ) ... | 2012 | 22434140 |
| regulation of stress granules in virus systems. | virus infection initiates a number of cellular stress responses that modulate gene regulation and compartmentalization of rna. viruses must control host gene expression and the localization of viral rnas to be successful parasites. rna granules such as stress granules and processing bodies (pbs) contain translationally silenced messenger ribonucleoproteins (mrnps) and serve as extensions of translation regulation in cells, storing transiently repressed mrnas. new reports show a growing number of ... | 2012 | 22405519 |
| effective virus inactivation and removal by steps of biotest pharmaceuticals igiv production process. | the virus validation of three steps of biotest pharmaceuticals igiv production process is described here. the steps validated are precipitation and removal of fraction iii of the cold ethanol fractionation process, solvent/detergent treatment and 35 nm virus filtration. virus validation was performed considering combined worst case conditions. by these validated steps sufficient virus inactivation/removal is achieved, resulting in a virus safe product. | 2012 | 24371563 |
| oncolytic virotherapy in veterinary medicine: current status and future prospects for canine patients. | oncolytic viruses refer to those that are able to eliminate malignancies by direct targeting and lysis of cancer cells, leaving non-cancerous tissues unharmed. several oncolytic viruses including adenovirus strains, canine distemper virus and vaccinia virus strains have been used for canine cancer therapy in preclinical studies. however, in contrast to human studies, clinical trials with oncolytic viruses for canine cancer patients have not been reported. an 'ideal' virus has yet to be identifie ... | 2012 | 22216938 |
| the cell biology of receptor-mediated virus entry. | the cell imposes multiple barriers to virus entry. however, viruses exploit fundamental cellular processes to gain entry to cells and deliver their genetic cargo. virus entry pathways are largely defined by the interactions between virus particles and their receptors at the cell surface. these interactions determine the mechanisms of virus attachment, uptake, intracellular trafficking, and, ultimately, penetration to the cytosol. elucidating the complex interplay between viruses and their recept ... | 2011 | 22123832 |
| function of membrane rafts in viral lifecycles and host cellular response. | membrane rafts are small (10-200 nm) sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. membrane rafts play an important role in viral infection cycles and viral virulence. viruses are divided into four main classes, enveloped dna virus, enveloped rna virus, nonenveloped dna virus, and nonenveloped rna virus. general virus infection cycle is also classified into two sections, the early stage (entry process) and the late stage (assembly, budding, and release proce ... | 2011 | 22191032 |
| interferon-stimulated genes and their antiviral effector functions. | many viruses trigger the type i interferon (ifn) system, leading to the transcription of hundreds of interferon-stimulated genes (isgs). the products of these isgs exert numerous antiviral effector functions, many of which are still not fully described. recent efforts have been aimed at identifying which isgs are antiviral and further characterizing their mechanisms of action. ifn effectors vary widely in their magnitude of inhibitory activity and display combinatorial antiviral properties. coll ... | 0 | 22328912 |
| crystallization, high-resolution data collection and preliminary crystallographic analysis of aura virus capsid protease and its complex with dioxane. | the c-terminal protease domain of capsid protein from aura virus expressed in a bacterial expression system has been purified to homogeneity and crystallized. crystals suitable for x-ray diffraction analysis were obtained by the vapour-diffusion method using 0.1 m bis-tris and polyethylene glycol monomethyl ether 2000. crystals of the c-terminal protease domain of capsid protein in complex with dioxane were also produced and crystal data were obtained. both crystals belonged to space group c2, w ... | 2011 | 22102240 |
| stress granules and virus replication. | viruses are dependent on the cellular translation machinery for protein synthesis. part of the innate immune response to infection is activation of the stress kinase pkr which phosphorylates the alpha subunit of the initiation factor eif2. this results in inhibition of translation and is intended to block virus replication. a downstream effect of translational shutoff involves the formation of cytoplasmic granules, termed stress granules (sgs), that contain mrnas, initiation factors, ribosomal s ... | 0 | 26388931 |
| factors supporting intrathecal humoral responses following viral encephalomyelitis. | central nervous system (cns) infections and autoimmune inflammatory disorders are often associated with retention of antibody-secreting cells (asc). although beneficial or detrimental contributions of asc to cns diseases remain to be defined, virus-specific asc are crucial in controlling persistent cns infection following coronavirus-induced encephalomyelitis. this report characterizes expression kinetics of factors associated with asc homing, differentiation, and survival in the spinal cord, th ... | 2010 | 21191015 |
| novel viral vector systems for gene therapy. | | 2010 | 21994667 |
| antiviral actions of interferons. | tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (ifns), as well as strategies evolved by viruses to antagonize the actions of ifns. furthermore, advances made while elucidating the ifn system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecula ... | 0 | 11585785 |
| anti-viral rna silencing: do we look like plants? | the anti-viral function of rna silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. it appears that, whereas the anti-viral process seems to be similarly ... | 2006 | 16409629 |
| classical nucleation theory of virus capsids. | a fundamental step in the replication of a viral particle is the self-assembly of its rigid shell (capsid) from its constituent proteins. capsids play a vital role in genome replication and intercellular movement of viruses, and as such, understanding viral assembly has great potential in the development of new antiviral therapies and a systematic treatment of viral infection. in this article, we assume that nucleation is the underlying mechanism for self-assembly and combine the theoretical met ... | 2005 | 16387781 |
| autophagy in cell death: an innocent convict? | the visualization of autophagosomes in dying cells has led to the belief that autophagy is a nonapoptotic form of programmed cell death. this concept has now been evaluated using cells and organisms deficient in autophagy genes. most evidence indicates that, at least in cells with intact apoptotic machinery, autophagy is primarily a pro-survival rather than a pro-death mechanism. this review summarizes the evidence linking autophagy to cell survival and cell death, the complex interplay between ... | 0 | 16200202 |
| bax-like protein drob-1 protects neurons from expanded polyglutamine-induced toxicity in drosophila. | bcl-2 family proteins regulate cell death through the mitochondrial apoptotic pathway. here, we show that the drosophila bax-like bcl-2 family protein drob-1 maintains mitochondrial function to protect cells from neurodegeneration. a pan-neuronal knockdown of drob-1 results in lower locomotor activity and a shorter lifespan in adult flies. either the rnai-mediated downregulation of drob-1 or overexpression of drob-1 antagonist buffy strongly enhances the polyglutamine-induced accumulation of ubi ... | 2005 | 16001086 |
| flaviviruses are sensitive to inhibition of thymidine synthesis pathways. | dengue virus has emerged as a global health threat to over one-third of humankind. as a positive-strand rna virus, dengue virus relies on the host cell metabolism for its translation, replication, and egress. therefore, a better understanding of the host cell metabolic pathways required for dengue virus infection offers the opportunity to develop new approaches for therapeutic intervention. in a recently described screen of known drugs and bioactive molecules, we observed that methotrexate and f ... | 2013 | 23824813 |
| encephalomyocarditis virus disrupts stress granules, the critical platform for triggering antiviral innate immune responses. | in response to stress, cells induce ribonucleoprotein aggregates, termed stress granules (sgs). sgs are transient loci containing translation-stalled mrna, which is eventually degraded or recycled for translation. infection of some viruses, including influenza a virus with a deletion of nonstructural protein 1 (iavδns1), induces sg-like protein aggregates. previously, we showed that iavδns1-induced sgs are required for efficient induction of type i interferon (ifn). here, we investigated sg form ... | 2013 | 23785203 |