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occurrence of pathogens in wild rodents caught on swedish pig and chicken farms.a total of 207 wild rodents were caught on nine pig farms, five chicken farms and five non-farm locations in sweden and surveyed for a selection of bacteria, parasites and viruses. lawsonia intracellularia and pathogenic yersinia enterocolitica were only detected in rodents on pig farms (9% and 8% prevalence, respectively) which indicate that these agents are more likely to be transmitted to rodents from pigs or the environment on infected farms. brachyspira hyodysenteriae (1%), brachyspira inte ...201323174339
atp hydrolysis enhances rna recognition and antiviral signal transduction by the innate immune sensor, laboratory of genetics and physiology 2 (lgp2).laboratory of genetics and physiology 2 (lgp2) is a member of the rig-i-like receptor family of cytoplasmic pattern recognition receptors that detect molecular signatures of virus infection and initiate antiviral signal transduction cascades. the atp hydrolysis activity of lgp2 is essential for antiviral signaling, but it has been unclear how the enzymatic properties of lgp2 regulate its biological response. quantitative analysis of the dsrna binding and enzymatic activities of lgp2 revealed hig ...201323184951
phosphorylation of eif2α is responsible for the failure of the picornavirus internal ribosome entry site to direct translation from sindbis virus replicons.translation directed by the poliovirus (pv) or encephalomyocarditis virus (emcv) internal ribosome entry site (ires) is very inefficient when expressed from sindbis virus (sv) replicons. this inhibition can be rescued by co-expression of pv 2a protease (2a(pro)). inhibition correlates with the extensive phosphorylation of eukaryotic initiation factor (eif) 2α induced by sv replication. confirmation that pv or emcv ires-driven translation can function when eif2α is not phosphorylated was obtained ...201323255624
cardiac-specific overexpression of melanoma differentiation-associated gene-5 protects mice from lethal viral myocarditis.viral myocarditis is among the most common causes of heart failure in children and young adults. the rna helicase melanoma differentiation-associated gene-5 (mda5) is critical for host antiviral responses against members of the picornaviridae family, such as encephalomyocarditis virus (emcv). mda5-knockout mice are highly susceptible to emcv infection and develop significant myocardial injury and left ventricular dysfunction. however, the mechanisms by which mda5 signaling within cardiac myocyte ...201223271791
quinacrine impairs enterovirus 71 rna replication by preventing binding of polypyrimidine-tract binding protein with internal ribosome entry sites.since the 1980s, epidemics of enterovirus 71 (ev71) and other enteroviruses have occurred in asian countries and regions, causing a wide range of human diseases. no effective therapy is available for the treatment of these infections. internal ribosome entry sites (iress) are indispensable for the initiation of translation in enteroviruses. several cellular factors, as well as the ribosome, are recruited to the conserved ires during this process. quinacrine intercalates into the rna architecture ...201323301007
ires-based venezuelan equine encephalitis vaccine candidate elicits protective immunity in mice.venezuelan equine encephalitis virus (veev) is an arbovirus that causes periodic outbreaks that impact equine and human populations in the americas. one of the veev subtypes located in mexico and central america (ie) has recently been recognized as an important cause of equine disease and death, and human exposure also appears to be widespread. here, we describe the use of an internal ribosome entry site (ires) from encephalomyocarditis virus to stably attenuate veev, creating a vaccine candidat ...201323351391
transient high level mammalian reovirus replication in a bat epithelial cell line occurs without cytopathic effect.mammalian reoviruses exhibit a large host range and infected cells are generally killed; however, most studies examined only a few cell types and host species, and are probably not representative of all possible interactions between virus and host cell. many questions thus remain concerning the nature of cellular factors that affect viral replication and cell death. in the present work, it was observed that replication of the classical mammalian reovirus serotype 3 dearing in a bat epithelial ce ...201323352882
mcpip1 ribonuclease exhibits broad-spectrum antiviral effects through viral rna binding and degradation.monocyte chemoattractant protein 1-induced protein 1 (mcpip1), belonging to the mcpip family with highly conserved ccch-type zinc finger and nedd4-bp1, yacp nuclease domains, has been implicated in negative regulation of the cellular inflammatory responses. in this report, we demonstrate for the first time that this rna-binding nuclease also targets viral rna and possesses potent antiviral activities. overexpression of the human mcpip1, but not mcpip2, mcpip3 or mcpip4, inhibited japanese enceph ...201323355615
validation of an antiviral assay method for quantifying ifn-α5 activity in macaque and human serum.ifn-α5 has been demonstrated to induce stronger signaling and higher expression of antiviral genes than ifn-α2, which is the current treatment in chronic viral hepatitis. however, there is no specific and validated quantification method in order to conduct kinetic studies as part of the preclinical and clinical evaluation for regulatory purposes.201323394696
trim22 inhibits influenza a virus infection by targeting the viral nucleoprotein for degradation.tripartite motif (trim) protein superfamily members are emerging as important effectors of the innate immune response against viral infections. in particular, trim22 was reported to exert antiviral activity against rna viruses, such as hepatitis b virus (hbv), encephalomyocarditis virus (ecmv), and human immunodeficiency virus type 1 (hiv-1). we demonstrate here, for the first time, that trim22 is upregulated by influenza a virus (iav) infection at both mrna and protein levels in human alveolar ...201323408607
co-expression of the bcl-xl antiapoptotic protein enhances the induction of th1-like immune responses in mice immunized with dna vaccines encoding fmdv b and t cell epitopes.foot-and-mouth disease (fmd) is one of the most devastating animal diseases, affecting all cloven-hoofed domestic and wild animal species. previous studies from our group using dna vaccines encoding fmd virus (fmdv) b and t cell epitopes targeted to antigen presenting cells, allowed demonstrating total protection from fmdv homologous challenge in those animals efficiently primed for both humoral and cellular specific responses (borrego et al. antivir res 92:359-363, 2011). in this study, a new d ...201323483312
guanine-nucleotide exchange factor rcc1 facilitates a tight binding between the encephalomyocarditis virus leader and cellular ran gtpase.the leader (l) protein of encephalomyocarditis virus (emcv) shuts off host cell nucleocytoplasmic trafficking (nct) by inducing hyperphosphorylation of nuclear pore proteins. this dramatic effect by a nonenzymatic protein of 6 kda is not well understood but clearly involves l binding to cellular ran gtpase, a critical factor of active nct. exogenous gdp and gtp are inhibitory to l-ran binding, but the guanine-nucleotide exchange factor rcc1 can relieve this inhibition. in the presence of rcc1, l ...201323536659
high pressure treatment under subfreezing temperature results in drastic inactivation of enveloped and non-enveloped viruses.some viruses are sensitive to high pressure. the freeze-pressure generation method (fpgm) applies pressure as high as 250 mpa on a substance, simply by freezing a pressure-resistant reservoir in which the substance is immersed in water. here we examined whether the fpgm successfully inactivates herpes simplex virus type 1 (hsv-1), an enveloped dna virus belonging to the human herpesviridae, and encephalomyocarditis virus (emcv), an envelope-free rna virus belonging to the picornaviridae. after t ...201323609229
a perspective on mammalian upstream open reading frame function.post-transcriptional control makes a major contribution to the overall regulation of gene expression pathway. within the cytoplasm this is mediated by a combination of regulatory rna motifs within the 5' and 3' untranslated regions of mrnas and their interacting protein/rna partners. one of the most common regulatory rna elements in mammalian transcripts (present in approximately 40% of all mrnas) are upstream open reading frames (uorfs). however, despite the prevalence of these rna elements how ...201323624144
analysis of the activity of virus internal ribosome entry site in silkworm bombyx mori.internal ribosome entry site (ires) has been widely used in genetic engineering; however, the application in silkworm (bombyx mori) has hardly been reported. in this study, the biological activity of partial sequence of encephalomyocarditis virus (emcv) ires, rhopalosiphum padi virus (rhpv) ires, and the hybrid of ires of emcv and rhpv were investigated in spodoptera frugiperda (sf9) cell line and silkworm tissues. the hybrid ires of emcv and rhpv showed more effective than emcv ires or rhpv ire ...201323644592
mda5 plays a crucial role in enterovirus 71 rna-mediated irf3 activation.induction of type-i interferons (ifns), ifn-α/β, is crucial to innate immunity against rna virus infection. cytoplasmic retinoic acid-inducible gene i (rig-i)-like receptors, including rig-i and melanoma differentiation-associated gene 5 (mda5), are critical pathogen sensors for activation of type-i ifn expression in response to rna virus infection. mda5 is required for type-i ifn expression in mouse models in response to infection by picornaviruses, such as encephalomyocarditis virus (emcv) and ...201323650567
ires-driven expression of the capsid protein of the venezuelan equine encephalitis virus tc-83 vaccine strain increases its attenuation and safety.the live-attenuated tc-83 strain is the only licensed veterinary vaccine available to protect equids against venezuelan equine encephalitis virus (veev) and to protect humans indirectly by preventing equine amplification. however, tc-83 is reactogenic due to its reliance on only two attenuating point mutations and has infected mosquitoes following equine vaccination. to increase its stability and safety, a recombinant tc-83 was previously engineered by placing the expression of the viral structu ...201323675542
interferon-λ1 linked to a stabilized dimer of fab potently enhances both antitumor and antiviral activities in targeted cells.the type iii interferons (ifns), comprising ifn-λ1, ifn-λ2, and ifn-λ3, behave similarly to ifn-α in eliciting antiviral, antitumor, and immune-modulating activities. due to their more restricted cellular targets, ifn-λs are attractive as potential alternatives to existing therapeutic regimens based on ifn-αs. we have applied the dock-and-lock™ method to improve the anti-proliferative potency of ifn-λ1 up to 1,000-fold in targeted cancer cell lines by tethering stabilized fab dimers, derived fro ...201323696859
encephalomyocarditis virus leader protein hinge domain is responsible for interactions with ran gtpase.encephalomyocarditis virus (emcv), a cardiovirus, initiates its polyprotein with a short 67 amino acid leader (l) sequence. the protein acts as a unique pathogenicity factor, with anti-host activities which include the triggering of nuclear pore complex hyperphosphorylation and direct binding inhibition of the active cellular transport protein, ran gtpase. chemical modifications and protein mutagenesis now map the ran binding domain to the l hinge-linker region, and in particular, to amino acids ...201323711384
serological survey of veterinarians to assess the zoonotic potential of three emerging swine diseases in mexico.we conducted an immunological assay of blood samples taken from 85 swine-specialist veterinarians attending the congress of the mexican association of swine specialist veterinarians in mexico in 2011. serum samples were assayed for porcine rubulavirus (porpv), encephalomyocarditis virus (emcv) and leptospira spp. antibodies. using a hemagglutination inhibition test, we registered 2.3% and 27% seropositivity for porpv and emcv, respectively. using viral neutralization tests, we registered 5.8% an ...201423734711
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 ...201323785203
prevalence of swine viral and bacterial pathogens in rodents and stray cats captured around pig farms in korea.in 2008, 102 rodents and 24 stray cats from the areas around 9 pig farms in northeast south korea were used to determine the prevalence of the following selected swine pathogens: ten viral pathogens [porcine epidemic diarrhea virus (pedv), transmissible gastroenteritis virus (tgev), rotavirus, classical swine fever virus (csfv), porcine circovirus type 2 (pcv2), encephalomyocarditis virus (emcv), porcine reproductive and respiratory syndrome virus (prrsv), porcine parvovirus (ppv), pseudorabies ...201323892461
glucocorticoid receptor ligands modulate cardiovirus encephalomyocarditis virus internal ribosome entry site activity.the use of small molecules to modulate cellular processes is a powerful approach to investigate gene function as a complement to genetic approaches. the discovery and characterization of compounds that modulate translation initiation, the rate-limiting step of protein synthesis, is important both to provide tool compounds to explore this fundamental biological process and to further evaluate protein synthesis as a therapeutic target. while most messenger ribonucleic acids (mrnas) recruit ribosom ...201323906347
a highly divergent encephalomyocarditis virus isolated from nonhuman primates in singapore.in 2001 and 2002, fatal myocarditis resulted in the sudden deaths of four, two adult and two juvenile, orang utans out of a cohort of 26 in the singapore zoological gardens.201323914943
isolation, molecular characterization, and phylogenetic analysis of encephalomyocarditis virus from south china tigers in china.although encephalomyocarditis virus (emcv) can infect many host species and cause myocarditis and sudden death in many species, little is known about emcv infection in tigers. a virus was isolated from organs of dead south china tigers with sudden death in southern china. the production of cytopathic effect on bhk cells, and the results of pcr, electron microscopy (em), and whole genome sequencing indicated that the pathogen was emcv, the strain was named fj13. other pathogenic agents were exclu ...201323917023
efficiency of e2-p7 processing modulates production of infectious hepatitis c virus.previous studies indicate that the processing of hepatitis c virus (hcv) e2-p7-ns2 precursor mediated by host signal peptidase is relatively inefficient, resulting in the accumulation of e2-p7-ns2 and e2-p7 precursors in addition to e2 in mammalian cells. in this study, we discovered that a significant inhibition of the processing at an e2-p7 junction site is detrimental for hcv production, whether it was caused by the mutations in p7 or by the strategic introduction of a mutation at a terminal ...201323946462
chemistry and antiviral activity of arrabidaea pulchra (bignoniaceae).the aim of the present work was to carry out a bioguided isolation of antiviral chemical constituents from an ethanol extract of leaves from arrabidaea pulchra (cham.) sandwith (eeapl) that had shown in vitro activity in a previous screening using dna and rna viruses. the activity of eepal was evaluated against the dna viruses human herpesvirus 1 (hsv-1) and vaccinia virus western reserve (vacv-wr) as well as against the rna viruses murine encephalomyocarditis virus (emcv), and dengue virus 2 (d ...201323959197
encephalomyocarditis virus infection in a splenectomised calf.encephalomyocarditis (emc) caused by emc virus (emcv) was diagnosed in a 5-month-old splenectomised calf, which died suddenly on an experimental farm that had a high infestation of rodents.201323980833
complete nucleotide sequence of encephalomyocarditis virus isolated from south china tigers in china.a strain of encephalomyocarditis virus (emcv), strain fj13, has been isolated from south china tigers in china, and its complete genome has been sequenced and analyzed. phylogenetic analysis suggests that fj13 belongs to the emcv-1 serotype, and it is highly prevalent in china.201323990575
a rt-pcr assay for the detection of encephalomycarditis virus infections in pigs.encephalomyocarditis virus (emcv) infections can cause losses in pig farms all over the world. rapid, sensitive and unequivocal detection of this virus is therefore essential for the diagnosis and control of the disease. an rt-pcr assay was developed, optimized and evaluated for encephalomyocarditis virus detection in organ based on a pair of primers that amplifies a 165 bp dna fragment from a highly conserved nucleotide region of the viral 3d glycoprotein. pcr products of the expected size were ...200924031451
antiviral rna interference in mammalian cells.in antiviral rna interference (rnai), the dicer enzyme processes virus-derived double-stranded rna (dsrna) into small interfering rnas (sirnas) that guide argonaute proteins to silence complementary viral rna. as a counterdefense, viruses deploy viral suppressors of rnai (vsrs). well-established in plants and invertebrates, the existence of antiviral rnai remains unknown in mammals. here, we show that undifferentiated mouse cells infected with encephalomyocarditis virus (emcv) or nodamura virus ...201324115438
a sensitive and specific nanoparticle-assisted pcr assay for rapid detection of porcine parvovirus.a novel nanoparticle-assisted polymerase chain reaction (nanopcr) assay to detect porcine parvovirus (ppv) is described here. primers for this assay were designed based on the conserved region of the nonstructural protein 1 (ns1) gene of ppv, which encodes one of the nonstructural proteins. the sensitivity of the ppv nanopcr assay was measured by using diluted recombinant plasmids in which the ppv ns1 gene had been inserted. the detection limit was 5.6 × 10(1) copies μl(-1) for the ppv nanopcr a ...201424117951
mitochondrial protein mitofusin 2 is required for nlrp3 inflammasome activation after rna virus infection.nod-like receptor family, pyrin domain-containing 3 (nlrp3), is involved in the early stages of the inflammatory response by sensing cellular damage or distress due to viral or bacterial infection. activation of nlrp3 triggers its assembly into a multimolecular protein complex, termed "nlrp3 inflammasome." this event leads to the activation of the downstream molecule caspase-1 that cleaves the precursor forms of proinflammatory cytokines, such as interleukin 1 beta (il-1β) and il-18, and initiat ...201324127597
detection and characterization of potentially zoonotic viruses in faeces of pigs at slaughter in germany.pigs can harbour a variety of viruses in their gastrointestinal tract. some of them are closely related to human viruses and are therefore suspected to have a zoonotic potential. only little is known about the presence of those viruses in pigs at slaughter. however, by contamination of meat with zoonotic viruses during the slaughtering process, food-borne transmission to humans may be possible. here we analyzed 120 faecal samples of pigs at slaughter from 3 different geographical regions of germ ...201424247020
gef-h1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses.detailed understanding of the signaling intermediates that confer the sensing of intracellular viral nucleic acids for induction of type i interferons is critical for strategies to curtail viral mechanisms that impede innate immune defenses. here we show that the activation of the microtubule-associated guanine nucleotide exchange factor gef-h1, encoded by arhgef2, is essential for sensing of foreign rna by rig-i-like receptors. activation of gef-h1 controls rig-i-dependent and mda5-dependent ph ...201424270516
isolation and molecular analysis of porcine encephalomyocarditis virus strain bd2 from northern china.encephalomyocarditis virus (emcv) can cause acute myocarditis in young pigs or reproductive failure in sows. in this study, an emcv strain (bd2) was isolated from the suspected piglets with emcv in china. it was identified by an indirect immunofluorescence assay and reverse-transcription polymerase chain reaction. the virus could reproduce on bhk-21 cells and reach a peak titer by 16 hpi with maximum titers of 10(8.22)tcid50/0.1 ml. phylogenetic analyses of open reading frame and the vp3/vp1 gen ...201424291508
interaction of paramecium caudatum and picornaviruses.in our paper we have researched the relationship between picornaviruses (poliovirus, foot-and-mouth disease virus and encephalomyocarditis virus) and ciliata (paramecium caudatum). we show that the number of paramecium in medium sharply increased during coincubation with picornaviruses within 2-5 days. this cannot be explained only by the fact that viruses were nutrient source for paramecium because in case of inactivated viruses the number of infusorians in medium increased a little. at the sam ...201224293830
internal ribosome entry site-based attenuation of a flavivirus candidate vaccine and evaluation of the effect of beta interferon coexpression on vaccine properties.infectious clone technologies allow the rational design of live attenuated viral vaccines with the possibility of vaccine-driven coexpression of immunomodulatory molecules for additional vaccine safety and efficacy. the latter could lead to novel strategies for vaccine protection against infectious diseases where traditional approaches have failed. here we show for the flavivirus murray valley encephalitis virus (mvev) that incorporation of the internal ribosome entry site (ires) of encephalomyo ...201324307589
encephalomyocarditis virus leader is phosphorylated by ck2 and syk as a requirement for subsequent phosphorylation of cellular nucleoporins.encephalomyocarditis virus and theilovirus are species in the cardiovirus genus of the picornaviridae family. for all cardioviruses, the viral polyprotein is initiated with a short leader (l) protein unique to this genus. the nuclear magnetic resonance (nmr) structure of le from encephalomyocarditis virus (emcv) has been determined. the protein has an nh2-proximal chcc zinc finger, a central linker, and a contiguous, highly acidic motif. the theiloviruses encode the same domains, with one or two ...201424335301
complete genome sequence of porcine encephalomyocarditis virus strain bd2.encephalomyocarditis virus (emcv) causes acute myocarditis in young pigs or reproductive failure in sows, and it is divided into two main groups. here, we report the complete genome sequence of emcv strain bd2, which belongs to group i.201324336370
an internal ribosome entry site (ires) mutant library for tuning expression level of multiple genes in mammalian cells.a set of mutated encephalomyocarditis virus (emcv) internal ribosome entry site (ires) elements with varying strengths is generated by mutating the translation initiation codons of 10(th), 11(th), and 12(th) aug to non-aug triplets. they are able to control the relative expression of multiple genes over a wide range in mammalian cells in both transient and stable transfections. the relative strength of each ires mutant remains similar in different mammalian cell lines and is not gene specific. t ...201324349195
human cell extract-derived cell-free systems for virus synthesis.cell-free synthesis of an infectious virus is an ideal tool for elucidating the mechanism of viral replication and for development of antiviral drugs. in this chapter, the synthesis of encephalomyocarditis virus (emcv) from rna and dna in a hela cell extract-derived in vitro protein expression system is described. when a synthetic emcv rna with a hammerhead ribozyme sequence at its 5'-end is incubated with a hela cell extract using a dialysis system, emcv particles are progressively synthesized. ...201424395414
a technique to increase protein yield in a rabbit reticulocyte lysate translation system.rabbit reticulocyte lysate (rrl) is a mammalian cell-free system for protein production. however, one of the limitations of this system is its low protein yield. inclusion of recombinant virus proteins and specific viral structures on target mrna could enhance protein production in rrl. here we show that simultaneous addition of influenza a virus ns1 protein and inclusion of the encephalomyocarditis virus (emcv) internal ribosome entry site (ires) in the target mrna facilitate translation initia ...201424447137
nmr elucidation of the role of mg2+ in the structure and stability of the conserved rna motifs of the emcv ires element.the three dimensional solution structures of a highly conserved 16mer rna, endowed with a classic 'gnra' tetraloop motif, and a 17mer rna containing a cytosine-rich heptaloop which is predicted to be a potential receptor for the former rna, of the i-domain of encephalomyocarditis virus ires have been determined by nmr spectroscopy. as mg(2+) plays an important role in the activity of the ires, the corresponding nmr structures of the mg(2+) bound rna complexes have also been determined. these rna ...201424448682
robustness of nanofiltration for increasing the viral safety margin of biological products.in this study, the virus-removal capacity of nanofiltration was assessed using validated laboratory scale models on a wide range of viruses (pseudorabies virus; human immunodeficiency virus; bovine viral diarrhea virus; west nile virus; hepatitis a virus; murine encephalomyocarditis virus; and porcine parvovirus) with sizes from 18 nm to 200 nm and applying the different process conditions existing in a number of grifols' plasma-derived manufacturing processes (thrombin, α1-proteinase inhibitor, ...201424485384
inactivated parapoxvirus ovis induces a transient increase in the expression of proinflammatory, th1-related, and autoregulatory cytokines in mice.the immunostimulatory properties of inactivated parapoxvirus ovis (ippvo) have long been investigated in different animal species and experimental settings. in this study, we investigated the effects of ippvo on cytokine expression in mice after intraperitoneal inoculation. spleen and sera collected from ippvo-treated mice at intervals after inoculation were submitted to cytokine mrna determination by real-time pcr (qpcr), serum protein concentration by elisa, and interferon (ifn)-α/β activity b ...201424519126
complete genome sequence of porcine encephalomyocarditis virus from an aardvark in china.a strain of encephalomyocarditis virus, hnxx13, was isolated from an aardvark in central china. the complete genome was sequenced and analyzed, and phylogenetic analysis suggests that hnxx13 belongs to encephalomyocarditis virus group 1.201424526627
indoleamine 2,3-dioxygenase 1 is upregulated in activated microglia in mice cerebellum during acute viral encephalitis.indoleamine 2,3-dioxygenase1 (ido1) is the rate-limiting enzyme in the kynurenine pathway that converts l-tryptophan to l-kynurenine. encephalomyocarditis virus (emcv) can cause acute myocarditis in various animals including mice. previously, ido1 has been reported to have an important immunomodulatory function in immune-related diseases. however, the pathophysiological roles of ido1 following acute viral infection of central nervous system are not fully understood. we observed that acute emcv i ...201424530381
identification of an lgp2-associated mda5 agonist in picornavirus-infected cells.the rig-i-like receptors rig-i, lgp2, and mda5 initiate an antiviral response that includes production of type i interferons (ifns). the nature of the rnas that trigger mda5 activation in infected cells remains unclear. here, we purify and characterise lgp2/rna complexes from cells infected with encephalomyocarditis virus (emcv), a picornavirus detected by mda5 and lgp2 but not rig-i. we show that those complexes contain rna that is highly enriched for mda5-stimulatory activity and for a specifi ...201424550253
cell-type-specific effects of rnase l on viral induction of beta interferon.the interferon (ifn)-inducible antiviral state is mediated in part by the 2',5'-oligoadenylate (2-5a) synthetase (oas)/rnase l system. 2-5a, produced from atp by oas proteins in response to viral double-stranded rna, binds to and activates rnase l. rnase l restricts viral infections by degrading viral and cellular rna, inducing autophagy and apoptosis, and producing rna degradation products that amplify production of type i interferons (ifns) through rig-i-like receptors. however, the effects of ...201424570368
the crystal structure of a cardiovirus rna-dependent rna polymerase reveals an unusual conformation of the polymerase active site.encephalomyocarditis virus (emcv) is a member of the cardiovirus genus within the large picornaviridae family, which includes a number of important human and animal pathogens. the rna-dependent rna polymerase (rdrp) 3dpol is a key enzyme for viral genome replication. in this study, we report the x-ray structures of two different crystal forms of the emcv rdrp determined at 2.8- and 2.15-å resolution. the in vitro elongation and vpg uridylylation activities of the purified enzyme have also been d ...201424600002
a new nanopcr molecular assay for detection of porcine bocavirus.nanoparticle-assisted polymerase chain reaction (nanopcr) is a novel method for the rapid amplification of dna and has been used for the detection of virus. for detection of porcine bocavirus (pbov), a sensitive and specific nanopcr assay was developed with a pair of primers that were designed based on ns1 gene sequences available in genbank. under the optimized conditions of the pbov nanopcr assay, the nanopcr assay was 100-fold more sensitive than a conventional pcr assay. the lower detection ...201424642242
construction of self-replicating subgenomic dengue virus 4 (denv4) replicon.dengue virus serotypes 1-4 are members of mosquito-borne flavivirus genus of flaviviridae family that encode one long open reading frame (orf) that is translated to a polyprotein. both host and virally encoded proteases function in the processing of the polyprotein by co-translational and posttranslational mechanisms to yield 10 mature proteins prior to viral rna replication. to study cis- and trans-acting factors involved in viral rna replication, many groups [1-8] have constructed cdnas encodi ...201424696335
comparative analysis of internal ribosomal entry sites as molecular tools for bicistronic expression.internal ribosomal entry sites (ireses) are sequences that drive cap-independent translation. they are found in some viral and cellular transcripts and they have been extensively used in both basic and applied research for the translation of two or more polypeptides from a single mrna molecule in eukaryotic cells. although the most widely used ires comes from the encephalomyocarditis virus (emcv), several other viral and cellular ires elements have been identified and successfully used, includin ...201424709397
the characteristics of synonymous codon usage in the initial and terminal translation regions of encephalomyocarditis virus.the synonymous codon usage patterns in the initial and terminal translation regions (itr, ttr) of the whole coding sequence of encephalomyocarditis virus (emcv) were analyzed in relation to those in its natural hosts using the sequences accessible in databases. in general, some low-usage host codons were found over-represented in the itr and ttr of the virus, while some high-usage host codons were found under-represented in the two viral regions. these relationships are thought to participate in ...201424720745
chemical derivatives of a small molecule deubiquitinase inhibitor have antiviral activity against several rna viruses.most antiviral treatment options target the invading pathogen and unavoidably encounter loss of efficacy as the pathogen mutates to overcome replication restrictions. a good strategy for circumventing drug resistance, or for pathogens without treatment options, is to target host cell proteins that are utilized by viruses during infection. the small molecule wp1130 is a selective deubiquitinase inhibitor shown previously to successfully reduce replication of noroviruses and some other rna viruses ...201424722666
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 ...201424722678
platelet-tlr7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis.viral infections have been associated with reduced platelet counts, the biological significance of which has remained elusive. here, we show that infection with encephalomyocarditis virus (emcv) rapidly reduces platelet count, and this response is attributed to platelet toll-like receptor 7 (tlr7). platelet-tlr7 stimulation mediates formation of large platelet-neutrophil aggregates, both in mouse and human blood. intriguingly, this process results in internalization of platelet cd41-fragments by ...201424755410
rapid detection of encephalomyocarditis virus by one-step reverse transcription loop-mediated isothermal amplification method.the encephalomyocarditis virus (emcv) can cause acute myocarditis in young pigs or reproductive failure in sows. in this study, a reverse transcription loop-mediated isothermal amplification (rt-lamp) assay was developed to detect emcv rna. the rt-lamp assay was highly sensitive and able to detect 2.2 × 10(-5)ng of emcv rna, as no cross-reaction was observed with other viruses. the rt-lamp assay was conducted in isothermal (62 °c) conditions within 50 min. the amplified products of emcv could be ...201424815878
development of a taqman-based real-time reverse transcription polymerase chain reaction assay for the detection of encephalomyocarditis virus.encephalomyocarditis virus (emcv) is one of the major zoonosis pathogens and can cause acute myocarditis in young pigs or reproductive failure in sows. in this study, a taqman-based real-time reverse transcription polymerase chain reaction (rt-pcr) assay targeting 3d gene of emcv was developed and their sensitivities and specificities were investigated. the results indicated that the standard curve had a wide dynamic range (10(1)-10(6) copies/μl) with a linear correlation (r(2)) of 0.996 between ...201424996131
phosphoproteomics combined with quantitative 14-3-3-affinity capture identifies sirt1 and rai as novel regulators of cytosolic double-stranded rna recognition pathway.viral double-stranded rna (dsrna) is the most important viral structure recognized by cytosolic pattern-recognition receptors of the innate immune system, and its recognition results in the activation of signaling cascades that stimulate the production of antiviral cytokines and apoptosis of infected cells. 14-3-3 proteins are ubiquitously expressed regulatory molecules that participate in a variety of cellular processes, and 14-3-3 protein-mediated signaling pathways are activated by cytoplasmi ...201424997996
amp-activated protein kinase phosphorylates emcv, tmev and safv leader proteins at different sites.cardioviruses of the encephalomyocarditis virus (emcv) and theilovirus species encode small, amino-terminal proteins called leaders (l). phosphorylation of the emcv l (le) at two distinct sites by ck2 and syk kinases is important for virus-induced nup phosphorylation and nucleocytoplasmic trafficking inhibition. despite similar biological activities, the le phosphorylation sites are not conserved in the theiloviruses, saffold virus (ls, safv) or theiler׳s murine encephalitis virus (lt, tmev) seq ...201424999048
trim13 is a negative regulator of mda5-mediated type i interferon production.retinoic acid-inducible gene i (rig-i) and melanoma differentiation-associated gene 5 (mda5) are essential intracellular detectors of viral rna. they contribute to the type i interferon (ifn) response that is crucial for host defense against viral infections. given the potent antiviral and proinflammatory activities elicited by the type i ifns, induction of the type i ifn response is tightly regulated. members of the tripartite motif (trim) family of proteins have recently emerged as key regulat ...201425008915
new small-molecule inhibitors effectively blocking picornavirus replication.few drugs targeting picornaviruses are available, making the discovery of antivirals a high priority. here, we identified and characterized three compounds from a library of kinase inhibitors that block replication of poliovirus, coxsackievirus b3, and encephalomyocarditis virus. using an in vitro translation-replication system, we showed that these drugs inhibit different stages of the poliovirus life cycle. a4(1) inhibited both the formation and functioning of the replication complexes, while ...201425008939
platelets: crossroads of immunity and hemostasis.in this issue of blood, koupenova and colleagues report that platelets express functional toll-like receptor 7 (tlr7) and contribute to host survival during viral infection. through a series of experiments utilizing mice deficient for tlr7 together with adoptive transfer of wild-type platelets, koupenova et al demonstrate that platelets specifically respond to viral analogs and intact virus, leading to platelet activation and binding to various leukocyte subsets. perhaps most importantly, this p ...201425082862
induction and suppression of innate antiviral responses by picornaviruses.the family picornaviridae comprises of small, non-enveloped, positive-strand rna viruses and contains many human and animal pathogens including enteroviruses (e.g. poliovirus, coxsackievirus, enterovirus 71 and rhinovirus), cardioviruses (e.g. encephalomyocarditis virus), hepatitis a virus and foot-and-mouth disease virus. picornavirus infections activate a cytosolic rna sensor, mda5, which in turn, induces a type i interferon response, a crucial component of antiviral immunity. moreover, picorn ...201425086453
evaluation of viral inactivation of pseudorabies virus, encephalomyocarditis virus, bovine viral diarrhea virus and porcine parvovirus in pancreatin of porcine origin.pancreatin is a substance containing enzymes, principally amylase, lipase, and protease. it is obtained from bovine or porcine pancreas and used in the treatment of pancreatic endocrine insufficiency in humans. regulations and safety concerns mandate viral clearance (virus removal or inactivation) in biopharmaceuticals such as pancreatin. a virus validation study was performed to evaluate virus clearance achieved in the final step of drying under vacuum by testing a panel of four animal viruses: ...201425110118
function of duck rig-i in induction of antiviral response against ibdv and avian influenza virus on chicken cells.the avian influenza (ai) h9n2 virus and ibdv are two major problems in the poultry industry. they have been prevalent among domestic poultry in asia for many years and have caused considerable economic losses. retinoic-acid-induced gene i (rig-i) is a cytoplasmic sensor of dsrna and ssrna. it can detect encephalomyocarditis virus (emcv) and vesicular stomatitis virus (vsv) in human cells, influenza virus in duck leads to production of ifn-β and ifn-stimulated antiviral genes and reductions in th ...201425128465
molecular basis for ebolavirus vp35 suppression of human dendritic cell maturation.zaire ebolavirus (ebov) vp35 is a double-stranded rna (dsrna)-binding protein that inhibits rig-i signaling and alpha/beta interferon (ifn-α/β) responses by both dsrna-binding-dependent and -independent mechanisms. vp35 also suppresses dendritic cell (dc) maturation. here, we define the pathways and mechanisms through which vp35 impairs dc maturation. wild-type vp35 (vp35-wt) and two well-characterized vp35 mutants (f239a and r322a) that independently ablate dsrna binding and rig-i inhibition we ...201425142601
nonstructural proteins 2c and 3d are involved in autophagy as induced by the encephalomyocarditis virus.encephalomyocarditis virus (emcv) can infect a variety of animal species and humans. although the emcv infection is known to induce autophagy to promote its replication in host cells, the viral proteins that are responsible for inducing autophagy are unknown.201425178311
binding interactions between the encephalomyocarditis virus leader and protein 2a.the leader (l) and 2a proteins of cardioviruses are the primary antihost agents produced during infection. for encephalomyocarditis virus (emcv), the prototype of the genus cardiovirus, these proteins interact independently with key cellular partners to bring about inhibition of active nucleocytoplasmic trafficking and cap-dependent translation, respectively. l and 2a also bind each other and require this cooperation to achieve their effects during infection. recombinant l and 2a interact with 1 ...201425210192
overlapping and distinct molecular determinants dictating the antiviral activities of trim56 against flaviviruses and coronavirus.the tripartite motif-containing (trim) proteins have emerged as a new class of host antiviral restriction factors, with several demonstrating roles in regulating innate antiviral responses. of >70 known trims, trim56 inhibits replication of bovine viral diarrhea virus, a ruminant pestivirus of the family flaviviridae, but has no appreciable effect on vesicular stomatitis virus (vsv), a rhabdovirus. yet the antiviral spectrum of trim56 remains undefined. in particular, how trim56 impacts human-pa ...201425253338
a translation system reconstituted with human factors proves that processing of encephalomyocarditis virus proteins 2a and 2b occurs in the elongation phase of translation without eukaryotic release factors.the genomic rna of encephalomyocarditis virus (emcv) encodes a single polyprotein, and the primary scission of the polyprotein occurs between nonstructural proteins 2a and 2b by an unknown mechanism. to gain insight into the mechanism of 2a-2b processing, we first translated the 2a-2b region in vitro with eukaryotic and prokaryotic translation systems. the 2a-2b processing occurred only in the eukaryotic systems, not in the prokaryotic systems, and the unprocessed 2a-2b protein synthesized by a ...201425258322
[isolation, identification and full-length genome sequence analysis of encephalomyocarditis virus from local aardvarks].encephalomyocarditis virus (emcv) is a natural epidemic zoonotic pathogen. however, no reports have been published regarding the isolation, identification and full-length genome of emcv from a local aardvark population. in present study, an emcv isolate hnxx13 was isolated from aardvarks named huainan-pig in henan province. the systematic identification, full-length genome sequencing and molecular characteristic analysis of the isolate hnxx13 were conducted. the result showed that the isolate wa ...201425272589
construction and characterization of an infectious cdna clone of encephalomyocarditis virus from pigs in china.encephalomyocarditis virus (emcv) infects animals of various species and causes a variety of clinical symptoms. in this study, an infectious full-length cdna clone was constructed, and the characteristics of the rescued virus were investigated in vitro and in vivo. our data demonstrated that the growth kinetics in vitro and plaque morphology of the rescued emcv rnj08 strain were similar to those of the parental strain. although rnj08 infected balb/c mice, none of the mice died during the observa ...201525430905
negative regulation of melanoma differentiation-associated gene 5 (mda5)-dependent antiviral innate immune responses by arf-like protein 5b.rig-i-like receptors (rlrs), including retinoic acid-inducible gene-i (rig-i) and mda5, constitute a family of cytoplasmic rna helicases that senses viral rna and mounts antiviral innate immunity by producing type i interferons and inflammatory cytokines. despite their essential roles in antiviral host defense, rlr signaling is negatively regulated to protect the host from excessive inflammation and autoimmunity. here, we identified adp-ribosylation factor-like protein 5b (arl5b), an arl family ...201525451939
response of host inflammasomes to viral infection.inflammasomes are multiprotein complexes that induce downstream immune responses to specific pathogens, environmental stimuli, and host cell damage. components of specific viruses activate different inflammasomes; for example, the influenza a virus m2 protein and encephalomyocarditis virus (emcv) 2b protein activate the nucleotide-binding oligomerization domain (nod)-like receptor family pyrin domain (pyd)-containing 3 (nlrp3) inflammasome, whereas viral double-stranded rna (dsrna) activates the ...201525456015
mgmt enrichment and second gene co-expression in hematopoietic progenitor cells using separate or dual-gene lentiviral vectors.the dna repair gene o(6)-methylguanine-dna methyltransferase (mgmt) allows efficient in vivo enrichment of transduced hematopoietic stem cells (hsc). thus, linking this selection strategy to therapeutic gene expression offers the potential to reconstitute diseased hematopoietic tissue with gene-corrected cells. however, different dual-gene expression vector strategies are limited by poor expression of one or both transgenes. to evaluate different co-expression strategies in the context of mgmt-m ...201525479595
isolation, molecular and phylogenetic analysis of encephalomyocarditis virus strain gs01 in china.encephalomyocarditis virus (emcv) is a small non-enveloped, single-stranded rna virus. it can infect many host species and cause acute myocarditis and respiratory failure in piglets, reproductive failure in pregnant sows. diseases caused by emcv currently affect the swine industry worldwide. in this study, an emcv strain was isolated from an aborted fetus in western china. it was identified by reverse-transcription polymerase chain reaction (rt-pcr) and genome sequencing. the subsequent results ...201525497352
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 ...201425531441
identification of vp1 peptides diagnostic of encephalomyocarditis virus from swine.encephalomyocarditis virus (emcv) can cause myocarditis, respiratory failure, reproductive failure, and sudden death in pre-weaned piglets, which has been isolated in china. emcv vp1 protein was one of the most important structural proteins and played an important role in the protective immunity. in this study, 10 monoclonal antibodies (mcabs) against emcv vp1 were screened and identified.201425547933
picornavirus rna polyadenylation by 3d(pol), the viral rna-dependent rna polymerase.poly(a) tails are functionally important features of all picornavirus rna genomes. some viruses have genomes with relatively short poly(a) tails (encephalomyocarditis virus) whereas others have genomes with longer poly(a) tails (polioviruses and rhinoviruses). here we review the polyadenylation of picornavirus rna as it relates to the structure and function of 3d(pol). poliovirus 3d(pol) uses template-dependent reiterative transcription mechanisms as it replicates the poly(a) tails of viral rna ...201525559071
tricistronic hepatitis c virus subgenomic replicon expressing double transgenes.to construct a tricistronic hepatitis c virus (hcv) replicon with double internal ribosome entry sites (ireses) of only 22 nucleotides for each, substituting the encephalomyocarditis virus (emcv) ireses, which are most often used as the translation initiation element to form hcv replicons.201425561795
stat2/irf9 directs a prolonged isgf3-like transcriptional response and antiviral activity in the absence of stat1.evidence is accumulating for the existence of a signal transducer and activator of transcription 2 (stat2)/interferon regulatory factor 9 (irf9)-dependent, stat1-independent interferon alpha (ifnα) signalling pathway. however, no detailed insight exists into the genome-wide transcriptional regulation and the biological implications of stat2/irf9-dependent ifnα signalling as compared with interferon-stimulated gene factor 3 (isgf3). in stat1-defeicient u3c cells stably overexpressing human stat2 ...025564224
translation initiation mediated by rna looping.eukaryotic translation initiation commences at the initiation codon near the 5' end of mrna by a 40s ribosomal subunit, and the recruitment of a 40s ribosome to an mrna is facilitated by translation initiation factors interacting with the m(7)g cap and/or poly(a) tail. the 40s ribosome recruited to an mrna is then transferred to the aug initiation codon with the help of translation initiation factors. to understand the mechanism by which the ribosome finds an initiation codon, we investigated th ...201525583496
cholesterol shuttling is important for rna replication of coxsackievirus b3 and encephalomyocarditis virus.picornaviruses are a family of positive-strand rna viruses that includes important human and animal pathogens. upon infection, picornaviruses induce an extensive remodelling of host cell membranes into replication organelles (ros), which is critical for replication. membrane lipids and lipid remodelling processes are at the base of ro formation, yet their involvement remains largely obscure. recently, phosphatidylinositol-4-phosphate was the first lipid discovered to be important for the replica ...201525645595
inactivation of viruses in platelet and plasma products using a riboflavin-and-uv-based photochemical treatment.multilayered blood safety programs reduce the risk of transfusion-transmitted diseases; however, there remains a risk of window period transmission of screened viruses and transmission of unscreened and emerging viruses from asymptomatic donors. to reduce this risk, a riboflavin-and-uv-light-based pathogen reduction process was evaluated against eight viral agents.201525731607
early microlesion of viral encephalitis confirmed by galectin-3 expression after a virus inoculation.galectin-3 is a β-galactosidase-binding lectin which is important in cell proliferation and apoptotic regulation. encephalomyocarditis virus (emcv), which includes the enterovirus genus, can cause not only acute myocarditis but also neuronal degeneration of central nervous system in various animals including mice. the pathophysiological role of galectin-3 in central nervous system following acute viral infection is not fully understood. the goal of this study is to determine the localization and ...201525736950
substance p receptor antagonism: a potential novel treatment option for viral-myocarditis.viral-myocarditis is an important cause of heart failure for which no specific treatment is available. we previously showed the neuropeptide substance p (sp) is associated with the pathogenesis of murine myocarditis caused by encephalomyocarditis virus (emcv). the current studies determined if pharmacological inhibition of sp-signaling via its high affinity receptor, nk1r and downstream g-protein, ras homolog gene family, member-a (rhoa), will be beneficial in viral-myocarditis. aprepitant (1.2  ...201525821814
rig-i-dependent antiviral immunity is effective against an rna virus encoding a potent suppressor of rnai.nodamura virus (nov) lethally infects suckling mice and contains a segmented positive-strand rna genome that encodes a potent suppressor of rna interference (rnai). recent studies have demonstrated immune detection and subsequent processing of nov dsrna replicative intermediates by the mouse rnai machinery. however, diverse rna viruses, including encephalomyocarditis virus that also triggers dicer-dependent biogenesis of viral sirnas in mouse cells, are targeted in mammals by rig-i-like receptor ...201525843799
inactivation of non-enveloped virus by 1,5 iodonaphthyl azide.a photoactive hydrophobic agent 1,5-iodonaphthyl-azide (ina), has been previously shown to completely inactivate the enveloped viruses. ina sequesters into the lipid bilayer of the virus envelope and upon uv-irradiation bind to the hydrophobic domains of the envelope glycoproteins. in our earlier study, we have shown that the venezuelan equine encephalitis virus (veev) genomic rna was also inactivated during the inactivation of the virus with ina.201525879201
serological prevalence of viral agents that induce reproductive failure in south korean wild boar.viral agents associated with reproductive failure such as aujeszky's disease virus (adv), encephalomyocarditis virus (emcv), and porcine parvovirus (ppv) have also been identified in european wild boar. to screen for the presence of antibodies against adv, emcv, and ppv from wild boar (sus scrofa) in south korea, 481 serum samples were collected from wild boar hunted between december 2010 and may 2011.201525888836
human cytokinome analysis for interferon response.cytokines are a group of small secreted proteins that mediate a diverse range of immune and nonimmune responses to inflammatory and microbial stimuli. only a few of these cytokines mount an antiviral response, including type i, ii, and iii interferons (ifns). during viral infections and under inflammatory conditions, a number of cytokines and chemokines are coproduced with ifn; however, no systematic study exists on the interactions of the cytokine repertoire with the ifn response. here, we perf ...201525926649
promotion of viral ires-mediated translation initiation under mild hypothermia.internal ribosome entry site (ires)-mediated translation is an essential replication step for certain viruses. as ires-mediated translation is regulated differently from cap-dependent translation under various cellular conditions, we sought to investigate whether temperature influences efficiency of viral ires-mediated translation initiation by using bicistronic reporter constructs containing an ires element of encephalomyocarditis virus (emcv), foot-and-mouth disease virus (fmdv), hepatitis c v ...201525951166
pathologic changes in the cardiac interstitium of mice infected with encephalomyocarditis virus.patients with myocarditis often develop dilated cardiomyopathy and congestive heart failure. histologically, myocarditis is manifested by rare foci of myocyte necrosis with interstitial inflammation, while cardiomyopathy is characterized by diffuse interstitial fibrosis, myocyte hypertrophy, and an absence of active interstitial inflammation. the relationship between myocardial inflammation and interstitial fibrosis is poorly understood. this relationship was examined in mice that developed a di ...201525990606
investigation of ires insertion into the genome of recombinant mva as a translation enhancer in the context of transcript decapping.recombinant modified vaccinia virus ankara (mva) has been used to deliver vaccine candidate antigens against infectious diseases and cancer. mva is a potent viral vector for inducing high magnitudes of antigen-specific cd8+ t cells; however the cellular immune responses to a recombinant antigen in mva could be further enhanced by increasing transgene expression. previous reports showed the importance of utilizing an early poxviral promoter for increasing transgene expression and therefore enhanc ...201526011541
an enterovirus-like rna construct for colon cancer suicide gene therapy.in gene therapy, the use of rna molecules as therapeutic agents has shown advantages over plasmid dna, including higher levels of safety. however, transient nature of rna has been a major obstacle in application of rna in gene therapy.201526025964
coxsackievirus b3 2a protease promotes encephalomyocarditis virus replication.to determine whether 2a protease of the enterovirus genus with type i internal ribosome entry site (ires) effect on the viral replication of type ii ires, coxsackievirus b3(cvb3)-encoded protease 2a and encephalomyocarditis virus (emcv) ires (type ii)-dependent or cap-dependent report gene were transiently co-expressed in eukaryotic cells. we found that cvb3 2a protease not only inhibited translation of cap-dependent reporter genes through the cleavage of eif4gi, but also conferred high emcv ire ...201526052084
the role of phosphodiesterase 12 (pde12) as a negative regulator of the innate immune response and the discovery of antiviral inhibitors.2',5'-oligoadenylate synthetase (oas) enzymes and rnase-l constitute a major effector arm of interferon (ifn)-mediated antiviral defense. oas produces a unique oligonucleotide second messenger, 2',5'-oligoadenylate (2-5a), that binds and activates rnase-l. this pathway is down-regulated by virus- and host-encoded enzymes that degrade 2-5a. phosphodiesterase 12 (pde12) was the first cellular 2-5a- degrading enzyme to be purified and described at a molecular level. inhibition of pde12 may up-regul ...201526055709
fatal encephalomyocarditis virus infection in an african savanna elephant (loxodonta africana) in a french zoo.a fatal case of encephalomyocarditis virus (emcv) involving an african elephant ( loxodonta africana ) occurred in november 2013 at the réserve africaine de sigean, france. an adult female was found dead without any preliminary symptoms. gross pathologic changes consisted of petechiae and hemorrhages on mucosae and internal organs, abundant transudate in the abdominal and pericardial cavities, and myocarditis. histopathologic examination showed extensive degeneration and necrosis of ventricular ...201526056902
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