Publications

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pilot longitudinal mosquito surveillance study in the danube delta biosphere reserve and the first reports of anopheles algeriensis theobald, 1903 and aedes hungaricus mihályi, 1955 for romania.mosquito-borne viruses (moboviruses) are of growing importance in many countries of europe. in romania and especially in the danube delta biosphere reserve (ddbr), mosquito and mobovirus surveillance are not performed on a regular basis. however, this type of study is crucially needed to evaluate the risk of pathogen transmission, to understand the ecology of emerging moboviruses, or to plan vector control programmes.201627066827
ecological characterization and molecular differentiation of culex pipiens complex taxa and culex torrentium in eastern austria.culex pipiens complex taxa differ in behaviour, ecophysiology and epidemiologic importance. despite their epidemiologic significance, information on genetic diversity, occurrence and seasonal and spatial distribution patterns of the cx. pipiens complex is still insufficient. assessment of seasonal and spatial distribution patterns of culex pipiens forms and their congener cx. torrentium is crucial for the understanding of their vector-pathogen dynamics.201627067139
high-throughput screening to enhance oncolytic virus immunotherapy.high-throughput screens can rapidly scan and capture large amounts of information across multiple biological parameters. although many screens have been designed to uncover potential new therapeutic targets capable of crippling viruses that cause disease, there have been relatively few directed at improving the efficacy of viruses that are used to treat disease. oncolytic viruses (ovs) are biotherapeutic agents with an inherent specificity for treating malignant disease. certain ov platforms - i ...201627579293
autophagy negatively regulates transmissible gastroenteritis virus replication.autophagy is an evolutionarily ancient pathway that has been shown to be important in the innate immune defense against several viruses. however, little is known about the regulatory role of autophagy in transmissible gastroenteritis virus (tgev) replication. in this study, we found that tgev infection increased the number of autophagosome-like double- and single-membrane vesicles in the cytoplasm of host cells, a phenomenon that is known to be related to autophagy. in addition, virus replicatio ...201627029407
high insecticides resistance in culex pipiens (diptera: culicidae) from tehran, capital of iran.during recent years transmission of dirofilaria immitis (dog heart worm) by culex pipiens and west nile virus have been reported from iran. the present study was preformed for evaluating the susceptibility status of cx. pipiens collected from capital city of tehran, iran.201628032100
amphotericin b inhibits enterovirus 71 replication by impeding viral entry.enterovirus 71 (ev71) infection causes hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children. there is thus an urgent need to find new treatments to control ev71 infection. in this study, we report potent inhibition of ev71 by a polyene antibiotic amphotericin b. amphotericin b profoundly diminished the expression of ev71 rna and viral proteins in the rd cells and the hek293 cells. as a result, ev71 production was inhibited by amphotericin b with an ...201627608771
m2bp inhibits hiv-1 virion production in a vimentin filaments-dependent manner.m2bp (also called 90k) is an interferon-stimulated gene product that is upregulated in hiv-1 infection. a recent study revealed that m2bp reduces the infectivity of hiv-1 by inhibiting the processing of the viral envelope protein. here we report that in addition to reducing viral infectivity, m2bp inhibits hiv-1 virion production. we provide evidence showing that m2bp inhibits hiv-1 gag trafficking to the plasma membrane in a vimentin-dependent manner. when vimentin filaments were collapsed by t ...201627604950
global profiling of the cellular alternative rna splicing landscape during virus-host interactions.alternative splicing (as) is a central mechanism of genetic regulation which modifies the sequence of rna transcripts in higher eukaryotes. as has been shown to increase both the variability and diversity of the cellular proteome by changing the composition of resulting proteins through differential choice of exons to be included in mature mrnas. in the present study, alterations to the global rna splicing landscape of cellular genes upon viral infection were investigated using mammalian reoviru ...201627598998
a simple and efficient in vivo non-viral rna transfection method for labeling the whole axonal tree of individual adult long-range projection neurons.we report a highly efficient, simple, and non-infective method for labeling individual long-range projection neurons (lrpns) in a specific location with enough sparseness and intensity to allow complete and unambiguous reconstructions of their entire axonal tree. the method is based on the "in vivo" transfection of a large rna construct that drives the massive expression of green fluorescent protein. the method combines two components: injection of a small volume of a hyperosmolar nacl solution ...201627047347
autophagy in plasma cell ontogeny and malignancy.autophagy is a highly conserved pathway that recycles cytosolic material and organelles via lysosomal degradation. once simplistically viewed as a non-selective survival strategy in dire straits, autophagy has emerged as a tightly regulated process ensuring organelle function, proteome plasticity, cell differentiation and tissue homeostasis, with key roles in physiology and disease. selective target recognition, mediated by specific adapter proteins, enables autophagy to orchestrate highly speci ...201626984755
endogenously-expressed nh2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands.the circumsporozoite protein is the most abundant polypeptide expressed by sporozoites, the malaria parasite stage capable of infecting humans. sporozoite invasion of mosquito salivary glands prior to transmission is likely mediated by a receptor/ligand-like interaction of the parasites with the target tissues, and the amino (nh2)-terminal portion of csp is involved in this interaction but not the tsr region on the carboxyl (c)-terminus. peptides based on the nh2-terminal domain could compete wi ...201626964736
filopodia and viruses: an analysis of membrane processes in entry mechanisms.filopodia are thin, actin rich bundles protruding from cell plasma membranes, serving physiological purposes, such as probing the environment and facilitating cell-to-cell adhesion. recent studies have highlighted that actively polymerized filopodial-protrusions are exploited during virus entry, trafficking, spread, and the development of clinical pathology of viral diseases. these observations have caused a surge in investigation of the key determinants of filopodial induction and their influen ...201627014223
pseudomonas aeruginosa activates pkc-alpha to invade middle ear epithelial cells.otitis media (om) is a group of complex inflammatory disorders affecting the middle ear which can be acute or chronic. chronic suppurative otitis media (csom) is a form of chronic om characterized by tympanic membrane perforation and discharge. despite the significant impact of csom on human population, it is still an understudied and unexplored research area. csom is a leading cause of hearing loss and life-threatening central nervous system complications. bacterial exposure especially pseudomo ...201626973629
genomic approaches for understanding dengue: insights from the virus, vector, and host.the incidence and geographic range of dengue have increased dramatically in recent decades. climate change, rapid urbanization and increased global travel have facilitated the spread of both efficient mosquito vectors and the four dengue virus serotypes between population centers. at the same time, significant advances in genomics approaches have provided insights into host-pathogen interactions, immunogenetics, and viral evolution in both humans and mosquitoes. here, we review these advances an ...201626931545
acyclic nucleoside phosphonates containing the amide bond.to study the influence of a linker rigidity and donor-acceptor properties, the p-ch2-o-chr- fragment in acyclic nucleoside phosphonates (e.g., acyclovir, tenofovir) was replaced by the p-ch2-hn-c(o)- residue. the respective phosphonates were synthesized in good yields by coupling the straight chain of ω-aminophosphonates and nucleobase-derived acetic acids with edc. based on the (1)h and (13)c nmr data, the unrestricted rotation within the methylene and 1,2-ethylidene linkers in phosphonates fro ...201627881885
isg12a restricts hepatitis c virus infection through the ubiquitination-dependent degradation pathway.interferons (ifns) restrict various kinds of viral infection via induction of hundreds of ifn-stimulated genes (isgs), while the functions of the majority of isgs are broadly unclear. here, we show that a high-ifn-inducible gene, isg12a (also known as ifi27), exhibits a nonapoptotic antiviral effect on hepatitis c virus (hcv) infection. viral ns5a protein is targeted specifically by isg12a, which mediates ns5a degradation via a ubiquitination-dependent proteasomal pathway. k374r mutation in ns5a ...201627194766
mechanisms of viral mutation.the remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. rates of spontaneous mutation vary amply among viruses. rna viruses mutate faster than dna viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. viral mutation rates are modulated at different levels, including polymerase fidelity, sequence ...201627392606
distal-less induces elemental color patterns in junonia butterfly wings.the border ocellus, or eyespot, is a conspicuous color pattern element in butterfly wings. for two decades, it has been hypothesized that transcription factors such as distal-less (dll) are responsible for eyespot pattern development in butterfly wings, based on their expression in the prospective eyespots. in particular, it has been suggested that dll is a determinant for eyespot size. however, functional evidence for this hypothesis has remained incomplete, due to technical difficulties.201626937287
small rna profiling in dengue virus 2-infected aedes mosquito cells reveals viral pirnas and novel host mirnas.in aedes mosquitoes, infections with arthropod-borne viruses (arboviruses) trigger or modulate the expression of various classes of viral and host-derived small rnas, including small interfering rnas (sirnas), piwi interacting rnas (pirnas), and micrornas (mirnas). viral sirnas are at the core of the antiviral rna interference machinery, one of the key pathways that limit virus replication in invertebrates. besides sirnas, aedes mosquitoes and cells derived from these insects produce arbovirus-d ...201626914027
excess cerebral tnf causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-tnf agents.the basic mechanism of the major neurodegenerative diseases, including neurogenic pain, needs to be agreed upon before rational treatments can be determined, but this knowledge is still in a state of flux. most have agreed for decades that these disease states, both infectious and non-infectious, share arguments incriminating excitotoxicity induced by excessive extracellular cerebral glutamate. excess cerebral levels of tumor necrosis factor (tnf) are also documented in the same group of disease ...201627596607
trim14 inhibits hepatitis c virus infection by spry domain-dependent targeted degradation of the viral ns5a protein.tripartite motif 14 (trim14) was reported to function as a mitochondrial signaling adaptor in mediating innate immune responses. however, the involvement of trim14 in host defense against viral infection and molecular mechanisms remain unclear. here, we demonstrated that enforced expression of trim14 could potently inhibit the infection and replication of hcv in hepatocytes, whereas trim14 knockout cells became more susceptible to hcv infection. interestingly, further experiments revealed that s ...201627578425
interferon-inducible protein scotin interferes with hcv replication through the autolysosomal degradation of ns5a.hepatitis c virus (hcv) utilizes autophagy to promote its propagation. here we show the autophagy-mediated suppression of hcv replication via the endoplasmic reticulum (er) protein scotin. scotin overexpression inhibits hcv replication and infectious virion production in cells infected with cell culture-derived hcv. hcv nonstructural 5a (ns5a) protein, which is a critical factor for hcv rna replication, interacts with the ifn-β-inducible protein scotin, which transports ns5a to autophagosomes fo ...201626868272
transstadial effects of bti on traits of aedes aegypti and infection with dengue virus.most mosquito control efforts are primarily focused on reducing the adult population size mediated by reductions in the larval population, which should lower risk of disease transmission. although the aim of larviciding is to reduce larval abundance and thus recruitment of adults, nonlethal effects on adults are possible, including transstadial effects on phenotypes of adults such as survival and pathogen infection and transmission. in addition, the mortality induced by control efforts may act i ...201626871951
identification of a nucleotide in 5' untranslated region contributing to virus replication and virulence of coxsackievirus a16.coxsackievirus a16 (ca16) and enterovirus 71 (ev71) are two main causative pathogens of hand, foot and mouth disease (hfmd). unlike ev71, virulence determinants of ca16, particularly within 5' untranslated region (5'utr), have not been investigated until now. here, a series of nucleotides present in 5'utr of lethal but not in non-lethal ca16 strains were screened by aligning nucleotide sequences of lethal circulating changchun ca16 and the prototype g10 as well as non-lethal shzh05 strains. a re ...201626861413
activation of rnase l is dependent on oas3 expression during infection with diverse human viruses.the 2',5'-oligoadenylate (2-5a) synthetase (oas)-rnase l system is an ifn-induced antiviral pathway. rnase l activity depends on 2-5a, synthesized by oas. although all three enzymatically active oas proteins in humans--oas1, oas2, and oas3--synthesize 2-5a upon binding dsrna, it is unclear which are responsible for rnase l activation during viral infection. we used clustered regularly interspaced short palindromic repeats (crispr)-crispr-associated protein-9 nuclease (cas9) technology to enginee ...201626858407
big data offers novel insights for oncolytic virus immunotherapy.large-scale assays, such as microarrays, next-generation sequencing and various "omics" technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (ovit) in the cancer setting. tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and function ...201626861383
inhibition of chikungunya virus replication by 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea(mbzm-n-ibt).chikungunya virus (chikv) infection is one of the most challenging human arboviral infections with global significance and without any specific antiviral. in this investigation, 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (mbzm-n-ibt) was synthesised as a molecular hybrid of 2-methyl benzimidazole and isatin-β-thiosemicarbazone and its anti-chikv property was evaluated. the release of infectious virus particles was calculated by plaque assay, expression profil ...201626843462
human papillomavirus e2 regulates srsf3 (srp20) to promote capsid protein expression in infected differentiated keratinocytes.the human papillomavirus (hpv) life cycle is tightly linked to differentiation of the infected epithelial cell, suggesting a sophisticated interplay between host cell metabolism and virus replication. previously, we demonstrated in differentiated keratinocytes in vitro and in vivo that hpv type 16 (hpv16) infection caused increased levels of the cellular sr splicing factors (srsfs) srsf1 (asf/sf2), srsf2 (sc35), and srsf3 (srp20). moreover, the viral e2 transcription and replication factor that ...201626962216
down-regulation of p21-activated serine/threonine kinase 1 is involved in loss of mesencephalic dopamine neurons.although the roles of p21-activated serine/threonine kinase 1 (pak1) have been reported in some neurodegenerative diseases, details regarding neurodegeneration are still limited. hence, we tried to determine the role of pak1 and molecular mechanisms of neuronal death involved in neurodegeneration.201627121078
working with zika and usutu viruses in vitro.usutu (usuv) and zika (zikv) viruses are emerging arboviruses of significant medical and veterinary importance. these viruses have not been studied as well as other medically important arboviruses such as west nile (wnv), dengue (denv), or chikungunya (chikv) viruses. as such, information regarding the behavior of zikv and usuv viruses in the laboratory is dated. usutu virus re-emerged in austria in 2001 and has since spread throughout the european and asian continents causing significant mortal ...201627541001
seropositivity for west nile virus antibodies in patients affected by myasthenia gravis.myasthenia gravis (mg) is an autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal muscles. specific auto-antibodies against acetylcholine receptor (achr) are present in the majority of mg patients, although the main cause behind its development still remains unclear. recently mg development following west nile virus (wnv) infection has been described in patients without any earlier evidence of mg. it is known that infectious agents trigger immune response ...201626858791
apoptosis, autophagy and unfolded protein response pathways in arbovirus replication and pathogenesis.arboviruses are pathogens that widely affect the health of people in different communities around the world. recently, a few successful approaches toward production of effective vaccines against some of these pathogens have been developed, but treatment and prevention of the resulting diseases remain a major health and research concern. the arbovirus infection and replication processes are complex, and many factors are involved in their regulation. apoptosis, autophagy and the unfolded protein r ...201626781343
a de novo transcriptome analysis shows that modulation of the jak-stat signaling pathway by salmonid alphavirus subtype 3 favors virus replication in macrophage/dendritic-like to-cells.the janus kinase (jak) and signaling transducer activator of transcription (stat) pathway mediates the signaling of genes required for cellular development and homeostasis. to elucidate the effect of type i ifn on the jak/stat pathway in salmonid alphavirus subtype 3 (sav3) infected macrophage/dendritic like to-cells derived from atlantic salmon (salmo salar l) headkidney leukocytes, we used a differential transcriptome analysis by rna-seq and the kyoto encyclopedia of genes and genomes (keggs) ...201627215196
isg15 deficiency and increased viral resistance in humans but not mice.isg15 is an interferon (ifn)-α/β-induced ubiquitin-like protein. it exists as a free molecule, intracellularly and extracellularly, and conjugated to target proteins. studies in mice have demonstrated a role for isg15 in antiviral immunity. by contrast, human isg15 was shown to have critical immune functions, but not in antiviral immunity. namely, free extracellular isg15 is crucial in ifn-γ-dependent antimycobacterial immunity, while free intracellular isg15 is crucial for usp18-mediated downre ...201627193971
mutagenesis of coronavirus nsp14 reveals its potential role in modulation of the innate immune response.coronavirus (cov) nonstructural protein 14 (nsp14) is a 60-kda protein encoded by the replicase gene that is part of the replication-transcription complex. it is a bifunctional enzyme bearing 3'-to-5' exoribonuclease (exon) and guanine-n7-methyltransferase (n7-mtase) activities. exon hydrolyzes single-stranded rnas and double-stranded rnas (dsrnas) and is part of a proofreading system responsible for the high fidelity of cov replication. nsp14 n7-mtase activity is required for viral mrna cap syn ...201627009949
a viral mrna motif at the 3'-untranslated region that confers translatability in a cell-specific manner. implications for virus evolution.sindbis virus (sinv) mrnas contain several motifs that participate in the regulation of their translation. we have discovered a motif at the 3' untranslated region (utr) of viral mrnas, constituted by three repeated sequences, which is involved in the translation of both sinv genomic and subgenomic mrnas in insect, but not in mammalian cells. these data illustrate for the first time that an element present at the 3'-utr confers translatability to mrnas from an animal virus in a cell-specific man ...201626755446
functional translational readthrough: a systems biology perspective.translational readthrough (tr) has come into renewed focus because systems biology approaches have identified the first human genes undergoing functional translational readthrough (ftr). ftr creates functional extensions to proteins by continuing translation of the mrna downstream of the stop codon. here we review recent developments in tr research with a focus on the identification of ftr in humans and the systems biology methods that have spurred these discoveries.201627490485
cytoplasmic drosha activity generated by alternative splicing.rnase iii enzyme drosha interacts with dgcr8 to form the microprocessor, initiating canonical microrna (mirna) maturation in the nucleus. here, we re-evaluated where drosha functions in cells using drosha and/or dgcr8 knock out (ko) cells and cleavage reporters. interestingly, a truncated drosha mutant located exclusively in the cytoplasm cleaved pri-mirna effectively in a dgcr8-dependent manner. in addition, we demonstrated that in vitro generated pri-mirnas when transfected into cells could be ...201627471035
activation of the dna damage response by rna viruses.rna viruses are a genetically diverse group of pathogens that are responsible for some of the most prevalent and lethal human diseases. numerous viruses introduce dna damage and genetic instability in host cells during their lifecycles and some species also manipulate components of the dna damage response (ddr), a complex and sophisticated series of cellular pathways that have evolved to detect and repair dna lesions. activation and manipulation of the ddr by dna viruses has been extensively stu ...201626751489
characterization of ryden (c19orf66) as an interferon-stimulated cellular inhibitor against dengue virus replication.dengue virus (denv) is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. however, no vaccine or specific antiviral is available for dengue. as seen in other rna viruses, the innate immune system plays a key role in controlling denv infection and disease outcome. although the interferon (ifn) response, which is central to host protective immunity, has been reported to limit denv replication, the molecular details of how denv infection is modulated ...201626735137
seroprevalence and risk factors of inkoo virus in northern sweden.the mosquito-borne inkoo virus (inkv) is a member of the california serogroup in the family bunyaviridae, genus orthobunyavirus these viruses are associated with fever and encephalitis, although inkv infections are not usually reported and the incidence is largely unknown. the aim of the study was to determine the prevalence of anti-inkv antibodies and associated risk factors in humans living in northern sweden. seroprevalence was investigated using the world health organization monitoring of tr ...201626928830
receptor-targeted nipah virus glycoproteins improve cell-type selective gene delivery and reveal a preference for membrane-proximal cell attachment.receptor-targeted lentiviral vectors (lvs) can be an effective tool for selective transfer of genes into distinct cell types of choice. moreover, they can be used to determine the molecular properties that cell surface proteins must fulfill to act as receptors for viral glycoproteins. here we show that lvs pseudotyped with receptor-targeted nipah virus (niv) glycoproteins effectively enter into cells when they use cell surface proteins as receptors that bring them closely enough to the cell memb ...201627281338
a new defective helper rna to produce recombinant sindbis virus that infects neurons but does not propagate.recombinant sindbis viruses are important tools in neuroscience because they combine rapid and high transgene expression with a capacity to carry large transgenes. currently, two packaging systems based on the defective helper (dh) rnas dh(26s)5'sin and dh-bb(trna;te12) are available for generating recombinant sindbis virus that is neurotropic (able to infect neurons and potentially other cells). both systems produce a fraction of viral particles that can propagate beyond the primary infected ne ...201627252627
hepatitis c virus infection induces autophagy as a prosurvival mechanism to alleviate hepatic er-stress response.hepatitis c virus (hcv) infection frequently leads to chronic liver disease, liver cirrhosis and hepatocellular carcinoma (hcc). the molecular mechanisms by which hcv infection leads to chronic liver disease and hcc are not well understood. the infection cycle of hcv is initiated by the attachment and entry of virus particles into a hepatocyte. replication of the hcv genome inside hepatocytes leads to accumulation of large amounts of viral proteins and rna replication intermediates in the endopl ...201627223299
analysis of the contribution of hemocytes and autophagy to drosophila antiviral immunity.antiviral immunity in the model organism drosophila melanogaster involves the broadly active intrinsic mechanism of rna interference (rnai) and virus-specific inducible responses. here, using a panel of six viruses, we investigated the role of hemocytes and autophagy in the control of viral infections. injection of latex beads to saturate phagocytosis, or genetic depletion of hemocytes, resulted in decreased survival and increased viral titers following infection with cricket paralysis virus (cr ...201627009948
lncrna oip5-as1/cyrano sponges rna-binding protein hur.the function of the vast majority of mammalian long noncoding (lnc) rnas remains unknown. here, analysis of a highly abundant mammalian lncrna, oip5-as1, known as cyrano in zebrafish, revealed that oip5-as1 reduces cell proliferation. in human cervical carcinoma hela cells, the rna-binding protein hur, which enhances cell proliferation, associated with oip5-as1 and stabilized it. tagging oip5-as1 with ms2 hairpins to identify associated micrornas revealed that mir-424 interacted with oip5-as1 an ...201626819413
lv305, a dendritic cell-targeting integration-deficient zvex(tm)-based lentiviral vector encoding ny-eso-1, induces potent anti-tumor immune response.we have engineered an integration-deficient lentiviral vector, lv305, to deliver the tumor antigen ny-eso-1 to human dendritic cells in vivo through pseudotyping with a modified sindbis virus envelop protein. mice immunized once with lv305 developed strong, dose-dependent, multifunctional, and cytotoxic ny-eso-1-specific cluster of differentiation 8 (cd8) t cells within 14 days post-immunization and could be boosted with lv305 at least twice to recall peak-level cd8 t-cell responses. immunizatio ...201627626061
middle east respiratory syndrome coronavirus ns4b protein inhibits host rnase l activation.middle east respiratory syndrome coronavirus (mers-cov) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (sars-cov) in 2002. like many coronaviruses, mers-cov carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. evasion of host innate immunity through interferon (ifn) antagonism is a critical component of viral pathogenesis. the ifn-inducible ...201627025250
capturing and concentrating adenovirus using magnetic anionic nanobeads.we recently demonstrated how various enveloped viruses can be efficiently concentrated using magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic anhydrate). however, the exact mechanism of interaction between the virus particles and anionic beads remains unclear. to further investigate whether these magnetic anionic beads specifically bind to the viral envelope, we examined their potential interaction with a nonenveloped virus (adenovirus). the beads were incubated with ...201627274228
widespread 3'-end uridylation in eukaryotic rna viruses.rna 3' uridylation occurs pervasively in eukaryotes, but is poorly characterized in viruses. in this study, we demonstrate that a broad array of rna viruses, including mycoviruses, plant viruses and animal viruses, possess a novel population of rna species bearing nontemplated oligo(u) or (u)-rich tails, suggesting widespread 3' uridylation in eukaryotic viruses. given the biological relevance of 3' uridylation to eukaryotic rna degradation, we propose a conserved but as-yet-unknown mechanism in ...201627151171
the role of phlebovirus glycoproteins in viral entry, assembly and release.bunyaviruses are enveloped viruses with a tripartite rna genome that can pose a serious threat to animal and human health. members of the phlebovirus genus of the family bunyaviridae are transmitted by mosquitos and ticks to humans and include highly pathogenic agents like rift valley fever virus (rvfv) and severe fever with thrombocytopenia syndrome virus (sftsv) as well as viruses that do not cause disease in humans, like uukuniemi virus (uukv). phleboviruses and other bunyaviruses use their e ...201627455305
exaptive origins of regulated mrna decay in eukaryotes.eukaryotic gene expression is extensively controlled at the level of mrna stability and the mechanisms underlying this regulation are markedly different from their archaeal and bacterial counterparts. we propose that two such mechanisms, nonsense-mediated decay (nmd) and motif-specific transcript destabilization by ccch-type zinc finger rna-binding proteins, originated as a part of cellular defense against rna pathogens. these branches of the mrna turnover pathway might have been used by primeva ...201627438915
n-terminal domain of feline calicivirus (fcv) proteinase-polymerase contributes to the inhibition of host cell transcription.feline calicivirus (fcv) infection results in the inhibition of host protein synthesis, known as "shut-off". however, the precise mechanism of shut-off remains unknown. here, we found that the fcv strain 2280 proteinase-polymerase (pp) protein can suppress luciferase reporter gene expression driven by endogenous and exogenous promoters. furthermore, we found that the n-terminal 263 aa of pp (ppn-263) determined its shut-off activity using the expression of truncated proteins. however, the same d ...201627447663
gain-of-function mutations in protein kinase cα (pkcα) may promote synaptic defects in alzheimer's disease.alzheimer's disease (ad) is a progressive dementia disorder characterized by synaptic degeneration and amyloid-β (aβ) accumulation in the brain. through whole-genome sequencing of 1345 individuals from 410 families with late-onset ad (load), we identified three highly penetrant variants in prkca, the gene that encodes protein kinase cα (pkcα), in five of the families. all three variants linked with load displayed increased catalytic activity relative to wild-type pkcα as assessed in live-cell im ...201627165780
presynaptic serotonin 2a receptors modulate thalamocortical plasticity and associative learning.higher-level cognitive processes strongly depend on a complex interplay between mediodorsal thalamus nuclei and the prefrontal cortex (pfc). alteration of thalamofrontal connectivity has been involved in cognitive deficits of schizophrenia. prefrontal serotonin (5-ht)2a receptors play an essential role in cortical network activity, but the mechanism underlying their modulation of glutamatergic transmission and plasticity at thalamocortical synapses remains largely unexplored. here, we show that ...201626903620
design of a titering assay for lentiviral vectors utilizing direct extraction of dna from transduced cells in microtiter plates.using lentiviral vector products in clinical applications requires an accurate method for measuring transduction titer. for vectors lacking a marker gene, quantitative polymerase chain reaction is used to evaluate the number of vector dna copies in transduced target cells, from which a transduction titer is calculated. immune design previously described an integration-deficient lentiviral vector pseudotyped with a modified sindbis virus envelope for use in cancer immunotherapy (vp02, of the zvex ...201626942209
hippocampal dendritic spines are segregated depending on their actin polymerization.dendritic spines are mushroom-shaped protrusions of the postsynaptic membrane. spines receive the majority of glutamatergic synaptic inputs. their morphology, dynamics, and density have been related to synaptic plasticity and learning. the main determinant of spine shape is filamentous actin. using frap, we have reexamined the actin dynamics of individual spines from pyramidal hippocampal neurons, both in cultures and in hippocampal organotypic slices. our results indicate that, in cultures, the ...201626881098
cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances.oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized phase iii clinical trial hurdle. both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. there is increasing interest in their combination with cytotoxic agents, radiotherapy and i ...201627579292
emergence of a large-plaque variant in mice infected with coxsackievirus b3.coxsackieviruses are enteric viruses that frequently infect humans. to examine coxsackievirus pathogenesis, we orally inoculated mice with the coxsackievirus b3 (cvb3) nancy strain. using hela cell plaque assays with agar overlays, we noticed that some fecal viruses generated plaques >100 times as large as inoculum viruses. these large-plaque variants emerged following viral replication in several different tissues. we identified a single amino acid change, n63y, in the vp3 capsid protein that w ...201627025249
an mrna-specific trnai carrier eif2a plays a pivotal role in cell proliferation under stress conditions: stress-resistant translation of c-src mrna is mediated by eif2a.c-src, a non-receptor protein tyrosine kinase, activates nf-κb and stat3, which in turn triggers the transcription of anti-apoptosis- and cell cycle-related genes. c-src protein regulates cell proliferation, cell motility and programmed cell death. and the elevated level of activated c-src protein is related with solid tumor generation. translation of c-src mrna is directed by an ires element which mediates persistent translation under stress conditions when translation of most mrnas is inhibite ...201627899592
health technology assessment of pathogen reduction technologies applied to plasma for clinical use.although existing clinical evidence shows that the transfusion of blood components is becoming increasingly safe, the risk of transmission of known and unknown pathogens, new pathogens or re-emerging pathogens still persists. pathogen reduction technologies may offer a new approach to increase blood safety. the study is the output of collaboration between the italian national blood centre and the post-graduate school of health economics and management, catholic university of the sacred heart, ro ...201627403740
antimicrobial action of compounds from marine seaweed.seaweed produces metabolites aiding in the protection against different environmental stresses. these compounds show antiviral, antiprotozoal, antifungal, and antibacterial properties. macroalgae can be cultured in high volumes and would represent an attractive source of potential compounds useful for unconventional drugs able to control new diseases or multiresistant strains of pathogenic microorganisms. the substances isolated from green, brown and red algae showing potent antimicrobial activi ...201627005637
ribosomal frameshifting and transcriptional slippage: from genetic steganography and cryptography to adventitious use.genetic decoding is not 'frozen' as was earlier thought, but dynamic. one facet of this is frameshifting that often results in synthesis of a c-terminal region encoded by a new frame. ribosomal frameshifting is utilized for the synthesis of additional products, for regulatory purposes and for translational 'correction' of problem or 'savior' indels. utilization for synthesis of additional products occurs prominently in the decoding of mobile chromosomal element and viral genomes. one class of re ...201627436286
host-feeding patterns of mosquito species in germany.mosquito-borne pathogens are of growing importance in many countries of europe including germany. at the same time, the transmission cycles of most mosquito-borne pathogens (e.g. viruses or filarial parasites) are not completely understood. there is especially a lack of knowledge about the vector capacity of the different mosquito species, which is strongly influenced by their host-feeding patterns. while this kind of information is important to identify the relevant vector species, e.g. to dire ...201627259984
outrunning the red queen: bystander activation as a means of outpacing innate immune subversion by intracellular pathogens.originally described by the late evolutionary biologist leigh van valen, the red queen hypothesis posits that the evolutionary arms race between hosts and their pathogens selects for discrete, genetically encoded events that lead to competitive advantages over the other species. examples of immune evasion strategies are seen throughout the co-evolution of the mammalian immune system and pathogens, such as the enzymatic inactivation of nuclear factor-κb signaling or host translation by pathogen-e ...201627545071
tick infestation in birds and prevalence of pathogens in ticks collected from different places in germany.the importance of ticks and tick-borne pathogens for human and animal health has been increasing over the past decades. for their transportation and dissemination, birds may play a more important role than wingless hosts. in this study, tick infestation of birds in germany was examined. eight hundred ninety-two captured birds were infested with ticks and belonged to 48 different species, of which blackbirds (turdus merula) and song thrushes (turdus philomelos) were most strongly infested. ground ...201627048511
replicon rna viral vectors as vaccines.single-stranded rna viruses of both positive and negative polarity have been used as vectors for vaccine development. in this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. administration of replicon rna vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. immunization of mice, chicken, pigs and primates with virus-like particles, naked r ...201627827980
actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in drosophila melanogaster.damage-associated molecular patterns (damps) are molecules released by dead cells that trigger sterile inflammation and, in vertebrates, adaptive immunity. actin is a damp detected in mammals by the receptor, dngr-1, expressed by dendritic cells (dcs). dngr-1 is phosphorylated by src-family kinases and recruits the tyrosine kinase syk to promote dc cross-presentation of dead cell-associated antigens. here we report that actin is also a damp in invertebrates that lack dcs and adaptive immunity. a ...201627871362
mosquito-transmitted viruses - the great brazilian challenge.arboviruses pose a serious threat to public health worldwide, overloading the healthcare system and causing economic losses. these viruses form a very diverse group, and in brazil, arboviruses belonging to the families flaviviridae and togaviridae are predominant. unfortunately, the number of arboviruses increases in proportion with factors such as deforestation, poor sanitation, climate changes, and introduction of new viruses like chikungunya virus and zika virus. in brazil, dengue is endemic, ...201627818091
molecular detection of flaviviruses and alphaviruses in mosquitoes (diptera: culicidae) from coastal ecosystems in the colombian caribbean.arboviruses belonging to the genera flavivirus and alphavirus were detected in mosquitoes in a rural area of san bernardo del viento (córdoba, colombia). a total of 22,180 mosquitoes were collected, sorted into 2,102 pools, and tested by generic/nested reverse transcription-polymerase chain reaction. venezuelan equine encephalitis virus, dengue virus, west nile virus, st. louis encephalitis virus, yellow fever virus, and culex flavivirus were detected and identified by sequencing. the detection ...201627706377
a field-deployable reverse transcription recombinase polymerase amplification assay for rapid detection of the chikungunya virus.chikungunya virus (chikv) is a mosquito-borne virus currently transmitted in about 60 countries. chikv causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. detection of the infection is mostly done using rt-rcr or elisa, which are not suitable for point-of-care diagnosis.201627685649
the viral capping enzyme nsp1: a novel target for the inhibition of chikungunya virus infection.the chikungunya virus (chikv) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. we discovered a novel class of small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6h)-ones) with potent in vitro activity against chikv isolates from different geographical regions. drug-resistant variants were selected and these carried a p34s substitution in non-structural protein 1 (nsp1), the main enzyme involve ...201627545976
alphavirus infection: host cell shut-off and inhibition of antiviral responses.alphaviruses cause debilitating disease in humans and animals and are transmitted by blood-feeding arthropods, typically mosquitoes. with a traditional focus on two models, sindbis virus and semliki forest virus, alphavirus research has significantly intensified in the last decade partly due to the re-emergence and dramatic expansion of chikungunya virus in asia, europe, and the americas. as a consequence, alphavirus-host interactions are now understood in much more molecular detail, and importa ...201627294951
effects of an in-frame deletion of the 6k gene locus from the genome of ross river virus.the alphaviral6kgene region encodes the two structural proteins 6k protein and, due to a ribosomal frameshift event, the transframe protein (tf). here, we characterized the role of the6kproteins in the arthritogenic alphavirus ross river virus (rrv) in infected cells and in mice, using a novel6kin-frame deletion mutant. comprehensive microscopic analysis revealed that the6kproteins were predominantly localized at the endoplasmic reticulum of rrv-infected cells. rrv virions that lack the6kprotein ...201626865723
surveillance for western equine encephalitis, st. louis encephalitis, and west nile viruses using reverse transcription loop-mediated isothermal amplification.collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. vector control districts in california routinely monitor for three human pathogenic viruses including west nile virus (wnv), western equine encephalitis virus (weev), and st. louis encephalitis virus (slev). reverse transcription quantitative polymerase chain reaction ...201626807734
emerging role of lipid droplets in aedes aegypti immune response against bacteria and dengue virus.in mammals, lipid droplets (lds) are ubiquitous organelles that modulate immune and inflammatory responses through the production of lipid mediators. in insects, it is unknown whether lds play any role during the development of immune responses. we show that aedes aegypti aag2 cells - an immune responsive cell lineage - accumulates lds when challenged with enterobacter cloacae, sindbis, and dengue viruses. microarray analysis of aag2 challenged with e.cloacae or infected with dengue virus reveal ...201626887863
a quantitative real-time rt-pcr assay for the detection of venezuelan equine encephalitis virus utilizing a universal alphavirus control rna.venezuelan equine encephalitis virus (veev) is an alphavirus from the family togaviridae that causes epizootic outbreaks in equids and humans in central and south america. so far, most studies use conventional reverse transcriptase pcr assays for the detection of the different veev subtypes. here we describe the development of a taqman quantitative real-time reverse transcriptase pcr assay for the specific detection and quantitation of all veev subtypes which uses in parallel a universal equine ...201628042576
ancient recombination events and the origins of hepatitis e virus.hepatitis e virus (hev) is an enteric, single-stranded, positive sense rna virus and a significant etiological agent of hepatitis, causing sporadic infections and outbreaks globally. tracing the evolutionary ancestry of hev has proved difficult since its identification in 1992, it has been reclassified several times, and confusion remains surrounding its origins and ancestry.201627733122
cytokine diedel and a viral homologue suppress the imd pathway in drosophila.viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. for example, many vertebrate dna viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. insect viruses express suppressors of rna interference or apoptosis, highlighting the importance of these cell intrins ...201626739560
serosurveillance of viral pathogens circulating in west africa.sub-saharan africa is home to a variety of pathogens, but disease surveillance and the healthcare infrastructure necessary for proper management and control are severely limited. lassa virus, the cause of lassa fever, a severe hemorrhagic fever in humans is endemic in west africa. in sierra leone at the kenema government hospital lassa diagnostic laboratory, up to 70 % of acute patient samples suspected of lassa fever test negative for lassa virus infection. this large amount of acute undiagnose ...201627716429
temporal variation in sindbis virus antibody prevalence in bird hosts in an endemic area in sweden.sindbis virus (sinv) is a mosquito-borne bird virus that occasionally causes human disease in fennoscandia, suggested to have cyclic 7-year intervals between outbreaks. reliable data on human infections in sweden is however lacking. here we investigated the sinv antibody prevalence among birds in a swedish area endemic to sinv to scrutinize if a cyclic variation in antibody prevalence is present in the natural host of sinv. serum from birds were sampled in the summers of 2002-2004 and 2009 in th ...201627579607
neurological sequelae resulting from encephalitic alphavirus infection.the recent surge in viral clinical cases and associated neurological deficits have reminded us that viral infections can lead to detrimental, long-term effects, termed sequelae, in survivors. alphaviruses are enveloped, single-stranded positive-sense rna viruses in the togaviridae family. transmission of alphaviruses between and within species occurs mainly via the bite of an infected mosquito bite, giving alphaviruses a place among arboviruses, or arthropod-borne viruses. alphaviruses are found ...201627379085
wolbachia biocontrol strategies for arboviral diseases and the potential influence of resident wolbachia strains in mosquitoes.arboviruses transmitted by mosquitoes are a major cause of human disease worldwide. the absence of vaccines and effective vector control strategies has resulted in the need for novel mosquito control strategies. the endosymbiotic bacterium wolbachia has been proposed to form the basis for an effective mosquito biocontrol strategy. resident strains of wolbachia inhibit viral replication in drosophila fruit flies and induce a reproductive phenotype known as cytoplasmic incompatibility that allows ...201626925368
development of 2, 7-diamino-1, 8-naphthyridine (danp) anchored hairpin primers for rt-pcr detection of chikungunya virus infection.a molecular diagnostic platform with danp-anchored hairpin primer was developed and evaluated for the rapid and cost-effective detection of chikungunya virus (chikv) with high sensitivity and specificity. the molecule 2, 7-diamino-1, 8-naphthyridine (danp) binds to a cytosine-bulge and emits fluorescence at 450 nm when it is excited by 400 nm light. thus, by measuring the decline in fluorescence emitted from danp-primer complexes after pcr reaction, we could monitor the pcr progress. by adapting ...201627571201
detection of sindbis and inkoo virus rna in genetically typed mosquito larvae sampled in northern sweden.mosquito-borne viruses have a widespread distribution across the globe and are known to pose serious threats to human and animal health. the maintenance and dissemination of these viruses in nature are driven through horizontal and vertical transmission. in the temperate climate of northern sweden, there is a dearth of knowledge on whether mosquito-borne viruses that occur are transmitted transovarially. to gain a better understanding of mosquito-borne virus circulation and maintenance, mosquito ...201627159120
development and validation of a quantitative, one-step, multiplex, real-time reverse transcriptase pcr assay for detection of dengue and chikungunya viruses.dengue virus (denv) and chikungunya virus (chikv) are important human pathogens with common transmission vectors and similar clinical presentations. patient care may be impacted by the misdiagnosis of denv and chikv in areas where both viruses cocirculate. in this study, we have developed and validated a one-step multiplex reverse transcriptase pcr (rt-pcr) to simultaneously detect, quantify, and differentiate between four denv serotypes (pan-denv) and chikungunya virus. the assay uses taqman te ...201627098955
antagonism of the sodium-potassium atpase impairs chikungunya virus infection.chikungunya virus (chikv) is a reemerging alphavirus that has caused epidemics of fever, arthralgia, and rash worldwide. there are currently no licensed vaccines or antiviral therapies available for the prevention or treatment of chikv disease. we conducted a high-throughput, chemical compound screen that identified digoxin, a cardiac glycoside that blocks the sodium-potassium atpase, as a potent inhibitor of chikv infection. treatment of human cells with digoxin or a related cardiac glycoside, ...201627222471
identification of critical residues in hepatitis e virus macro domain involved in its interaction with viral methyltransferase and orf3 proteins.hepatitis e virus (hev) is a major cause of hepatitis in normal and organ transplant individuals. hev open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (x-domain), v, duf3729 and y. the macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand rna viruses, playing important roles in multiple cellular processes. towards understanding the function of th ...201627113483
vertical transmission of indian ocean lineage of chikungunya virus in aedes aegypti and aedes albopictus mosquitoes.the re-emergence of chikungunya (chik) fever in thailand has been caused by a novel lineage of chikungunya virus (chikv) termed the indian ocean lineage (iol). the aedes albopictus mosquito is thought to be a primary vector of chik fever in thailand, whereas ae. aegypti acts as a secondary vector of the virus. the vertical transmission is believed to be a primary means to maintain chikv in nature and may be associated with an increased risk of outbreak. therefore, the goal of this study was to a ...201627108077
dynamics of chikungunya virus cell entry unraveled by single-virus tracking in living cells.chikungunya virus (chikv) is a rapidly emerging mosquito-borne human pathogen causing major outbreaks in africa, asia, and the americas. the cell entry pathway hijacked by chikv to infect a cell has been studied previously using inhibitory compounds. there has been some debate on the mechanism by which chikv enters the cell: several studies suggest that chikv enters via clathrin-mediated endocytosis, while others show that it enters independently of clathrin. here we applied live-cell microscopy ...201626912616
assessment of productivity of culex spp. larvae (diptera: culicidae) in urban storm water catch basin system in wrocław (sw poland).in urban environments, catch basins serve as major developmental and resting sites for anthropophilic and zoophilic mosquitoes. however, the use of this habitat is inconsistent, with abundance of larvae varying significantly across catch basins at a fine spatial scale. during seasonal summer investigations on mosquito species composition, their spatial and temporal distribution and the environmental characteristic of the breeding sites in the underground storm drain systems of the wrocław urban ...201626809340
rainbow trout (oncorhynchus mykiss) muscle satellite cells are targets of salmonid alphavirus infection.sleeping disease in rainbow trout is characterized by an abnormal swimming behaviour of the fish which stay on their side at the bottom of the tanks. this sign is due to extensive necrosis and atrophy of red skeletal muscle induced by the sleeping disease virus (sdv), also called salmonid alphavirus 2. infections of humans with arthritogenic alphaviruses, such as chikungunya virus (chikv), are global causes of debilitating musculoskeletal diseases. the mechanisms by which the virus causes these ...201626743565
an updated checklist of mosquito species (diptera: culicidae) from madagascar.an updated checklist of 235 mosquito species from madagascar is presented. the number of species has increased considerably compared to previous checklists, particularly the last published in 2003 (178 species). this annotated checklist provides concise information on endemism, taxonomic position, developmental stages, larval habitats, distribution, behavior, and vector-borne diseases potentially transmitted. the 235 species belong to 14 genera: aedeomyia (3 species), aedes (35 species), anophel ...201627101839
an rna trapping mechanism in alphavirus mrna promotes ribosome stalling and translation initiation.during translation initiation, eukaryotic initiation factor 2 (eif2) delivers the met-trna to the 40s ribosomal subunit to locate the initiation codon (augi) of mrna during the scanning process. stress-induced eif2 phosphorylation leads to a general blockade of translation initiation and represents a key antiviral pathway in mammals. however, some viral mrnas can initiate translation in the presence of phosphorylated eif2 via stable rna stem-loop structures (dlp; downstream loop) located in thei ...201626984530
experimental piscine alphavirus rna recombination in vivo yields both viable virus and defective viral rna.rna recombination in non-segmented rna viruses is important for viral evolution and documented for several virus species through in vitro studies. here we confirm viral rna recombination in vivo using an alphavirus, the sav3 subtype of salmon pancreas disease virus. the virus causes pancreas disease in atlantic salmon and heavy losses in european salmonid aquaculture. atlantic salmon were injected with a sav3 6k-gene deleted cdna plasmid, encoding a non-viable variant of sav3, together with a he ...201627805034
perspectives for therapeutic hpv vaccine development.human papillomavirus (hpv) infections and associated diseases remain a serious burden worldwide. it is now clear that hpv serves as the etiological factor and biologic carcinogen for hpv-associated lesions and cancers. although preventative hpv vaccines are available, these vaccines do not induce strong therapeutic effects against established hpv infections and lesions. these concerns create a critical need for the development of therapeutic strategies, such as vaccines, to treat these existing ...201627809842
visualization of neutrophil extracellular traps and fibrin meshwork in human fibrinopurulent inflammatory lesions: iii. correlative light and electron microscopic study.neutrophil extracellular traps (nets) released from dead neutrophils at the site of inflammation represent webs of neutrophilic dna stretches dotted with granule-derived antimicrobial proteins, including lactoferrin, and play important roles in innate immunity against microbial infection. we have shown the coexistence of nets and fibrin meshwork in varied fibrinopurulent inflammatory lesions at both light and electron microscopic levels. in the present study, correlative light and electron micro ...201627917008
intercellular extensions are induced by the alphavirus structural proteins and mediate virus transmission.alphaviruses are highly organized enveloped rna viruses with an internal nucleocapsid surrounded by a membrane containing the e2 and e1 transmembrane proteins. alphavirus budding takes place at the plasma membrane and requires the interaction of the cytoplasmic domain of e2 with the capsid protein. here we used wt alphaviruses and sindbis virus in which e2 was fused to a fluorescent protein to characterize virus exit from host cells. our results show that alphavirus infection induced striking mo ...201627977778
chikungunya virus infectivity, rna replication and non-structural polyprotein processing depend on the nsp2 protease's active site cysteine residue.chikungunya virus (chikv), genus alphavirus, family togaviridae, has a positive-stand rna genome approximately 12 kb in length. in infected cells, the genome is translated into non-structural polyprotein p1234, an inactive precursor of the viral replicase, which is activated by cleavages carried out by the non-structural protease, nsp2. we have characterized chikv nsp2 using both cell-free and cell-based assays. first, we show that cys478 residue in the active site of chikv nsp2 is indispensable ...201627845418
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 ...201626874202
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