TitleAbstractYear(sorted descending)
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 universal next-generation sequencing protocol to generate noninfectious barcoded cdna libraries from high-containment rna viruses.several biosafety level 3 and/or 4 (bsl-3/4) pathogens are high-consequence, single-stranded rna viruses, and their genomes, when introduced into permissive cells, are infectious. moreover, many of these viruses are select agents (sas), and their genomes are also considered sas. for this reason, cdnas and/or their derivatives must be tested to ensure the absence of infectious virus and/or viral rna before transfer out of the bsl-3/4 and/or sa laboratory. this tremendously limits the capacity to ...201627822536
deah-rha helicase•znf cofactor systems in kinetoplastid rna editing and evolutionarily distant rna processes.multi-zinc finger proteins are an emerging class of cofactors in deah-rha rna helicases across highly divergent eukaryotic lineages. deah-rha helicase•zinc finger cofactor partnerships predate the split of kinetoplastid protozoa, which include several human pathogens, from other eukaryotic lineages 100-400 ma. despite a long evolutionary history, the prototypical deah-rha domains remain highly conserved. this short review focuses on a recently identified deah-rha helicase•zinc finger cofactor sy ...201627540585
a tale of two rnas during viral infection: how viruses antagonize mrnas and small non-coding rnas in the host cell.viral infection initiates an array of changes in host gene expression. many viruses dampen host protein expression and attempt to evade the host anti-viral defense machinery. host gene expression is suppressed at several stages of host messenger rna (mrna) formation including selective degradation of translationally competent messenger rnas. besides mrnas, host cells also express a variety of noncoding rnas, including small rnas, that may also be subject to inhibition upon viral infection. in th ...201627271653
a glance at subgenomic flavivirus rnas and micrornas in flavivirus infections.the family flaviviridae comprises a wide variety of viruses that are distributed worldwide, some of which are associated with high rates of morbidity and mortality. there are neither vaccines nor antivirals for most flavivirus infections, reinforcing the importance of research on different aspects of the viral life cycle. during infection, cytoplasmic accumulation of rna fragments mainly originating from the 3' utrs, which have been designated subgenomic flavivirus rnas (sfrnas), has been detect ...201627233361
entry sites of venezuelan and western equine encephalitis viruses in the mouse central nervous system following peripheral infection.venezuelan and western equine encephalitis viruses (veev and weev; alphavirus; togaviridae) are mosquito-borne pathogens causing central nervous system (cns) disease in humans and equids. adult cd-1 mice also develop cns disease after infection with veev and weev. adult cd-1 mice infected by the intranasal (i.n.) route, showed that veev and weev enter the brain through olfactory sensory neurons (osns). in this study, we injected the mouse footpad with recombinant weev (mcmillan) or veev (subtype ...201627053560
suppression of usp18 potentiates the anti-hbv activity of interferon alpha in hepg2.2.15 cells via jak/stat signaling.ubiquitin-specific protease 18 (usp18, also known as ubp43) has both interferon stimulated gene 15 (isg15) dependent and isg15-independent functions. by silencing the expression of usp18 in hepg2.2.15 cells, we studied the effect of usp18 on the anti-hbv activity of ifn-f and demonstrated that knockdown of usp18 significantly inhibited the hbv expression and increased the expression of isgs. levels of hepatitis b virus surface antigen (hbsag), hepatitis b virus e antigen (hbeag), hbv dna and int ...201627227879
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
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
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
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
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
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
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
the modulation of apoptotic pathways by gammaherpesviruses.apoptosis or programmed cell death is a tightly regulated process fundamental for cellular development and elimination of damaged or infected cells during the maintenance of cellular homeostasis. it is also an important cellular defense mechanism against viral invasion. in many instances, abnormal regulation of apoptosis has been associated with a number of diseases, including cancer development. following infection of host cells, persistent and oncogenic viruses such as the members of the gamma ...201627199919
the role of climatic and density dependent factors in shaping mosquito population dynamics: the case of culex pipiens in northwestern italy.culex pipiens mosquito is a species widely spread across europe and represents a competent vector for many arboviruses such as west nile virus (wnv), which has been recently circulating in many european countries, causing hundreds of human cases. in order to identify the main determinants of the high heterogeneity in cx. pipiens abundance observed in piedmont region (northwestern italy) among different seasons, we developed a density-dependent stochastic model that takes explicitly into account ...201627105065
infection pattern and transmission potential of chikungunya virus in two new world laboratory-adapted aedes aegypti strains.chikungunya virus (chikv) is an emerging mosquito-borne virus belonging to the togaviridae, which is transmitted to humans by aedes aegypti and ae. albopictus. we describe the infection pattern of chikv in two new world ae. aegypti strains, hwe and orl. both mosquito strains were susceptible to the virus but showed different infection patterns in midguts and salivary glands. even though acquisition of a bloodmeal showed moderate levels of apoptosis in midgut tissue, there was no obvious addition ...201627102548
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
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
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
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
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 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
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
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
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
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 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
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
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
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
an updated checklist of mosquito species (diptera: culicidae) from 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
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
pirna pathway is not required for antiviral defense in drosophila melanogaster.since its discovery, rna interference has been identified as involved in many different cellular processes, and as a natural antiviral response in plants, nematodes, and insects. in insects, the small interfering rna (sirna) pathway is the major antiviral response. in recent years, the piwi-interacting rna (pirna) pathway also has been implicated in antiviral defense in mosquitoes infected with arboviruses. using drosophila melanogaster and an array of viruses that infect the fruit fly acutely o ...201627357659
who regulates whom? an overview of rna granules and viral infections.after viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mrna translation (protein synthesis) and the assembly of rna granules. two of these rna granules have been well characterized in yeast and mammalian cells, stress granules (sgs), which are translationally silent sites of rna triage and processing bodies (pbs), which are involved in mrna degradation. this review discusses the ...201627367717
alphavirus restriction by ifitm proteins.interferon inducible transmembrane proteins (ifitms) are broad-spectrum antiviral factors. in cell culture the entry of many enveloped viruses, including orthomyxo-, flavi-, and filoviruses, is inhibited by ifitms, though the mechanism(s) involved remain unclear and may vary between viruses. we demonstrate that sindbis and semliki forest virus (sfv), which both use endocytosis and acid-induced membrane fusion in early endosomes to infect cells, are restricted by the early endosomal ifitm3. the l ...201627219333
adapting the stress response: viral subversion of the mtor signaling pathway.the mammalian target of rapamycin (mtor) is a central regulator of gene expression, translation and various metabolic processes. multiple extracellular (growth factors) and intracellular (energy status) molecular signals as well as a variety of stressors are integrated into the mtor pathway. viral infection is a significant stress that can activate, reduce or even suppress the mtor signaling pathway. consequently, viruses have evolved a plethora of different mechanisms to attack and co-opt the m ...201627231932
glial cell activation, recruitment, and survival of b-lineage cells following mcmv brain infection.chemokines produced by reactive glia drive migration of immune cells and previous studies from our laboratory have demonstrated that cd19(+) b cells infiltrate the brain. in this study, in vivo and in vitro experiments investigated the role of reactive glial cells in recruitment and survival of b-lineage cells in response to (murine cytomegalovirus) mcmv infection.201627207308
making bunyaviruses talk: interrogation tactics to identify host factors required for infection.the identification of host cellular genes that act as either proviral or antiviral factors has been aided by the development of an increasingly large number of high-throughput screening approaches. here, we review recent advances in which these new technologies have been used to interrogate host genes for the ability to impact bunyavirus infection, both in terms of technical advances as well as a summary of biological insights gained from these studies.201627187446
dengue virus reporter replicon is a valuable tool for antiviral drug discovery and analysis of virus replication mechanisms.dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (denv), a member of the flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. however, no specific antiviral drug or licensed vaccine currently targets denv infection. the replicon system has all the factors needed for viral replication in cells. since the development of replicon systems, transient and stable reporter replicon ...201627164125
role of tspan9 in alphavirus entry and early endosomes.alphaviruses are small enveloped rna viruses that infect cells via clathrin-mediated endocytosis and low-ph-triggered fusion in the early endosome. using a small interfering rna (sirna) screen in human cells, we previously identified tspan9 as a host factor that promotes infection by the alphaviruses sindbis virus (sinv), semliki forest virus (sfv), and chikungunya virus (chikv). depletion of tspan9 specifically decreases sfv membrane fusion in endosomes. tspan9 is a member of the tetraspanin fa ...201626865714
sirna screen identifies trafficking host factors that modulate alphavirus infection.little is known about the repertoire of cellular factors involved in the replication of pathogenic alphaviruses. to uncover molecular regulators of alphavirus infection, and to identify candidate drug targets, we performed a high-content imaging-based sirna screen. we revealed an actin-remodeling pathway involving rac1, pip5k1- α, and arp3, as essential for infection by pathogenic alphaviruses. infection causes cellular actin rearrangements into large bundles of actin filaments termed actin foci ...201627031835
versatile trans-replication systems for chikungunya virus allow functional analysis and tagging of every replicase protein.chikungunya virus (chikv; genus alphavirus, family togaviridae) has recently caused several major outbreaks affecting millions of people. there are no licensed vaccines or antivirals, and the knowledge of the molecular biology of chikv, crucial for development of efficient antiviral strategies, remains fragmentary. chikv has a 12 kb positive-strand rna genome, which is translated to yield a nonstructural (ns) or replicase polyprotein. chikv structural proteins are expressed from a subgenomic rna ...201626963103
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
inactivation of the type i interferon pathway reveals long double-stranded rna-mediated rna interference in mammalian cells.rna interference (rnai) elicited by long double-stranded (ds) or base-paired viral rna constitutes the major mechanism of antiviral defence in plants and invertebrates. in contrast, it is controversial whether it acts in chordates. rather, in vertebrates, viral rnas induce a distinct defence system known as the interferon (ifn) response. here, we tested the possibility that the ifn response masks or inhibits antiviral rnai in mammalian cells. consistent with that notion, we find that sequence-sp ...201627815315
rabies control and treatment: from prophylaxis to strategies with curative potential.rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. in the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. unlike the conventio ...201627801824
new world and old world alphaviruses have evolved to exploit different components of stress granules, fxr and g3bp proteins, for assembly of viral replication complexes.the positive-strand rna viruses initiate their amplification in the cell from a single genome delivered by virion. this single rna molecule needs to become involved in replication process before it is recognized and degraded by cellular machinery. in this study, we show that distantly related new world and old world alphaviruses have independently evolved to utilize different cellular stress granule-related proteins for assembly of complexes, which recruit viral genomic rna and facilitate format ...201627509095
pathogenic chikungunya virus evades b cell responses to establish persistence.chikungunya virus (chikv) and related alphaviruses cause epidemics of acute and chronic musculoskeletal disease. to investigate the mechanisms underlying the failure of immune clearance of chikv, we studied mice infected with an attenuated chikv strain (181/25) and the pathogenic parental strain (af15561), which differ by five amino acids. whereas af15561 infection of wild-type mice results in viral persistence in joint tissues, 181/25 is cleared. in contrast, 181/25 infection of μmt mice lackin ...201627452455
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
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
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
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
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
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
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
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
emerging role of lipid droplets in aedes aegypti immune response against bacteria and dengue 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
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
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
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
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
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