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the proteins expressed by different isolates of drosophila c virus.isolates of drosophila c virus (dcv) from drosophila flies obtained in geographically different regions were adapted to growth in drosophila tissue culture cells. the viruses, purified from tissue culture cells, were shown to be serologically related to one of the isolates ("o" from ouarzazate, morocco). analysis of the structural proteins by polyacrylamide gel electrophoresis demonstrated differences between the isolates. labelling intracellular proteins of infected drosophila melanogaster cell ...19826297428
cell-free translation of drosophila c virus rna: identification of a virus protease activity involved in capsid protein synthesis and further studies on in vitro processing of cricket paralysis virus specified proteins.drosophila c virus rna acted as mrna in rabbit reticulocyte lysates and directed the synthesis of at least one capsid protein and a number of higher molecular weight proteins. kinetic analysis by pulse-chase experiments showed that a number of high molecular weight products acted as precursors to the capsid protein(s). various dilution experiments were performed which showed that the virus specified a protease activity essential for the correct processing of precursors to give the capsid protein ...19836307220
drosophila-host genetic control of susceptibility to drosophila c virus.interactions between drosophila c virus (dcv) and its natural host, drosophila melanogaster, were investigated using 15 geographical population samples infected by intraabdominal inoculation. these strains derived from natural populations of d. melanogaster differed in susceptibility to the dcvc. one strain was "partially tolerant". isofemale lines obtained from one susceptible and one partially tolerant strain were studied. the partially tolerant phenotype was dominant, and there was no differe ...19957498770
determining the nucleotide sequence and capsid-coding region of himetobi p virus: a member of a novel group of rna viruses that infect insects.we determined the complete genome sequence of himetobi p virus (hipv), an insect picorna-like virus, which was isolated from the small brown planthopper, laodelphax striatellus. the genome of hipv consists of 9,275 nucleotides excluding the poly (a) tail, and contains two large open reading frames (orfs), which were separated by a 176-nucleotide noncoding region. the deduced amino acid sequence of the first orf contains core motifs of picornaviral helicase, protease, and rna-dependent rna polyme ...199910550677
analysis of the complete genome sequence of black queen-cell virus, a picorna-like virus of honey bees.a virus with picorna-like biophysical properties was isolated from south african honey bees. on the basis of serology, it was identified as an isolate of black queen-cell virus (bqcv). nucleotide sequence analysis revealed an 8550 nt polyadenylated genome containing two large orfs. the 5'-proximal orf (orf 1) represented 4968 nt while the 3'-proximal orf (orf 2) represented 2562 nt. the orfs were separated by a 208 nt intergenic region and were flanked by a 657 nt 5'-untranslated region and a 15 ...200010900051
nucleotide sequence analysis shows that rhopalosiphum padi virus is a member of a novel group of insect-infecting rna viruses.rhopalosiphum padi virus (rhpv) is an aphid virus that has been considered a member of the picornaviridae based on physicochemical properties. the 10,011-nt polyadenylated rna genome of rhpv was completely sequenced. analysis of the sequence revealed the presence of two open reading frames (orfs). the predicted amino acid sequence of orf1, representing the first 6600 nt of the rhpv genome, showed significant similarity to the nonstructural proteins of several plant and animal rna viruses. direct ...19989527915
drosophila c virus: experimental study of infectious yields and underlying pathology in drosophila melanogaster laboratory populations.the underlying pathology of a nonhereditary virus, the drosophila c virus, was studied. this study was related to the contamination routes (ingestion or contact) and developmental timing. when oral contamination occurred at the first larval instar: (1) the flies were contaminated, (2) the flies which had developed the most rapidly were the most infected, (3) in newly emerged females, the level of virus was higher than in newly emerged males, (4) when infected flies were reared on virus-free medi ...19957745279
location of drosophila c virus target organs in drosophila host population by an immunofluorescence technique.using the immunofluorescence technique we attempted to locate, in the drosophila host, drosophila c virus (dcv) target organs after injection of adult flies. two kinds of organs were infected: those which play a role in reproductive function, including the fat body and follicular cells, and other, including thoracic muscle fibers, tracheal cells, and the digestive tract. these organs correspond to those found in previous tests. fat body proteins of a dcv-free host population seemed to cross-reac ...19902261574
a simple vacuum dot-blot hybridisation assay for the detection of drosophila a and c viruses in single drosophila.specific cdna clones were constructed from the single stranded rna genome of australian isolates of both drosophila a and c viruses. these clones were used to develop a nucleic acid hybridisation assay capable of detecting reliably 3.9 ng of dav and 19.3 ng of dcv virus particles, respectively. the sensitivity of the assays were largely unaffected by soluble host material. single drosophila naturally infected or artificially inoculated with dav or dcv were found to contain in excess of 130 ng of ...19921644892
serological relations between twelve small rna viruses of insects.serological tests were done to examine the relationships between twelve picorna-like viruses of insects. the results of the tests indicated that the majority of the viruses are unrelated. however, cricket paralysis virus, isolated from australian wild field crickets, appeared to be identical to drosophila c virus, independently isolated in france. cricket paralysis virus was infective for adults of drosophila melanogaster and its infectivity towards galleria melonella was neutralised by drosophi ...1976816992
characterization of the drosophila c virus.some properties of drosophila c virus (dcv), a non-occluded isometric virus, have been studied. the virus particles were 30 nm in diam., their sedimentation coefficient was 153s and their buoyant density was 1-34 g/ml in caesium chloride in the ph range 7 to 9. these particles contained about 31% ribonucleic acid (rna) and 69% protein. the reaction of formaldehyde with dcv particles suggested that the rna in situ is single-stranded. the infectivity of dcv was stable at ph 3. the virus capsid con ...1977190345
cricket paralysis virus and drosophila c virus: serological analysis and comparison of capsid polypeptides and host range. 197898592
characterization of a small rna-containing virus in field-collected larvae of the tussock moth, lymantria ninayi, from papua new guinea.field-collected larvae of the tussock moth, lymantria ninayi, a major pest of exotic pines in papua new guinea, were found to contain a small rna-containing virus with a diameter of 29 nm and a buoyant density of 1.32 g/ml. the rna was single stranded, had a molecular weight of 2.8 x 10, and was polyadenylated. virion rna stimulated an in vitro translation system, and high-molecular-weight proteins were produced. purified virions contained four structural proteins with molecular weights of 43,00 ...198416346620
antiviral immunity in drosophila requires systemic rna interference spread.multicellular organisms evolved sophisticated defence systems to confer protection against pathogens. an important characteristic of these immune systems is their ability to act both locally at the site of infection and at distal uninfected locations. in insects, such as drosophila melanogaster, rna interference (rnai) mediates antiviral immunity. however, the antiviral rnai defence in flies seems to be a local, cell-autonomous process, as flies are thought to be unable to generate a systemic rn ...200919204732
the bacterial symbiont wolbachia induces resistance to rna viral infections in drosophila melanogaster.wolbachia are vertically transmitted, obligatory intracellular bacteria that infect a great number of species of arthropods and nematodes. in insects, they are mainly known for disrupting the reproductive biology of their hosts in order to increase their transmission through the female germline. in drosophila melanogaster, however, a strong and consistent effect of wolbachia infection has not been found. here we report that a bacterial infection renders d. melanogaster more resistant to drosophi ...200819222304
the jak-stat signaling pathway is required but not sufficient for the antiviral response of drosophila.the response of drosophila to bacterial and fungal infections involves two signaling pathways, toll and imd, which both activate members of the transcription factor nf-kappab family. here we have studied the global transcriptional response of flies to infection with drosophila c virus. viral infection induced a set of genes distinct from those regulated by the toll or imd pathways and triggered a signal transducer and activator of transcription (stat) dna-binding activity. genetic experiments sh ...200516086017
entry is a rate-limiting step for viral infection in a drosophila melanogaster model of pathogenesis.the identification of host factors that control susceptibility to infection has been hampered by a lack of amenable genetic systems. we established an in vivo model to determine the host factors that control pathogenesis and identified viral entry as a rate-limiting step for infection. we infected drosophila melanogaster cells and adults with drosophila c virus and found that the clathrin-mediated endocytotic pathway is essential for both infection and pathogenesis. heterozygosity for mutations ...200414691479
sequence analysis and genomic organization of aphid lethal paralysis virus: a new member of the family dicistroviridae.the complete nucleotide sequence of the genomic rna of an aphid-infecting virus, aphid lethal paralysis virus (alpv), has been determined. the genome is 9812 nt in length and contains two long open reading frames (orfs), which are separated by an intergenic region of 163 nt. the first orf (5' orf) is preceded by an untranslated leader sequence of 506 nt, while an untranslated region of 571 nt follows the second orf (3' orf). the deduced amino acid sequences of the 5' orf and 3' orf products resp ...200212466490
nucleotide sequence of 3'-end of the genome of taura syndrome virus of shrimp suggests that it is related to insect picornaviruses.taura syndrome disease, caused by taura syndrome virus (tsv), is one of the most important viral diseases of penaeid shrimp in the western hemisphere resulting in catastrophic disease epidemics in farmed shrimp. we have cloned and sequenced a 3278 bp cdna representing the 3' end of the tsv genome. sequence analyses revealed that frame + 2 had the longest open reading (orf) frame. this frame contained a 5'-terminal 19 non-coding bases followed by an orf from nucleotides 20 to 3053 (encoding 1011 ...200111448031
host range and specificity of the drosophila c virus.the drosophila c virus (dcv) is a common and well-studied drosophila pathogen. although natural infections are known from drosophila melanogaster and d. simulans, and artificial infections have been reported from several drosophila species and other insects, it remains unclear to date whether dcv infections also occur naturally in other drosophila species.201020865043
a tertiary structure model of the internal ribosome entry site (ires) for methionine-independent initiation of translation.cricket paralysis-like viruses have a dicistronic positive-strand rna genome. these viruses produce capsid proteins through internal ribosome entry site (ires)-mediated translation. the ires element of one of these viruses, plautia stall intestine virus (psiv), forms a pseudoknot immediately upstream from the capsid coding sequence, and initiates translation from other than methionine. previously, we estimated that the ires element of psiv consists of seven stem-loops using the program mfold; ho ...200111233983
molecular phylogenetics and the classification of honey bee viruses.we present the phylogenetic relationships of several picorna-like rna viruses found in honey bees, with respect to 13 additional plant and animal positive-strand rna viruses. most of the honey bee viruses fall into an unnamed family of insect rna viruses typified by the drosophila c virus. different bee viruses are broadly distributed within this group, suggesting either that the ability to infect honey bees has evolved multiple times, or that these viruses are generalistic in their abilities to ...200011087089
analysis of the complete genome sequence of acute bee paralysis virus shows that it belongs to the novel group of insect-infecting rna viruses.the complete genome sequence of acute bee paralysis virus (abpv) was determined. the 9470 nucleotide, polyadenylated rna genome encoded two open reading frames (orf1 and orf2), which were separated by 184 nucleotides. the deduced amino acid sequence of the 5' orf1 (nucleotides 605 to 6325) showed significant similarity to the rna-dependent rna polymerase, helicase, and protease domains of viruses from the picornavirus, comovirus, calicivirus, and sequivirus families, as well as to a novel group ...200011080493
virulence variability of the drosophila c virus and effects of the microparasite on demographic parameters of the host (drosophila melanogaster).we carried out experiments with the drosophila c virus (dcv), a nonhereditary virus acting on demographic parameters of infected drosophila host populations. it is well known that dcv increases mortality rate, decreases developmental time, and increases daily fecundity. as usual for drosophila viruses, the dcv was multiplied in vivo. in this study we tested the hypothesis of virulence variability in dcv strains by isolating different stocks of the virus. the flies were tested for susceptibility ...200010772327
nucleotide sequence analysis of triatoma virus shows that it is a member of a novel group of insect rna viruses.triatoma virus (trv) is the only virus described to date that infects triatomines, and has previously been considered to be a member of the family picornaviridae on the basis of physico-chemical properties. the genome of trv was sequenced completely (9010 nt). analysis of the sequence revealed the presence of two large open reading frames (orfs). the predicted amino acid sequence of orf1 (nt 549-5936) showed significant similarity to the non-structural proteins of several animal and plant rna vi ...200010725445
molecular characterization of drosophila c virus isolates.reverse transcription coupled with polymerase chain reaction and restriction enzyme analysis was used to characterize 12 drosophila c virus isolates from geographically different regions. a 1.2-kb fragment was amplified from cdna and profiles from digestion with 20 restriction enzymes were generated. analysis of the restriction fragment data gave estimates of nucleotide divergence of 0-10% between isolates. the isolates were grouped on the basis of genetic distance estimates derived from the res ...199910222177
an insect picorna-like virus, plautia stali intestine virus, has genes of capsid proteins in the 3' part of the genome.the complete genome of an insect picorna-like virus, plautia stali intestine virus (psiv), was cloned and sequenced. the genome had 8797 nucleotides including two consecutive long open reading frames. the deduced amino acid sequence of the first open reading frame (nucleotides 571 to 6003) contained conserved sequence motifs for picornavirus rna helicase, cysteine protease, and rna-dependent rna polymerase. the order of the three motifs in the genome was the same as those of mammalian picornavir ...19989581777
the toll-dorsal pathway is required for resistance to viral oral infection in drosophila.pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. here we investigate the role of the toll pathway in resistance to oral viral infection in d. melanogaster. we show that several toll pathway components, including spätzle, toll, pelle and the nf-kb-like transcription factor dorsal, are required to resist oral ...201425473839
essential function in vivo for dicer-2 in host defense against rna viruses in drosophila.the fruit fly drosophila melanogaster is a model system for studying innate immunity, including antiviral host defense. infection with drosophila c virus triggers a transcriptional response that is dependent in part on the jak kinase hopscotch. here we show that successful infection and killing of drosophila with the insect nodavirus flock house virus was strictly dependent on expression of the viral protein b2, a potent inhibitor of processing of double-stranded rna mediated by the essential rn ...200616554838
the novel genome organization of the insect picorna-like virus drosophila c virus suggests this virus belongs to a previously undescribed virus family.the complete nucleotide sequence of the genomic rna from the insect picorna-like virus drosophila c virus (dcv) was determined. the dcv sequence predicts a genome organization different to that of other rna virus families whose sequences are known. the single-stranded positive-sense genomic rna is 9264 nucleotides in length and contains two large open reading frames (orfs) which are separated by 191 nucleotides. the 5' orf contains regions of similarities with the rna-dependent rna polymerase, h ...19989460942
[c virus of drosophila and dynamics of host population].drosophila melanogaster populations are naturally infected by the drosophila c virus (dcv). ingestion of this non-hereditary virus early in the life-cycle has a positive effect. demographic parameters measured on dcv-free and dcv-infected populations of the same genotype enabled us to compute the population growth rates (multiplication rates) by means of matrix models. the dcv-infected sample had a larger growth rate both for low and high larval densities. since it is not possible to experiment ...19969011323
wolbachia-mediated antiviral protection in drosophila larvae and adults following oral infection.understanding viral dynamics in arthropods is of great importance when designing models to describe how viral spread can influence arthropod populations. the endosymbiotic bacterium wolbachia spp., which is present in up to 40% of all insect species, has the ability to alter viral dynamics in both drosophila spp. and mosquitoes, a feature that in mosquitoes may be utilized to limit spread of important arboviruses. to understand the potential effect of wolbachia on viral dynamics in nature, it is ...201526407882
dietary cholesterol modulates pathogen blocking by wolbachia.the bacterial endosymbiont wolbachia pipientis protects its hosts from a range of pathogens by limiting their ability to form infections inside the insect. this "pathogen blocking" could be explained by innate immune priming by the symbiont, competition for host-derived resources between pathogens and wolbachia, or the direct modification of the cell or cellular environment by wolbachia. recent comparative work in drosophila and the mosquito aedes aegypti has shown that an immune response is not ...201323825950
unveiling time in dose-response models to infer host susceptibility to pathogens.the biological effects of interventions to control infectious diseases typically depend on the intensity of pathogen challenge. as much as the levels of natural pathogen circulation vary over time and geographical location, the development of invariant efficacy measures is of major importance, even if only indirectly inferrable. here a method is introduced to assess host susceptibility to pathogens, and applied to a detailed dataset generated by challenging groups of insect hosts (drosophila mel ...201425121762
wolbachia variants induce differential protection to viruses in drosophila melanogaster: a phenotypic and phylogenomic analysis.wolbachia are intracellular bacterial symbionts that are able to protect various insect hosts from viral infections. this tripartite interaction was initially described in drosophila melanogaster carrying wmel, its natural wolbachia strain. wmel has been shown to be genetically polymorphic and there has been a recent change in variant frequencies in natural populations. we have compared the antiviral protection conferred by different wmel variants, their titres and influence on host longevity, i ...201324348259
transcriptional profiling of drosophila s2 cells in early response to drosophila c virus.the innate immune response like phagocytosis, encapsulation and antimicrobial peptide (amp) production often occur in the early stage of host-pathogen interactions in drosophila melanogaster. to investigate the drosophila early immune response to drosophila c virus, we characterized the dcv infection-response transcriptome of drosophila schneider 2 (s2) cells at one hour post inoculation.201323803447
a suggested taxonomy and nomenclature for the cricket paralysis and drosophila c virus complex.biophysical, biological, and serological characters are presented which in combination allow isolates of cricket paralysis virus (crpv) and drosophila c virus (dcv) to be separated and seven distinct strains of crpv to be defined. reference isolates for crpv and dcv are suggested along with a system of nomenclature that allows the passage history of a particular isolate to be easily described.19948176243
copi activity coupled with fatty acid biosynthesis is required for viral replication.during infection by diverse viral families, rna replication occurs on the surface of virally induced cytoplasmic membranes of cellular origin. how this process is regulated, and which cellular factors are required, has been unclear. moreover, the host-pathogen interactions that facilitate the formation of this new compartment might represent critical determinants of viral pathogenesis, and their elucidation may lead to novel insights into the coordination of vesicular trafficking events during i ...200617040126
the rna silencing endonuclease argonaute 2 mediates specific antiviral immunity in drosophila melanogaster.most organisms have evolved defense mechanisms to protect themselves from viruses and other pathogens. arthropods lack the protein-based adaptive immune response found in vertebrates. here we show that the central catalytic component of the rna-induced silencing complex (risc), the nuclease argonaute 2 (ago-2), is essential for antiviral defense in adult drosophila melanogaster. ago-2-defective flies are hypersensitive to infection with a major fruit fly pathogen, drosophila c virus (dcv), and w ...200617079687
modifications of mean ovariole number, fresh weight of adult females and developmental time in drosophila melanogaster induced by drosophila c virus.drosophila c virus, a picornavirus that has some influence on ovarian morphogenesis, was discovered in a french strain of drosophila melanogaster. when the strain was infected by drosophila c virus (dcv), the mean number of ovarian tubes and weights of the adult females increased, but the developmental time from egg to imago decreased. the maternal effects observed when dcv was present disappeared when the strain was dcv free but were restored by experimental contamination.198417246225
drosophila a virus is an unusual rna virus with a t=3 icosahedral core and permuted rna-dependent rna polymerase.the vinegar fly, drosophila melanogaster, is a popular model for the study of invertebrate antiviral immune responses. several picorna-like viruses are commonly found in both wild and laboratory populations of d. melanogaster. the best-studied and most pathogenic of these is the dicistrovirus drosophila c virus. among the uncharacterized small rna viruses of d. melanogaster, drosophila a virus (dav) is the least pathogenic. historically, dav has been labelled as a picorna-like virus based on its ...200919474243
molecular analysis of capsid protein of homalodisca coagulata virus-1, a new leafhopper-infecting virus from the glassy-winged sharpshooter, homalodisca coagulata.a new virus that infects and causes increased mortality in leafhoppers was isolated from the glassy-winged sharpshooter, homalodisca coagulata (say) (hemiptera: cicadellidae). the virus, named homalodisca coagulata virus -1, hocv-1, was associated with increased mortality of cultured 5(th) instar h. coagulata. to identify the presence of h. coagulata viral pathogens, cdna expression libraries were made from adult and nymphs. analysis using reverse transcriptase pcr demonstrated that the virus wa ...200619537993
variation in antiviral protection mediated by different wolbachia strains in drosophila simulans.drosophila c virus (dcv) is a natural pathogen of drosophila and a useful model for studying antiviral defences. the drosophila host is also commonly infected with the widespread endosymbiotic bacteria wolbachia pipientis. when dcv coinfects wolbachia-infected d. melanogaster, virus particles accumulate more slowly and virus induced mortality is substantially delayed. considering that wolbachia is estimated to infect up to two-thirds of all insect species, the observed protective effects of wolb ...200919911047
cricket paralysis virus antagonizes argonaute 2 to modulate antiviral defense in drosophila.insect viruses have evolved strategies to control the host rnai antiviral defense mechanism. in nature, drosophila melanogaster c virus (dcv) infection causes low mortality and persistent infection, whereas the closely related cricket paralysis virus (crpv) causes a lethal infection. we show that these viruses use different strategies to modulate the host rnai defense machinery. the dcv rnai suppressor (dcv-1a) binds to long double-stranded rna and prevents processing by dicer2. in contrast, the ...201020400949
ectopic expression of an endoparasitic wasp venom protein in drosophila melanogaster affects immune function, larval development and oviposition.endoparasitic hymenoptera inject maternal factors into the host, along with their eggs, to subvert the host immune system. the venom protein, vn50, previously characterized from the wasp cotesia rubecula inhibits prophenoloxidase activation in its host pieris rapae and in another lepidopteran, manduca sexta. we generated a stable line in the model insect, drosophila melanogaster, which ectopically expresses vn50. results indicated that vn50 expression accelerates larval development, increases ov ...201020408903
identification of viral suppressors of rnai by a reporter assay in drosophila s2 cell culture.the rna interference (rnai) pathway plays an important role in antiviral immunity in insects. to -counteract the rnai-mediated immune response of their hosts, several insect viruses, such as flock house virus, drosophila c virus, and cricket paralysis virus, encode potent viral suppressors of rnai (vsrs). because of the importance of rnai in antiviral defense in insects, other insect viruses are likely to encode vsrs as well. in this chapter, we describe a detailed protocol for an rnai reporter ...201121431687
ex vivo production of autologous whole inactivated hiv-1 for clinical use in therapeutic vaccines.this study provides a detailed description and characterization of the preparation of individualized lots of autologous heat inactivated hiv-1 virions used as immunogen in a clinical trial designed to test an autologous dendritic-cell-based therapeutic hiv-1 vaccine (clinical trial dcv-2, nct00402142). for each participant, ex vivo isolation and expansion of primary virus were performed by co-culturing cd4-enriched pbmcs from the hiv-1-infected patient with pbmc from hiv-seronegative unrelated h ...201121679735
a dna virus of drosophila.little is known about the viruses infecting most species. even in groups as well-studied as drosophila, only a handful of viruses have been well-characterized. a viral metagenomic approach was used to explore viral diversity in 83 wild-caught drosophila innubila, a mushroom feeding member of the quinaria group. a single fly that was injected with, and died from, drosophila c virus (dcv) was added to the sample as a control. two-thirds of reads in the infected sample had dcv as the best blast hit ...201122053195
genome-wide rnai screen reveals a specific sensitivity of ires-containing rna viruses to host translation inhibition.the widespread class of rna viruses that utilize internal ribosome entry sites (iress) for translation include poliovirus and hepatitis c virus. to identify host factors required for ires-dependent translation and viral replication, we performed a genome-wide rnai screen in drosophila cells infected with drosophila c virus (dcv). we identified 66 ribosomal proteins that, when depleted, specifically inhibit dcv growth, but not a non-ires-containing rna virus. moreover, treatment of flies with a t ...200515713840
drosophila c virus cycle during the development of two drosophila melanogaster strains (charolles and champetières) after larval contamination by food.drosophila c virus (dcv) cycle during drosophila melanogaster development was studied after feeding contamination at the first, most sensitive, instar (l1). two drosophila strains were examined and compared. presence of dcvc in apparently healthy animals (l3 larvae bred on a contaminated rearing medium and adults coming from larvae which were grown on medium containing dcvc) was demonstrated by biological tests. using the immunofluorescence technique, dcv was exhibited in the diseased charolles ...19921300196
mutability studies in two drosophila melanogaster isogenic stocks, endemic for c picornavirus and virus-free.a virus-free drosophila stock was obtained by outer disinfection of eggs from dcv-contaminated females. the healthy flies exhibited 3 times less lethal mutations on the x chromosome than did the diseased flies. in addition, on x and 2nd chromosomes, the mutability of the infected males was 2-3 times lower than that of the infected females. the natural viruses of drosophila are partially responsible for the rate of mutations occurring in the wild populations of this insect.19826799802
combinations of lambda interferon with direct-acting antiviral agents are highly efficient in suppressing hepatitis c virus replication.the clinical efficacy of a pegylated form of human lambda 1 interferon (ifn-λ1; also referred to herein as lambda) has been demonstrated in patients chronically infected with hepatitis c virus (hcv) representing genotypes 1 through 4. in these proof-of-concept studies, lambda showed an improved safety profile compared to the pegylated form of alpha interferon (referred to herein as alfa). in the study described in this report, an assessment of the in vitro antiviral activity of type iii ifns tow ...201223274666
insect antiviral innate immunity: pathways, effectors, and connections.insects are infected by a wide array of viruses some of which are insect restricted and pathogenic, and some of which are transmitted by biting insects to vertebrates. the medical and economic importance of these viruses heightens the need to understand the interaction between the infecting pathogen and the insect immune system in order to develop transmission interventions. the interaction of the virus with the insect host innate immune system plays a critical role in the outcome of infection. ...201324120681
broad rna interference-mediated antiviral immunity and virus-specific inducible responses in drosophila.the fruit fly drosophila melanogaster is a good model to unravel the molecular mechanisms of innate immunity and has led to some important discoveries about the sensing and signaling of microbial infections. the response of drosophila to virus infections remains poorly characterized and appears to involve two facets. on the one hand, rna interference involves the recognition and processing of dsrna into small interfering rnas by the host rnase dicer-2 (dcr-2), whereas, on the other hand, an indu ...201223255357
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
drosophila c virus systemic infection leads to intestinal obstruction.drosophila c virus (dcv) is a positive-sense rna virus belonging to the dicistroviridae family. this natural pathogen of the model organism drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both rna interference and inducible responses. although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. here, we characterize the ...201425253354
previous exposure to an rna virus does not protect against subsequent infection in drosophila melanogaster.immune priming has been shown to occur in a wide array of invertebrate taxa, with individuals exposed to a pathogen showing increased protection upon subsequent exposure. however, the mechanisms underlying immune priming are poorly understood. the antiviral rnai response in drosophila melanogaster is an ideal candidate for providing a specific and acquired response to subsequent infection. we exposed d. melanogaster to two challenges of a virus known to produce an antiviral rnai response, to exa ...201324040086
male-killing wolbachia do not protect drosophila bifasciata against viral infection.insect symbionts employ multiple strategies to enhance their spread through populations, and some play a dual role as both a mutualist and a reproductive manipulator. it has recently been found that this is the case for some strains of wolbachia, which both cause cytoplasmic incompatibility and protect their hosts against viruses. here, we carry out the first test as to whether a male-killing strain of wolbachia also provides a direct benefit to its host by providing antiviral protection to its ...201222376177
[haploadaptivity of tumor suppressor lgl and ontogenesis in drosophila melanogaster: increased survival rate and life span under stress conditions].mutations of tumor suppressor lgl induce neuroblastoma and malignant transformation of epithelial larval tissues in drosophila. we have already shown that heterozygotes for lethal null variants lgl/+ are widespread in natural populations. in order to elucidate this paradox, we analyzed the parameters of biological adaptation of the carriers of one dose of the tumor suppressor. we studied the patterns of embryonic survival rate of lgl/+ flies under the conditions of competition for life resources ...200717352292
drosophila melanogaster mounts a unique immune response to the rhabdovirus sigma virus.rhabdoviruses are important pathogens of humans, livestock, and plants that are often vectored by insects. rhabdovirus particles have a characteristic bullet shape with a lipid envelope and surface-exposed transmembrane glycoproteins. sigma virus (sigmav) is a member of the rhabdoviridae and is a naturally occurring disease agent of drosophila melanogaster. the infection is maintained in drosophila populations through vertical transmission via germ cells. we report here the nature of the drosoph ...200818378641
pherokine-2 and -3.drosophila is a powerful model system to study the regulatory and effector mechanisms of innate immunity. to identify molecules induced in the course of viral infection in this insect, we have developed a model based on intrathoracic injection of the picorna-like drosophila c virus (dcv). we have used maldi-tof mass spectrometry to compare the hemolymph of dcv infected flies and control flies. by contrast with the strong humoral response triggered by injection of bacteria or fungal spores, we ha ...200312899697
induction of host defence responses by drosophila c virus.insect responses that are specific for virus infection have been investigated using the genetically tractable drosophila melanogaster. most studies focus on interactions with drosophila c virus (dcv), which is a member of the family dicistroviridae. dcv is a non-enveloped, t=3 icosahedral virus with a positive-sense rna genome. it was demonstrated recently that several genes controlled by the jak-stat pathway are specifically upregulated upon dcv infection. to investigate the virus factors that ...200818474566
the polypeptides induced in drosophila cells by drosophila c virus (strain ouarzazate).the ouarzazate strain of drosophila virus (dcv0) was grown in drosophila melanogaster tissue culture cells, and [35s]methionine-labeled virions were found to contain a group of major structural proteins with a molecular weight of approximately 30,000 as well as several minor proteins of higher molecular weight and a protein of approximately 10,000 daltons. using a range of pulses, chases and gel systems, examination of the intracellular proteins induced by dcv0 showed the presence of 17 polypept ...198118635073
the dexd/h-box helicase dicer-2 mediates the induction of antiviral activity in drosophila.drosophila, like other invertebrates and plants, relies mainly on rna interference for its defense against viruses. in flies, viral infection also triggers the expression of many genes. one of the genes induced, vago, encodes a 18-kilodalton cysteine-rich polypeptide. here we provide genetic evidence that the vago gene product controlled viral load in the fat body after infection with drosophila c virus. induction of vago was dependent on the helicase dicer-2. dicer-2 belongs to the same dexd/h- ...200818953338
the genetic architecture of resistance to virus infection in drosophila.variation in susceptibility to infection has a substantial genetic component in natural populations, and it has been argued that selection by pathogens may result in it having a simpler genetic architecture than many other quantitative traits. this is important as models of host-pathogen co-evolution typically assume resistance is controlled by a small number of genes. using the drosophila melanogaster multiparent advanced intercross, we investigated the genetic architecture of resistance to two ...201627460507
infection avoidance behavior: viral exposure reduces the motivation to forage in female drosophila melanogaster.infection avoidance behaviors are the first line of defense against pathogenic encounters. behavioral plasticity in response to internal or external cues of infection can therefore generate potentially significant heterogeneity in infection. we tested whether drosophila melanogaster exhibits infection avoidance behavior, and whether this behavior is modified by prior exposure to drosophila c virus (dcv) and by the risk of dcv encounter. we examined 2 measures of infection avoidance: (1) the moti ...201727362557
addicted? reduced host resistance in populations with defensive symbionts.heritable symbionts that protect their hosts from pathogens have been described in a wide range of insect species. by reducing the incidence or severity of infection, these symbionts have the potential to reduce the strength of selection on genes in the insect genome that increase resistance. therefore, the presence of such symbionts may slow down the evolution of resistance. here we investigated this idea by exposing drosophila melanogaster populations to infection with the pathogenic drosophil ...201627335421
variation and evolution in the glutamine-rich repeat region of drosophila argonaute-2.rna interference pathways mediate biological processes through argonaute-family proteins, which bind small rnas as guides to silence complementary target nucleic acids . in insects and crustaceans argonaute-2 silences viral nucleic acids, and therefore acts as a primary effector of innate antiviral immunity. although the function of the major argonaute-2 domains, which are conserved across most argonaute-family proteins, are known, many invertebrate argonaute-2 homologs contain a glutamine-rich ...201627317784
wolbachia-mediated protection against viruses in the invasive pest drosophila suzukii.the maternally inherited bacterium wolbachia is well known for spreading in natural populations by manipulating the reproduction of its arthropod hosts, but can also have mutualist effects that increase host fitness. in mosquitoes and drosophila some wolbachia strains can lead to an increase in survival of virus-infected insects, and in most cases this is associated with reduced accumulation of the virus in host tissues. we investigated if the wolbachia strain wsuz, which naturally infects droso ...201627144810
impact of erk activation on fly survival and wolbachia-mediated protection during virus infection.elevated levels of reactive oxygen species (ros) provide protection against virus-induced mortality in drosophila. in addition to contributing to oxidative stress, ros are known to activate a number of signalling pathways including the extracellular signal-regulated kinases (erk) signalling cascade. it was recently shown that erk signalling is important for resistance against viral replication and invasion in cultured drosophila cells and the gut epithelium of adult flies. here, using a drosophi ...201626977591
protection of insects against viral infection by apoptosis-dependent phagocytosis.we investigated whether phagocytosis participates in the protection of insects from viral infection using the natural host-virus interaction between drosophila melanogaster and drosophila c virus (dcv). drosophila s2 cells were induced to undergo apoptotic cell death upon dcv infection. however, uv-inactivated virus was unable to cause apoptosis, indicating the need for productive infection for apoptosis induction. s2 cells became susceptible to phagocytosis by hemocyte-derived l(2)mbn cells aft ...201526546607
evolution of drosophila resistance against different pathogens and infection routes entails no detectable maintenance costs.pathogens exert a strong selective pressure on hosts, entailing host adaptation to infection. this adaptation often affects negatively other fitness-related traits. such trade-offs may underlie the maintenance of genetic diversity for pathogen resistance. trade-offs can be tested with experimental evolution of host populations adapting to parasites, using two approaches: (1) measuring changes in immunocompetence in relaxed-selection lines and (2) comparing life-history traits of evolved and cont ...201526496003
drosophila melanogaster does not exhibit a behavioural fever response when infected with drosophila c virus.behavioural fever is a widely conserved response to infection. the host increases body temperature (tb) by altering their preferred temperature (tp), generating a fever and delaying or avoiding pathogen-induced mortality. this response is not ubiquitous in insects, however, although few studies have investigated this response to viral infection. here, we examined the change in tp of drosophila in response to virus infection using a thermal gradient. no difference in tp was observed. we suggest t ...201526408310
sex-specific behavioural symptoms of viral gut infection and wolbachia in drosophila melanogaster.all organisms are infected with a range of symbionts spanning the spectrum of beneficial mutualists to detrimental parasites. the fruit fly drosophila melanogaster is a good example, as both endosymbiotic wolbachia, and pathogenic drosophila c virus (dcv) commonly infect it. while the pathophysiology and immune responses against both symbionts are the focus of intense study, the behavioural effects of these infections have received less attention. here we report sex-specific behavioural response ...201526301521
infectivity of drosophila c virus following oral delivery in drosophila larvae.the route of pathogen entry can have a major effect on the ability of a virus to induce a prolific infection, but it can also affect the ability of the host organism to induce an immune response to fight the infection. transmission of arboviruses that cause serious diseases in humans often begin by an insect ingesting a virus, which then disseminates through the internal organs and tissues and ultimately culminates in virus transmission to a human host. understanding the effect of a natural rout ...201525626683
pelo is required for high efficiency viral replication.viruses hijack host factors for their high speed protein synthesis, but information about these factors is largely unknown. in searching for genes that are involved in viral replication, we carried out a forward genetic screen for drosophila mutants that are more resistant or sensitive to drosophila c virus (dcv) infection-caused death, and found a virus-resistant line in which the expression of pelo gene was deficient. our mechanistic studies excluded the viral resistance of pelo deficient flie ...201424722736
host adaptation to viruses relies on few genes with different cross-resistance properties.host adaptation to one parasite may affect its response to others. however, the genetics of these direct and correlated responses remains poorly studied. the overlap between these responses is instrumental for the understanding of host evolution in multiparasite environments. we determined the genetic and phenotypic changes underlying adaptation of drosophila melanogaster to drosophila c virus (dcv). within 20 generations, flies selected with dcv showed increased survival after dcv infection, bu ...201424711428
involvement of ran in the regulation of phagocytosis against virus infection in s2 cells.phagocytosis plays important roles in innate and adaptive immunity in animals. some small g proteins are found to be related to phagocytosis. however, the ran gtpase has not been intensively characterized in immunity. in this paper, the sequence analysis showed that the ran was highly conserved in animals, suggesting that its function was preserved during animal evolution. the results showed that ran was upregulated in s2 cells in response to dcv infection. it was further revealed that the antiv ...201323916491
physiological and metabolic consequences of viral infection in drosophila melanogaster.an extensively used model system for investigating anti-pathogen defence and innate immunity involves drosophila c virus (dcv) and drosophila melanogaster. while there has been a significant effort to understand infection consequences at molecular and genetic levels, an understanding of fundamental higher-level physiology of this system is lacking. here, we investigate the metabolic rate, locomotory activity, dry mass and water content of adult male flies injected with dcv, measured over the 4 d ...201323685974
wolbachia utilize host actin for efficient maternal transmission in drosophila melanogaster.wolbachia pipientis is a ubiquitous, maternally transmitted bacterium that infects the germline of insect hosts. estimates are that wolbachia infect nearly 40% of insect species on the planet, making it the most prevalent infection on earth. the bacterium, infamous for the reproductive phenotypes it induces in arthropod hosts, has risen to recent prominence due to its use in vector control. wolbachia infection prevents the colonization of vectors by rna viruses, including drosophila c virus and ...201525906062
drosophila mir-956 suppression modulates ectoderm-expressed 4 and inhibits viral replication.small non-coding micrornas (mirnas) can modulate the outcome of virus infection. here we explore the role of mirnas in insect-virus interactions, in vivo, using the natural drosophila melanogaster-drosophila c virus (dcv) model system. comparison of the mirna expression profiles in dcv-infected and uninfected flies showed altered mirna levels due to dcv infection, with the largest change in abundance observed for mir-956-3p. knockout of mir-956 resulted to delayed dcv-induced mortality and decre ...201727960110
gut microbiota in drosophila melanogaster interacts with wolbachia but does not contribute to wolbachia-mediated antiviral protection.animals experience near constant infection with microorganisms. a significant proportion of these microbiota reside in the alimentary tract. there is a growing appreciation for the roles gut microbiota play in host biology. the gut microbiota of insects, for example, have been shown to help the host overcome pathogen infection either through direct competition or indirectly by stimulating host immunity. these defenses may also be supplemented by coinfecting maternally inherited microbes such as ...201727871813
genetics of host-parasite interactions: towards a comprehensive dissection of drosophila resistance to viral infection.one of the major challenges in evolutionary biology is to unravel the genetic basis of adaptation. this issue has been gaining momentum in recent years with the accelerated development of novel genetic and genomic techniques and resources. in this issue of molecular ecology, cogni et al. (2016) address the genetic basis of resistance to two viruses in drosophila melanogaster using a panel of recombinant inbred lines with unprecedented resolution allowing detection of rare alleles and/or alleles ...201627714976
drosophila adaptation to viral infection through defensive symbiont evolution.microbial symbionts can modulate host interactions with biotic and abiotic factors. such interactions may affect the evolutionary trajectories of both host and symbiont. wolbachia protects drosophila melanogaster against several viral infections and the strength of the protection varies between variants of this endosymbiont. since wolbachia is maternally transmitted, its fitness depends on the fitness of its host. therefore, wolbachia populations may be under selection when drosophila is subject ...201627684942
efficient rna virus control in drosophila requires the rna methyltransferase dnmt2.drosophila use small-interfering rna mechanisms to limit the amplification of viral genomes. however, it is unclear how small rna interference components recognize and separate viral from cellular rna. dnmt2 enzymes are highly conserved rna methyltransferases with substrate specificity towards cellular trnas. we report here that dnmt2 is required for efficient innate immune responses in drosophila. dnmt2 mutant flies accumulate increasing levels of drosophila c virus and show activated innate im ...201323370384
interaction between a picornavirus and a wild population ofdrosophila melanogaster.drosophila c virus (dcv) has a considerable impact on ovarian morphogenesis indrosophila melanogaster host populations. this virus also affects the developmental time and the fresh weight of infected females. in order to investigate the hypothesis that dcv may play a role in the dynamics ofdrosophila populations, the fertility and embryonic and larvo-pupal death rates of a host population and that of five dcv-free populations were determined. a comparison of two populations, one of them dcv-free ...198828312425
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